AND DACIAN DUKE HOSPITAL LIBRARY ; / ■ Digitized by the Internet Archive in 2016 with funding from Duke University Libraries https://archive.org/details/pharmacopeiaphys01 hate THE PHARMACOPEIA A Series of Articles which Originally Appeared in the Journal of the American Medical Association, Discussing the Chief Substances in the United States Pharmacopeia, Class- ifying Them According to Their Uses and De- By ROBERT A. HA.TCHER, Ph.G., M.D. Assistant Professor of Pharmacology, Cornell University Medical School, New York and AND scribing Their Methods of Combination and HowThey May Take the Placeof Many Proprietary Preparations for Which Extravagant Claims Have Been Made. MARTIN I. WILBERT, Ph.M., Apothecary to the German Hospital. Philadelphia CHICAGO : AMERICAN MEDICAL ASSOCIATION PRESS 1907 QV 790 . 7 Authority to use for comment the Pharmacopeia of the United States of America, Eighth Decennial Re- vision, IN THIS VOLUME, HAS BEEN GRANTED BY THE BOARD of Trustees of the United States Pharmacopeial Con- vention, which Board of Trustees is in no way respon- sible for the accuracy of any translations of the official weights and measures, or for any statements as to strength of official preparations. duke UNIVERSITY JUIV e Z lyo4 MEDICAL CENTER le.rary Copyright, 1906 , by American Medical Association. \ CONTENTS PAGE Introduction 5 General Disinfectants 18 Sunlight and Heat 19 Chemical Disinfectants 21 Clinical Thermometers and Hypodermic Syringes . 29 Local Disinfectants and Antiseptics 32 Mercurials . . . 43 Antisepsis of the Mucous Membranes 44 Internal Antiseptics 51 General Tonics 70 Hematinics 71 Alteratives 104 Stomachics 118 Astringents 13S Vegetable 143 Metallic 14S Vasoconstrictors 156 Irritants, Emollients and Demulcents 159 Rubefacients 160 Vesicants 173 Pustulants 179 Caustics 180 Emollients 183 Local Anesthetics and Anodynes 188 General Anesthetics 204 Expectorants 219 Sedative 221 Stimulating 227 Demulcent 234 Analgesics and Soporifics 237 Chemistry of Antipyretics 255 Circulatory Stimulants 204 a $ I 5~ CONTENTS. PAGE Circulatory Depressants 297 Diuretics and Diaphoretics 309 Irritants 314 Cathartics 320 Purgative Oils 337 Laxative Sweet Substances 339 Saline Cathartics . . : 341 Parasiticides and Antigonorrheics 353 Anthelmintics 354 Teniafuges 359 Antigonorrheics 365 Substances Used as Vehicles 371 The National Formulary and the Use of Extraphar- macopeal Substances 382 Index 397 THE PHARMACOPEIA AND THE PHYSICIAN. INTRODUCTION. The Pharmacopeia of the United States of America has been the generally accepted authority and the professed guide of American medical men, in matters therapeutic and pharmaceutic, for over eighty-five years. Since the publication of the first edition, in 1820, the book has undergone eight decennial revisions and to-day it is universally conceded to be the peer of authoritative books of its kind, for its scientific accuracy as well as for the general excellence of the descriptions and direc- tions that it contains. This recognized superiority of the Pharmacopeia of the United States of America, in its own par- ticular field, and its generally accepted authority, as a guide, in all matters relating to the strength and purity of the medicinal articles enumerated in its pages, is all the more remarkable in that during its long and varied career it has never been granted a general recognition by statutory enactment. This lack of legal recognition has un- doubtedly been a disadvantage to the book in so far, that, in the past two decades at least, the con- tents and even the very existence of such an au- thoritative book have been largely lost sight of ln- American physicians, and official remedies, to a 6 PHARMACOPEIA AND PHYSICIAN. very marked degree, have been eclipsed or over- shadowed by the innumerable patented and pro- prietary remedies that are constantly brought to the attention of medical men through the advertis- ing material with which their offices are regularly deluged. With a view of bringing the Pharmacopeia itself, its scope and its contents, and particularly the ex- tensiveness as well as the comprehensiveness of the included material, more prominently before the medical profession, it is proposed to present, in the following chapters, a collection of facts and sug- gestions bearing on the number and variety of therapeutic indications that may be fully met with official drugs and preparations. It is also proposed to call attention to the un- reasonable claims and the extraordinary statements that are frequently made in connection with some of the arbitrary combinations of drugs that are offered as proprietary remedies or “patent” medi- cines, and to compare the probable limitations of these self-styled panaceas with the possible applica- tion and the varied uses of the more simple and, therefore, more generally reliable, official remedies, the composition as well as the purity of which can readily be determined by well-known and easily applied methods. That even the most recent, the eighth decennial, revision of the Pharmacopeia can not be said to he free from possible errors of commission and omis- sion must be admitted, but many of the shortcom- ings of the book are really due to the general lack INTRODUCTION. of interest that has been displayed by physicians ; and many, if not all, of these shortcomings should be corrected in future revisions, if members of the medical profession would but make their needs and wishes known at the proper time and place. It has been repeatedly asserted that the Pharma- copeia of the United States, as such, is designed primarily for pharmacists and for the manufac- turers of pharmaceutical galenicals, and that it contains little or nothing of direct interest to the physician. One of the prime objects of the follow- ing chapters will be to demonstrate that this asser- tion embodies only a half truth and that the present edition of our national Pharmacopeia really con- tains much that does, or at least should, interest every medical practitioner in the land. In this connection it should also be remembered that the technical descriptions and tests for which the average physician may think he has little or no use, are in reality essential to secure for him, and through him for his patients, remedies that are not only reliable, but which are also uniformly active. As an introductory to this work, it may be per- missible to give a brief review of the history of our national Pharmacopeia and incidentally to call attention to some of the various causes that have led up to the present widespread use of proprietary medicines and nostrums. To do this it will be necessary to call attention to some of the short- comings of our Pharmacopeia, from a medical point of view, and to refer to at least several of the 8 PHARMACOPEIA AX O PHYSICIAN. attempts that have been made to correct these shortcomings by offering either a substitute book or by introducing more or less radical changes in ' the book itself. During the colonial period, and even during the first three decades of the independence of the United States the pharmacopeias, or the dispensa- tories that were based on the pharmacopeias of Edinburgh, London and Dublin, in the order given, were practically the only authoritative books on materia mediea known in this country. A rather notable exception is to be found in the small pamphlet, of 32 duodecimo pages, containing 100 titles, that was published as “A Pharmacopeia for the use of the Military Hospital belonging to the Army of the United States,” during the Kevo- lutionary period. The first edition of this little book was published in 1778 and a second edition, bearing the name of Dr. William Brown as editor, was printed in 1781. The earliest known attempt to produce a dis- tinctly representative American Pharmacopeia was made by the members of the College of Physi- cians of Philadelphia, who, on .June 1. 1788. ap- pointed a committee of eight members to form a pharmacopeia for the use of the college. The mem- bers of this committee, being desirous “that the work should be accommodated to the practice of medicine throughout the United States," contin- ued the preliminary work and correspondence for over ten years, but finally allowed the project to languish. INTRODUCTION. 9 Recognizing the need for a more distinctly American book. Dr. J. Redman Cose, of the Uni- versity of Pennsylvania, in 1806, published what was practically a reprint of Duncan’s Edinburgh Dispensatory, under the title of “The American Dispensatory.” The nest American publication, in point of time, was the Pharmacopeia of the Massachusetts Medical Society, published in 1808, and this was followed in 1810 by Dr. James Thach- er’s American New Dispensatory, also published in Boston. These books supplied two of the then esisting medical centers, and the territory more or less dependent on them, with reference books on materia medica, of American origin. The territory more directly dependent on New York City was, in a measure, supplied by the publication of “The Pharmacopeia of the New York Hospital.” in 1816, and the subsequent publication, in 1818. of an American reprint of the Edinburgh New Dis- pensatory. This rapid multiplication of authori- tative books appears to have been unsatisfactory and no doubt led to the revival of the project, pro- posed many years before, of forming a truly na- tional pharmacopeia. American physicians, and particularly the lead- ers in American medicine, have contributed so lit- tle to the evolution or advancement of the Pharma- copeia of the United States of America, during re- cent decades, that, no doubt, it will be interesting, if not surprising, to many, to be reminded of the fact that the inception as well as the inauguration of the Pharmacopeia is to be accredited to the lead- 10 PHARMACOPEIA AND PHYSICIAN. ing minds in the medical profession of this coun- try, eighty or more years ago. It was at a meeting of the Yew York County Medical Society, in Janu- ary, 1817, that Lyman Spalding suggested the first practicable plan for securing a national pharma- copeia. At the annual meeting of the Medical So- ciety of the State of Yew York, held at Albany, in February, 1817, the same plan was discussed and a committee was appointed to consider the necessary details and to report at the next annual meeting. The report of this committee being in favor of the proposed plan, the society, in 1818, appointed dele- gates to meet in district convention, for the pur- pose of forming a pharmacopeia. Of the mem- bers of the Yew York State Medical Society who took an active part in forming this first national pharmacopeia it may be well to mention the names of Lyman Spalding, Samuel L. Mitchill, David Hosack, Valentine Mott, T. Korneyn Beck. Wright Post and Alexander H. Stevens. Other members of the profession were hardly less enthusiastic. In Boston the proposed plan received the earnest sup- port of John C. Warren, Jacob Bigelow, James Thacher and George C. Shattuck. In Yew Haven it was endorsed by Eli Ives, William Tully and Yathan Smith; in Baltimore by Elisha DeButts, Samuel Baker and Yathaniel Potter, while in Philadelphia, Thomas T. Hewson, Samuel P. Grif- fiths, Thomas C. James, Edwin A. Atlee and Joseph Parrish, all of them active and influential members of the College of Physicians, gave the plan their unqualified support and endorsement. INTRODUCTION. 11 On Jan. 1, 1820, the first General Medical Con- vention was convened at the Capitol, in the City of Washington, for the purpose of preparing and publishing a national pharmacopeia. The conven- tion was organized by electing Samuel L. Mitchill, New York, president, and Thomas T. Hewson, Philadelphia, secretary. The necessary details connected with the preparing, publishing and edit- ing of the proposed pharmacopeia were entrusted to a committee composed of Drs. Lyman Spalding, Thomas T. Hewson, Eli Ives, Elisha DeButts and Jacob Bigelow. The copyright of “The Pharma- copeia of the United States of America was sub- sequently sold to Charles Ewer, of Boston, “for a large sum” and the book was finally published un- der date of “Dec., 1820.’' This completed pharmacopeia, although pre- pared and edited by a committee of the most promi- nent medical men of the day, and printed in Latin, as well as in English, was soon found to be “in its nature too circumscribed and technical” for the use of physicians. To overcome this objectionable feature and to popularize the book and its contents with medical practitioners. Dr. Jacob Bigelow, a well-known medical writer and one of the editors of this first national pharmacopeia, in 1822, published what he was pleased to term “A Treatise on the Materia Medica, Intended as a Sequel to the Pharmacopeia of the United States, Being an Account of the Origin, Qualities and Medical Uses of the Articles and Compounds which Constitute that Work, with 12 PHARMACOPEIA AYE) PHYSIC I A X. Their Modes of Prescription and Administration.” This book, practically a pharmacopeia for physi- cians, appears to have met with considerable popu- larity, and the well-worn pages of the still existing copies of the book certainly bear evidence to the fact that they were frequently consulted. That a pharmacopeia, consisting largely of a simple enumeration of drugs with detailed direc- tions for the several medicinal preparations, could not be expected to appeal to the medical profes- sion, and that, unless such a book were well known to the individual members of that profession, it would have little or no reasonable excuse for its existence, appears to have been clearly appreciated by the members of the medical convention that met in the city of New York in January, 1830, for the purpose of revising the Pharmacopeia. The members of this convention decided to, and subsequently did, introduce several really novel features into this first revision that are only now. three-quarters of a century after the publication of the book, being revived and discussed. In addition to having short descriptions of the physical proper- ties of drugs, both whole and powdered, this Phar- macopeia also included doses, and, what is even more, also included short, suggestive remarks on the “Medicinal Operations” or therapeutic prop- erties of the several drugs that were included in the text. For some unknown, and certainly unforeseen, reason there appears to have been a misunderstand- ing in regard to the method of electing delegates INTRODUCTION' . 13 to attend the General Medical Convention and at least a portion of the delegates from the Middle States did not attend the convention in New York, but decided to hold a convention of their own in the city of Washington. As a direct outcome of this opposition convention we have another, “first” revision of the national Pharmacopeia, published in Philadelphia in 1831. This 1830, Philadelphia revision of the na- tional Pharmacopeia, as it is generally known, was continued along practically the same lines as the original pharmacopeia published in Boston in 1820 and did not appear to meet with the use and sale among physicians that its authors expected. To popularize this edition of the pharmacopeia, and also to furnish American medical practition- ers with a convenient handbook on therapeutics, two of the younger members of the committee on revision, Drs. George B. Wood and Franklin Bache, decided to prepare and to publish a com- mentary on the national Pharmacopeia. This book, known as the “Dispensatory of the United States of America,” first published in 1833, met with instantaneous and really phenomenal success. Three editions were sent to press within as many years and the book rapidly displaced the Pharmaco- peia itself with both physicians and apothecaries, and led to the rather anomalous condition of hav- ing a commentary that was generally accepted as being more popular and, therefore, more important than the Pharmacopeia itself. For more than fifty years the Pharmacopeia 14 PHARMACOPEIA AND PHYSICIAN. occupied such a secondary and comparatively un- important position to the Dispensatory that it was generally asserted that it would be practically im- possible to have the Pharmacopeia published apart from the Dispensatory. Fortunately the authors of the Dispensatory were men of exceptionally high ideals and for over fifty years were the lead- ing contributors to the advance and progress of the Pharmacopeia itself. That the unrelenting hand of time brings changes that stay progress was evidenced in 1876, when Dr. E. P. Squibb, of Brooklyn, called the attention of the members of the American Medical Association to the fact that the then official Phar- macopeia could not be said to represent the existing status of the practice of medicine and pharmacy. Dr. Squibb also pointed out that, owing no doubt to the death of one of the editors of the United States Dispensatory, Dr. Franklin Bache, and the very advanced age and practical retirement of Dr. George B. Wood, that book had not been carefully revised, or brought up to date, and, therefore, that the medical profession was entirely devoid of any authoritative work on materia medica and phar- macy. To overcome the evident stagnation that had crept into the revision of the national Pharmaco- peia, at that time, Dr. Squibb proposed that future revisions be undertaken by, and conducted under the supervision of, the American Medical Associa- tion. This latter proposition met with such active and bitter opposition, however, that in 1S77 fur- INTRODUCTION. 15 ther consideration of this project was indefinitely postponed. During the decade immediately following this discussion, there arose a number of additional fac- tors to detract from the popularity and from the general use of the national Pharmacopeia. Xot the least of these is to be found in the innovations that were included in the 1880 (sixth decennial) revision of the Pharmacopeia itself. This is a sub- ject that is more of pharmaceutic than therapeutic interest, however, and its further consideration may be omitted at this time. One other factor, and not by any means an un- important one from an economic point of view, was the introduction of German synthetic chemi- cals, and the accompanying scramble for publicity by ambitious, professedly progressive medical prac- titioners in the reading pages of our medical journals. Tvairin, the first of these synthetic products to reach us, was introduced in 1883, and soon proved to be not only unreliable, but positively dangerous. It was followed, in 1884, by antipyrin, which met with phenomenal use and added untold wealth to the coffers of the manufacturer. The commercial success of this substance stimulated others to re- newed activity, and in the succeeding years Ameri- can plrysicians were deluged by a number of really useful, as well as some positively dangerous, syn- thetic remedies, to say nothing of the many hun- dreds of' elegant pharmaceuticals, all of them lauded and exploited as new remedies. 16 PHARMACOPEIA. AXD PHY8ICIAX. This rapid accumulation of true, as well as of pseudo, new remedies appears to have had a stimu- lating effect on the editors of the several dispensa- tories and text-books on materia medica and thera- peutics. These hooks grew rapidly in size and in the variety of the contained material until the official or pharmac-opeial portion was lost in the superabundance of wonderful cures and remedies that were offered for the alleviation of the ill- and ailments of the human family. Added to all this plethora of new remedies a feeling of therapeutic- nihilism developed until it was quite proper for a physician to disclaim all knowledge of the use of drugs and boldly to assert that he was entirely independent of the necessity for such really anti- quated measures as drug therapy. The publication of the 1890, or seventh decen- nial revision, of the national Pharmacopeia offered or suggested but little change in the then existing conditions other than to reintroduce the long-es- tablished English practice of measuring liquids and weighing solids. Even this concession did not appear to have the desired effect of popularizing the Pharmacopeia. This no doubt was due largely to the fact that pharmacists are proverbially slow in adopting new ideas, and physicians are even slower, Or are loth, to insist on rational innovations being adopted wherever practicable. With the advent of .the new century, there ap- pears to have been a re-awakening on the part of the members of the medical profession, at least, INTRODUCTION . 17 and the interest that has been manifested in the work of the Council on Pharmacy and Chemistry of the American Medical Association, the articles that have appeared in lay journals on the abuse of nostrums by the laity and, last but no means least, the comments that have appeared in medical journals on the contents of, and the changes that have been made in, the recently issued eighth de- cennial revision of the Pharmacopeia of the TJ nited States of America all bear evidence to the existence of a healthy spirit of inquiry among medical prac- titioners in this country. As previously noted, it is our present purpose to foster and aid this spirit of inquiry and to pre- sent what, at times, may perhaps seem elementary and well-known facts. If we succeed in making many members of the medical profession more familiar with the drugs .and preparations which are included in our national Pharmacopeia, we shall feel that we are well repaid for our efforts. CHAPTER I. GENERAL DISINFECTANTS. The important subject of antisepsis embraces so many different agents that are used in such a va- riety of conditions that any convenient considera- tion of them according to their uses, or according to the principles that are involved, must neces- sarily be an arbitrary one. For our purpose we shall consider them under three heads: (1) Gen- eral disinfectants and antiseptics; (2) local disin- fectants and antiseptics, and (3) internal antisep- tics. Some substances will require consideration under all three headings, but even this will be found preferable to giving, for example, all of the manifold uses of such an article as mercuric chlo- rid in one place. Antiseptics were used long before the causes of fermentation or of putrefaction were known, and it would have been remarkable indeed had man failed to perceive the effect of those substances which are capable of inhibiting a process so com- monly encountered. The Egyptians preserved the human body against the attacks of putrefactive organisms, without any evident knowledge of the character of the organisms causing decay, by means of balsams which contained such antiseptics as ben- zoic and cinnamic acids. The epoch-making dis- coveries of Pasteur, followed, as the} 7 were, by the DISIXFECTAXT.S. 19 favorable reports on the use of phenol, or carbolic acid, by Lister, and the subsequent discovery that other substances possessing great antiseptic power were even less toxic to man, gave tremendous force to the pendulum, which was carried entirely too far by the efforts of well-meaning enthusiasts, and in its backward swing much unnecessary skepticism has been aroused. While the subject of general disinfection does not necessarily form a part of the physician’s daily consideration, there are occasions when he is sud- denly confronted with the necessity of directing such work, and on the thoroughness with which he does it will depend the safety of other members of the community. While there is no great difficulty in securing thorough disinfection, it is absolutely necessarv that certain rules be rigidly complied with and this can not be done without an exact knowledge of the object that is to be accomplished and of the means with which the accomplishment is to be brought about. There is probably no con- dition where a little knowledge can prove to be more dangerous than in this very matter of dis- infection, and we therefore have no apologies to offer for going into details on a subject that may be considered commonplace or well understood. SUNLIGHT AND HEAT. The best of all disinfectants is bright, direct sunlight, coming into immediate contact with the individual germs, not merely shining on one side of a thick garment or carpet, or on small masses of sputum, blood, pus or decaying meat, but shining- on, and penetrating, each individual micro-organ- ism. When this can be accomplished all germs — - 20 PHARMACOPEIA AND PHYSICIAN. not all spores — are killed in a few hours. But sunlight is not dependable unless all of the neces- sary conditions can be rigidly complied with, as may be done with impervious flat surfaces (floors), or linen and other thin garments, both sides of which may be exposed to the direct rays of the sun. The disinfection of articles infected with the more virulent pathogenic organisms usually re- quires other, more directly active, means than that of sunlight, with the attendant danger of further dissemination, and chemic disinfectants or heat must then be employed. The direct flame instantly destroys all forms of microscopic life. Dry air, heated to 160° C. (320° F.), kills all disease germs — but not all spores— in one hour; but wood will begin to char at 180° C. (356° F.) and even lower, so that dry hot air is not applicable as a certain means of disinfection in all cases. Simple drying kills bacteria; but masses of sputum or other organic matter may pre- serve the organisms in the interior for an indefinite period, while spores are thus preserved for years. Moist heat, water or air saturated with aqueous vapor, heated to 75° C. (167° F.), is rapidly fatal to most bacteria. Water containing typhoid bacilli is rendered much safer by heating to even this comparatively low temperature for ten minutes. Boiling water, on the other hand, will kill even spores in ten minutes or more if they are not pro- tected in small masses. When such masses do exist 1 per cent, of soda or soap should be added to the water to dissolve the albuminous and other organic matter and at the same time to raise the boiling point slightly. Metallic instruments do not rust DISINFECTANTS. 21 m water containing caustic soda, washing soda, baking soda or boras. Moist steam, or air which is supersaturated with steam, is rapidly fatal, but superheated dry steam is not so quickly fatal as is the moist at a much lower temperature. Pressure, moisture and in- creased temperature increase the effectiveness of all methods of disinfection. Moist steam penetrates better than dry air, but heavy fabrics may protect micro-organisms, and particularly spores, for a considerable time, and many articles, such as mat- tresses, can not be readily disinfected even in this way. CHEMICAL DISINFECTANTS. Bedrooms and their contents may be disinfected by the now official : Liquor Formaldehydi. — U. S. — Solution of Formaldehyd, containing about 37 per cent, by weight of formic aldehyd, an osyclation product of methyl alcohol. This substance may be applied directly by washing or spraying, or it may be used in the form of vapor. For the latter purpose the windows and doors are tightly closed, paper being used to stop up the crevices, carpets should be re- moved or suspended and all drawers and closets opened and their contents so placed that the vapor will readily reach and penetrate every particle of fabric. Formaldehyd solution is then vaporized either in the room or through the keyhole with enough water to saturate the air in the room. Con- siderable loss of formaldehyd occurs through de- composition during vaporization by heat, and it is, therefore, preferable to saturate sheets with the requisite quantity and suspend them in the room 22 PHARMACOPEIA AND PHYSICIAN. which is to be disinfected, or, better still, the solu- tion may be sprayed from an atomizer. The key- hole is then plugged and the room allowed to stand for from 12 to 24 hours. iSTovy advises 150 c.e. (5 fl. oz.) of the 40 per cent, solution, correspond- ing to about 165 c.c. (5% A- oz.) of the official, for each 1,000 cubic feet of air space. To increase the efficiency of the formaldehyd, 3 liters (3 quarts) of water are vaporized into each 1,000 cubic feet of space. If the atmosphere is damp, less water will be required, of course. Under ordinary conditions it is cheaper to destroy inexpensive mattresses than to disinfect them thoroughly. If they are of straw, destruction is more readily accomplished by burn- ing them out of doors. Calx. — U. S. — Lime, calcium oxid. constitutes an inexpensive and very useful disinfectant that has a number of widely varying uses. Infected urine, vomit and feces may be thoroughly disin- fected by being received into a vessel that contains freshly prepared milk of lime. It is essential that this be freshly prepared, as calcium hydrate rapid- ly absorbs carbon dioxid from the air and is there- in’ changed into the inactive calcium carbonate. Milk of lime may be prepared by putting a few pounds of lime into an iron pot and adding about half as much water; the lime rapidly falls into a dry powder with the evolution of heat : to this pow- der add three times as much water and stir well. The resulting mixture will keep for several days without deteriorating sufficiently to be inert. There are, of course, several precautions to be observed: The lime must be recently calcined, or fresh, and the person who slakes it should be careful to avoid the irritant dust which arises during the process; DISINFECTANTS. 23 then, too, the heat generated may be sufficiently high to char wood or to set fire to readily combusti- ble materials. For disinfecting feces or other substances they should be thoroughly stirred with an equal quantity of the milk of lime, or, better still, with twice the quantity, the mixture being allowed to stand for two hours. Milk of lime is also useful for disinfecting floors, cellars, cesspools after draining, and even walls when they are not subject to injury. It must al- ways be remembered that this whitewash rapidly absorbs carbon dioxid and thus becomes inert, hence the mixture is an efficient disinfectant, but is not useful as an antiseptic. Unslaked lime is a cheap and very efficient means of destroying animal matter and is also useful for absorbing moisture in damp cellars. As noted before, certain precautions are always to be taken in connection with this realty active chemical sub- stance. Cesspools are difficult to disinfect. Large quantities of milk of lime are effective, but the con- tents must be thoroughly mixed with the disin- fectant, whatever its nature. Hydrargyri Chlortdum Corrosiyttm.- — IT. S. — Corrosive Mercuric Chlorid. bichlorid of mer- cury, mercuric chlorid, or, as it is most commonly called, corrosive sublimate, will be considered more extensively in connection with local antiseptics. It has, however, a number of very important uses in connection with disinfectants. Corpses of persons dead of an infectious disease should be immediately wrapped in cloths saturated with a 1 to 1.000 solution of mercuric chlorid. The addition of 20 per cent, of glycerin to the solution of mercuric chlorid will prevent the rapid evapora- 24 PHARMACOPEIA AND PHYSICIAN. tion of the water, which leaves the mercuric chlorid as a dry powder in the cloth. Water which has been used to bathe a person suffering from an in- fectious disease, such as typhoid fever, should be disinfected by heating to near the boiling point or by the addition of a liberal quantity of milk of lime or a much smaller quantity of mercuric chlo- rid. If the bathtub is of metal, the latter chemical should not be used, but phenol or cresol may be substituted. Ferri Sulphas. — IT. S. — Ferrous Sulphate, preferably the impure or crude article, commonly called copperas, is an excellent deodorizer for ani- mal excretions, the iron uniting with the albumin and the acid with the ammonia; it is not a very active disinfectant. Cupri Sulphas. — IT. S. — Copper Sulphate, or blue vitriol, may be similarly used, but it is much more expensive and possesses no marked advan- tages over copperas as a deodorizer. Sulphur Sublimatum. — IT. S. — Sublimed Sulphur, or flowers of sulphur, is frequently burned as a disinfectant, in rooms which contain nothing which can be injured by the corrosive ac- tion of the resulting sulphurous oxid. It is not so frequently used now that formaldehyd affords a more satisfactory means of disinfection, but it is cheaper and may be used to advantage in cellars and in empty rooms, that can be thoroughly sealed. Hoppe-Seyler recommends that 15 gm. (Vo oz.) be burned for every cubic meter (cubic yard) of space. This would be equivalent to about 450 gm. (15 oz.) for 1,000 cubic feet. Rooms should be left tightly closed for from twenty-four to forty- disinfected by heating to near the boiling point or DISINFECTANTS. 25 may be readily absorbed by sprinkling ammonia in the room. As with formaldeliyd disinfection, the vapor must come into actual contact with the mi- cro-organisms and the atmosphere should contain moisture. This latter requirement is usually met by burning the sulphur in a double vessel, the outer one containing water. The gas that is generated by the burning of sul- phur is very poisonous to man, due to its local cor- rosive action. Spasmodic closure of the glottis may occur, causing death. Sulphurous oxid, the substance that is thus generated, remains free in mixtures of organic matter longer than free chlo- rin. hence it is a more effective bactericide. Calx Chlorinata. — U. S. — Chlorinated Lime, popularly, though improperly, called chlorid of lime, is a ready source of chlorin and is a very con- verdent and inexpensive disinfectant suitable for many of the purposes for which sulphurous oxid might be used. Chlorin. like sulphurous oxid, is very corrosive, attacking metals, and bleaching and destroying fabrics. Chlorinated lime is useful for sprinkling about urinals, damp cellars, out- houses, stables and drain*. It rapidly deteriorates on exposure to the air and only tightly sealed packages from reliable firms should be used. The various solutions of clilorids that are sold at fancjr prices are usually feeble and are in nowise superior to a readily made mixture of a quarter of a pound of chlorinated lime with half a gallon of water. The admixture of an acid at the time of using causes the rapid liberation of chlorin and in- creases the disinfectant action. Liquor Sod^: Chlorinat2e. — IJ. S. — Solution of Chlorinated Soda, the so-called Labarraque’s 26 PHARMACOPEIA AND PHYSICIAN. solution;, is but another form of a chlorin com- pound. It has the one advantage of being free from insoluble caustic material. 1 Phenol. — U. S. — Phenol, the Acidum Car- bolicum of the TJ. S. P. 1890, is much more ex- pensive and not nearly so efficient, as a disinfect- ant. as: Cresol. — IT. S. — Cresol has been included in place of the formerly official crude carbolic acid. It is a mixture of the three isomeric cresols, found in coal tar, and is a useful and highly efficient disinfectant and antiseptic. Liquor Cresolis Compositus. — U. S. — Com- pound Solution of Cresol consists of a mixture of equal parts of soap and cresol. When properly made this mixture is an admirable substitute for any one of the numerous soluble or semi-soluble proprietary preparations containing cresol : such as creolin, cresolin, lysol, lysitol and a host of others too numerous to mention. Compound solution of cresol is practically iden- tical with the Liquor Cresoli Saponatus of the German Pharmacopeia; it is miscible in all pro- portions with water, and, as noted before, is a re- liable and readily available disinfectant. 1. Where an inodorous deodorant is required it 'will be found that the Liquor Zinci et Alumini Compositus of the National Formulary will give better and more uniform satis- faction than proprietary articles of the same type. It is made as follows : R. Zinci sulphatis Alumini sulphatis, aa Sxxyii 100 Naphthol gr. v 3 Olei thymi gr. xv 1 Aqu®, q. s. ad Oi 500 The salts are dissolved with the aid of heat and the vol- atile substances added to the solution. Still another preparation of the same type is the Liquor Zinci et Ferri Compositus — N. F. DISINFECTANTS. One part of the compound solution of cresol added to twenty parts of very warm water is useful for the sterilization of surgical instruments, and a slightly weaker solution, made by adding one part to thirty of warm water, affords an excellent disin- fectant for the hands. Potassii Permanganas. — IT. S. — Potassium Permanganate attacks all forms of organic matter and is generally useful for the destruction of foul odors, but is not very useful as a disinfectant. It will be considered later at greater length. The strong mineral acids are destructive to bac- teria, but their application as disinfectants is necessarily very limited. As noted before, mercuric clilorid is to be classed with the most powerful of all disinfectants in general use, one part in 10,000 being fatal to spores. ' Like all other chemical disinfectants, its activity is increased by heat. It precipitates albumin and its efficiency is, therefore, materially lessened by the presence of any appreciable amount of such organic material ; this disadvantage of mercuric chlorid may be ob- viated in part by the addition of an equal amount of sodium or ammonium chlorid (or a small amount of hydrochloric acid), the tablets found on the market for preparing the solutions always containing the requisite quantity of one of those salts. As it attacks metals, it is not suited for the disinfection of instruments or metallic vessels. One part of mercuric chlorid in 50.000 parts of water has been demonstrated to possess decidedly anti- septic properties. Its comparative non-volatility, its property of attacking metals and of combining with albumin, and its extreme toxicity limit its 28 PHARMACOPEIA AST) PHY PIC I AX. field of application, but it remains by far the cheap- est antiseptic we have for general use. Copper sulphate shares with copperas (crude ferrous sulphate) the power of deodorizing decom- posing organic matter, though it is but little used for this purpose. It has recently been claimed that the merest trace of copper sulphate, or of copper, in water readily destroys the bacillus of typhoid fever, or at least completely inhibits its growth; even though the copper is present in quantities too small to interfere with the use of the water for drinking. The results of different investigators are not uniform, however, and some maintain that the antiseptic power of copper and its salts has been greatly overestimated. The soluble salts of zinc, particularly the chlorid, have also been used for disinfecting purposes, but as they share with copper the disadvantage of being comparatively expensive, without any accompanying material ad- vantages, a more detailed consideration of these substances may be omitted in this connection 2 CLINICAL THERMOMETERS AND HYPODERMIC SYRINGES. The disinfection or sterilization of clinical ther- mometers and of hypodermic syringes and needles 2. The' following quotation, taken from Wood's “Thera- peutics,” page 823, contains suggestions that are of interest in this connection. “There are not many affairs in life in which the public has been so super-abundantly fleeced as in the matter of disinfection. A most extraordinary part of this swindling is the ease with which distinguished members of the medical profession have given certificates of efficiency and value to comparatively inert and extraordinarily expen- sive proprietary compounds. . Oddly enough, the cat that has drawn the chestnuts out of the fire for avaricious manufac- turers has not even had the sense to smell the odor of its own paws when burning.” It is evident that Dr. Wood knew less of the resources and the wiles of nostrum makers, and their shrewdness in duping physicians, than he supposed, else he would not think it extraordinary that so many have been deceived. DISINFECTANTS. 29 deserves especial mention. With the present com- paratively low price of clinical thermometers there is little or no excuse for not having an individual thermometer for each patient ill with an infec- tious or a contagious disease or a continued fever. But, even this precaution, desirable as it certainly is, does not obviate the necessity for disinfecting or sterilizing the thermometer. The necessary dis- infection may he effected in a number of ways, the thermometer may be dipped for a few minutes in strong phenol, the solution of cresol, or in the now official solution of formaldehyd, after which it is thoroughly rinsed in water. Where an individual thermometer is provided it may be sterilized by keeping the bulb immersed in 75 per cent, alcohol, a saturated solution of boric acid, the official liquor antiseptic-us. or in a mixture of equal parts of antiseptic solution and of solution of hydrogen dioxid. It must appear even to the least careful that the disinfection of clinical thermometers is a precaution so important that it should never be neglected. The hypodermic syringe and needle should he disinfected with strong phenol or cresol solutions, solution of formaldehyd or by repeated washing with very hot water, as a purely routine procedure, When a syringe and needle are known to be in- fected the disinfection should be as thorough as that of other surgical instruments. Solutions intended for hypodermic injection can be sterilized by boiling, when this does not cause decomposition. With the now widely used hypodermic tablets it is preferable to boil the nec- essary quantity of water, or, better, distilled wafer, for a minute or two, then add the tablet, avoiding 30 PHARMACOPEIA AND PHYSICIAN. all 'unnecessary handling, and heat sufficiently to insure thorough solution. Cocain, being readily decomposed, can not be boiled, but the solution may be sterilized by heating to about 80° C. (176° F.) for thirty minutes on two successive days. It will usually be found to be preferable, however, to use freshly prepared solutions that have been made in a sterile bottle with recently boiled and sterile distilled water. Eucain and stovain solutions may be boiled, but these substances themselves are not entirely free from objections. Under the subject of internal antiseptics we shall have occasion to mention the disadvantages of sterilized milk, but here we may call attention to the widespread use of formaldehyd, salicylic acid and other chemical antiseptics for the pres- ervation of foods. While we are far from being cer- tain that minute quantities of many of these chemi- cal antiseptics are in themselves injurious, we have ample authority for the opinion that their contin- ued use in appreciable quantities is by no means beneficial. Schmiedeberg regards the constant use of even small quantities of salicylic acid, for a con- tinued period, as unwise in the present state of our knowledge, and Sollmann says that the use of formaldehyd can not be too strongly condemned, because of the specific irritation of the mucous membranes which it causes. The whole subject of food preservatives, how- ever, while of vital importance, is one in which the physician should, and indeed must, be actively in- terested, but it is entirely too extensive to be dis- cussed at length here. The subject of preservatives, however, is also of interest in connection with medicines and medici- DISINFECTANTS. 31 nal preparations. The antiseptic action of alcohol, glycerin, sugar and of volatile oils is well known and generally recognized, and, while not of suffi- cient importance to lie considered in connection with general disinfection, these substances are widely used as preservatives not alone for medici- nal preparations and foods, but also for other sub- stances and materials. The use, or abuse, of pres- ervatives in connection with medicinal prepara- tions, particularly in connection with proprietary remedies, is a matter that is deserving of more at- tention than is now being accorded it; as the presence of preservatives may, and undoubtedly does, influence the physiologic action of other in- gredients. CHAPTER II. LOCAL DISINFECTANTS AND ANTISEP- TICS. Lister’s use of local antiseptics in surger} r is usually spoken of as a discovery, but, without de- tracting in any way from the credit due to Lister, it should be referred to more correctly as a prac- tical application of previous discoveries. Reichenbach, in 1832, obtained a substance from wood tar which he named creosote. Finding later that it consisted of phenol and phenol ethers, and also finding these same substances in smoke, he concluded, and later conclusively proved, that to them is due the meat preserving activity of smoke. Runge, in 1834, found that the phenol which he obtained from coal tar also possessed the power of preventing putrefaction. Tar and a number of products of a similar nature were long ago rec- ommended and widel}’ used for foul smelling ul- cers, but the fact remains that to Lister is univer- sally. and very properly, accorded the distinction of having placed antisepsis in surgery on a sure basis. Since the early days of antisepsis there have been many improvements, and we now know that the most perfect cleanliness, or asepsis, that is attainable is much to be preferred even to the most elaborate antisepsis. It is, of course, entirely beyond the scope of this treatise to consider the details of major surg- ery, but the principles of antisepsis which obtain in this branch are equally applicable to minor operations, and their disregard by many, who are LOCAL ANTISEPTICS. 33 not surgeons, is the best justification for their present brief consideration. The necessity for scrupulous cleanliness is seen in such a common, but admittedly important, procedure as vaccin- ation. The careful physician will perform even this simple operation under aseptic conditions, thereby saving himself much annoyance in case of accident. The first, and really the most important, duty of the physician with regard to infections is to see that he does not carry them to other patients. There can be no doubt that physicians have played no small part in the spread of infectious diseases, particularly in the past, but fortunately, with the better understanding of the subject, this seldom occurs now. The disinfection of clothing and of instruments belongs to the subject of general disinfection, that of the hands and person to local disinfection. The cleansing of the hands, as it is done in a number of American hospitals, is about as fol- lows : “Trim and clean the nails, wash the hands and forearms for five minutes in very warm, sterile water, using green soap and scrubbing them energetically with a brush or a gauze pad, cleansing the nails again during this part of the process. Rinse the hands for three minutes in 75 per cent, alcohol, to remove soap and to aid in sterilization ; then in 1 to 1,000 solution of mer- curic chlorid, or in a solution of 1 to 2,000 mer- curic chlorid with 1 to 40 phenol, and finally rinse in sterile, warm water.” This may be some- what more elaborate than is necessary in most cases of minor surgery, but even here it is well to err on the safe side. 34 PHARMACOPEIA AND PHYSICIAN. For the disinfection of the whole body a full bath in warm water with the liberal and judicious use of soap is sufficient, and the clothes may undergo disinfection separately at the same time. This procedure is so simple that the physician can not escape blame should he carry infection from one patient to another through the omission of necessary precautions. When minor surgical operations are to be per- formed it is always well to thoroughly disinfect the surface at and around the prospective seat of operation. For this purpose the procedure given for cleansing the hands of the surgeon is sufficient, though in some cases it may be found necessary to supplement the soap and water with oil of turpentine. Wounds and ulcers require disinfection to de- stroy those bacteria which can be reached, and antiseptic dressings to prevent the development of colonies from those which escape destruction or which may afterward reach the spot. Aqua Hydrogenii Dioxide — TJ. S. — Solution of Hydrogen Dioxid, or, as it is frequently called, Solution of Hydrogen Peroxid, is useful for de- composing pus, in which bacteria are protected from the action of other disinfectants. It thus secures the rapid cleansing of freely exposed pus cavities or ulcers, and at the same time it acts powerfully on bacteria, though they are not all destroyed so long as any pus remains. The offi- cial solution is equal, in disinfectant power, to a 1 to 1,000 solution of mercuric chlorid. The ac- tion on pus of hydrogen dioxid is so extremely rapid that it frequently detaches small masses which may escape decomposition. LOCAL ANTISEPTICS. 35 The use of this solution is not unattended with risks, particularly in sinuses or deep, partially closed wounds. Mucous membranes decompose hydrogen dioxicl rapidly, and the skin slowly, with the liberation of nascent oxygen. It is not certain whether the bactericidal property is due to the liberation of oxygen alone, or whether the prepara- tion possess a special influence on the micro-organ- isms. The decomposition whereby the oxygen is liberated is supposed to depend on a ferment, catalase, which is widely distributed, and, as the preparation loses its bactericidal powers, once the oxygen has been liberated, it is of course useless as an antiseptic, though extremely -useful as a disinfectant. Hydrogen dioxid has an especial reputation in the treatment of sore throat and even diphtheria, for which it is used as a spray, or as a gargle with entire safety. It attacks met- als readily, and only rubber or glass should be used in connection with it. Diluted with an equal amount of water, it is an excellent mouth wash, but not infrequently contains a little acid, and the mouth should be rinsed after its use . 1 After the disinfection of ulcers and wounds an antiseptic dressing is applied. -Cotton, gauze and lint impregnated with various antiseptics are found on the market. Only the active substances that are used iu this connection will be discussed, as the application of dressings belongs to surgery. Iodoformum. — U. S. — Iodoform, Tri-iodome- thane is usually obtained by the action of iodin on alcohol, in the presence of an alkali or an al- 1. An agreeable, and at the same time efficient, mouth wash is obtained by mixing equal parts of aqua hydrogeni: dioxidi, liquor antisepticus (U. S.) and a saturated solution of potassium chlorate. 36 PHARMACOPEIA AND PHYSICIAN. kaline carbonate. Iodoform was discovered by Serullas, in 1822, but was not used in medicine until some time after 1837. Despite its disagree- able penetrating odor, iodoform continues to bold first place among local antiseptics, used for tbe dressing of wounds. At first it was supposed to share with chloform (from which it differs chem- ically only in the iodin displacing the chlorin) a strong antiseptic action, but in the case of iodo- form, this has been found to be but slight; it is, however, materially increased by the slow libera- tion of iodin. When its local use as a dressing is long continued, enough of it may be absorbed to produce poisoning, which does not, however, re- sult in typical narcosis, such as chloroform pro- duces, but gives rise to disturbances of cerebration, headache, delirium and other symptoms. These are due to the iodoform molecule; but exanthem- ata, which are sometimes severe, are usually attri- buted to the liberated iodin, which, when liberated, is thought to circulate in the blood as an alka- line iodid or in combination with albumin. Hem- aturia, albuminuria and urinary casts may also re- sult from its absorption, and many attempts have been made to find a substitute for iodoform with- out its poisonous effects. Some surgeons deny that iodoform exerts any direct antiseptic power, and attribute the bene- fits from its use to its limitation of the secretion on which the bacteria would otherwise develop. Binz observed that iodoform lessened the emigra- tion of leucocytes, and it is said to be particularly useful in local affections with free secretions. When iodoform is intended for use as a dust- ing powder, its odor may be rendered ven r much LOCAL ANTISEPTICS. 37 less disagreeable by incorporating with it from 1 to 4 per cent, of cumarin. The following has been used to some extent: IJ. Iodoformi 3v 20 1 Cmnarini gr. xv 1| Acidi borici q. s. ad oxiii 50 1 Misce. bene. Sig. : To be used as a dusting powder. Pulvis Iodoformi Compositus (1ST. F.), contain- ing iodoform 20, boric acid 30, naphthalin 47, and oil of bergamot 3 parts, also constitutes a use- ful and comparatively unobjectionable antiseptic dusting powder. Where iodoform is to be used in the form of an ointment the addition of from 5 to 10 per cent, of balsam of Peru, or of 2 per cent, of oil of anise has been found to be advantageous. The addition of oil of anise, in somewhat larger quantities, has also been recommended for iodoform gauze, par- ticularly ' when the gauze is to be used in appre- ciable quantities or for any continued length of time. If the antiseptic action of iodoform is due to the liberated iodin, then necessarily many of the proposed substitutes must be practically de- void of antiseptic power, since the iodin is too firmly bound to be liberated by the tissues. Iodolum. — U. S. — Iodol designated chemically as tetra-iodopyrrol, one of the recent additions to the Pharmacopeia, illustrates this particular condi- tion very well. The iodin in this case is so thor- oughly combined that the substance has been rec- ommended as being comparatively non-toxic. An- other class of preparations, such as nosophen, loso- phan and europhen, depends for the antiseptic action largely on the cresol or the phenol com- pounds united to the iodin. Loretin and vioform 38 PHARMACOPEIA A ND PHYSICIAN. are combinations of iodin and quinolin, and there is no reason to suppose that they have any advan- tages over the other preparations just mentioned. Thymolis Iodidum. — U. S— Thymol Iodid much better known by the formerly trade-marked name “Aristol,” is a condensation product of two molecules of thymol with two atoms of iodin, and more properly, therefore, should be designated by its true chemical title, dithymol di-iodid. This preparation, which really belongs to the phenol group of iodin compounds, has met with a better reception than many of the other iodoform sub- stitutes. It is probable, now that the patents have expired on aristol and the substance is available at much more reasonable prices, that its popular- ity and use will be extended still further. This, however, is problematic. Schmiedeberg specifi- ally states that aristol, losophan, sozoiodol. picrol, loretin and antiseptol, all of which contain iodin, are not more actively antiseptic than are the cor- responding iodin free compounds, while the latter are, of course, much less expensive. Since the number of possible combinations of this tjqrn is practically unlimited, we will do well to exercise circumspection in accepting those which appear from time to time. Phenol. — U. S. — Acidum Carbolicum (U. S. P., 1890) is hydroxy benzene, and may be obtained from coal tar by fractional distillation and subse- sequent purification, or may be made synthetically. In its pure state it occurs as colorless, needle- shaped crystals, or as a white crystalline mass. Phenol Liqijefactum. — U. S. — Liquefied Phenol, Liquid Carbolic Acid, contains from 85 to 89 per cent, of absolute phenol, and is the form LOCAL ANTISEPTICS. 39 in which this substance is usually seen and used. Phenol or carbolic acid is now used as an anti- septic dressing for wounds very much less fre- quently than it was some years ago, because of the danger of poison due to absorption. It may be applied in the form of a 2 per cent, solution in water ; stronger solutions are used, but many cases of gangrene have followed the use of even dilute solutions on the extremities, particularly the hands, for a continued length of time. A sharp distinction is to be drawn between the anesthetic and antiseptic uses of phenol. Solu- tions of phenol in oil, or mixtures with fats, are excellent anesthetics when brought in contact witli painful surfaces or wounds, hut they possess very little antiseptic action, because phenol is more sol- uble in fats and oils than in -water or weak saline solutions, hence it does not leave the oil to pene- trate the bodies of bacteria, without doing which it does not injure them. Practically the same holds true of its affinity for alcohol, and it is for this reason that alcohol is such an excellent antidote for carbolic acid, exter- nally as well as internally. The absorption of phenol is followed by its appearance in the urine, which usually becomes dark greenish or nearlv black in color. Cresol. — IT. S. — and its more desirable form : Liquor Cresolis Comi>ositus. — II. S. — Com- pound Solution of Cresol has been mentioned under general disinfectants. The latter compound has been extensively used, particularly in the form of one or the other of the numerous proprietary preparations, as a local disinfectant and also as an antiseptic. The saponaceous properties of this 40 PHARMACOPEIA AND PHYSICIAN. particular preparation make it very useful in a variety of instances in -which a detergent action is to be attained in addition to the disinfection. Thymol. — U. S. — This is a phenol occurring in the volatile oil of Thymus vulgaris and in some other volatile oils. It possesses strong antiseptic properties, but its comparative insolubility in water, 1 in 1,100, has interfered materially with its extended use. Thymol iodid, the only official combination of thymol, has been referred to in con- nection with iodoform substitutes. An ideal disinfectant, or antiseptic dressing for wounds, should act strongly on the living proto- plasm, should be slowly absorbed, and should af- fect the central nervous system but slightly after absorption. Phenol has the disadvantage of being rapidly absorbed and of profoundly affecting the central nervous system. Thymol, being but slight- ly soluble in water, but volatile at ordinary tem- peratures, is slowly absorbed, and, as its excretion keeps pace with its absorption, there is little dan- ger that it will exert a poisonous action when used locally. Resorcinol. — U. S. — Resorcinum (U. S. P. 1890), a diatomic phenol that is usually referred to by its popular name, resorcin, was at one time extensively used in dermatologic practice, but is now seldom employed except for scalp diseases and sometimes internally. Pyrooallol. — U. S. — This is better known as pyrogallic acid and is a triatomic phenol, some- times used in dermatologic practice. Actdum Salicylicum.— U. S. — Salicylic Acid has been used to some extent as a local antiseptic, particularly in the form of dusting powders, di- LOCAL ANTISEPTICS. 41 luted with talcum, zinc oxid or boric acid. Sali- cylic acid is used extensively in dermatologic prac- tice, particularly in the form of ointment. It is only slightly soluble (1/310) in'water. The practice of dermatology involves a special knowledge of antisepsis, and the subject can be given only general consideration at this time, so that we must content ourselves with little more than a simple enumeration of some of the official substances that are used, merely suggesting the number and variety of the available materials. Pix Ltquida. — IT. S.— Tar, a product obtained by the destructive distillation of the wood of one of several species of Finns, has been widely used in the treatment of skin diseases, usually in the form of an ointment. Unguentum Prcis Liquids. — U. S. — Tar Ointment contains 50 per cent, of tar. Oleum Cadinum. — U. S. — Oil of Cade, or oil of juniper tar, is a product of the dry distillation of Juniperus Oxycedrus and is closely allied to tar, being used in the same way. Balsamum - Peuuvianum. — IT. S.- — Balsam of Peru will be referred to again under expectorants. Its antiseptic properties are probably due to the benzoic and cinnamic acids which it contains. It is used in dermatology, either in ointment or in collodion. Na phthalenum . — U. S. — Naphthalene or naphtalin and B etaxapptthol. — IT. S. — Naphtol, are used in dermatologic practice, though the former, at least, has practically fallen into disuse for medicinal purposes. 42 PHARMACOPEIA AND PHYSICIAN. Among other substances having antiseptic prop- erties, used locally, we have: Sulphur Precipitatum. — U. S. — Precipitated Sulphur. This and the other official forms of sul- phur will be mentioned in connection with cathar- tics. Sulphur constitutes a most important agent in the treatment of a number of skin diseases. It is applied either in the form of lotions or of oint- ments. For the former, precipitated sulphur is usually preferred, while in ointments either Sulphur Sublimatum. — U. S. — Sublimed Sulphur, or Sulphur Lotum. — U. S. — Washed Sulphur is used. In the official Unguentum Sulphuris. — U. S. — Sulphur Ointment, 15 per cent, of washed sulphur is di- rected to be used. This ointment is now only half the strength of that formerly official and is, there- fore. better suited as a mildly stimulating anti- septic application. Sodii Ttiiosulphas. — U. S. — Sodium Thiosul- phate, better known as sodium hyposulphite, is another useful antiseptic that is now little used medicinally, except in dermatology. It is freely soluble in water and is usually prescribed in the form of a lotion. It is said to be particularly use- ful in the destruction of parasitic fungi which in- fest the skin. Glycertkum. — U. S. — Gtycerin is not alone useful as a mild antiseptic, but is also extensively used as a vehicle for many other substances in the treatment of skin lesions. Glyceritum Amyli. — U. S. — Glycerite of starch is a preparation that was introduced many LOCAL ANTISEPTICS. 43 years ago to serve as an ointment base in cases in which lard or fat might prove objectionable. MERCURIALS. Hydrargyri Iodidum Rubrum. — U. S. — Red Mercuric Todid or biniodid of mercury is the most active of all the official germicides and antiseptics. It is comparatively expensive, however, and is only slightly soluble in water. Hydrargri Chloridum Corrosivum. — U. S. — Corrosive Mercuric Chlorid, bichlorid of mercury, mercuric chlorid, or, more properly, corrosive sublimate, is by far the most popular and most generally used of all local chemical disinfectants and antiseptics. It is extremely poisonous and many fatalities have occurred from its use, even in the vagina and in the washing of wounds. Gauze impregnated with a solution of mercuric chlorid is often placed over small or closed wounds to prevent the access of bacteria. It is widely used as an antiseptic and disinfectant, but it is extremely caustic and can not be applied to mu- cous membranes and to open wounds except in very dilute solutions, for fear of absorption. Mercuric chlorid is slowly but completely solu- ble in 13 parts of water and in 3 parts of alcohol. The solubility of this substance in water is much facilitated by the presence of other soluble chlorids. This fact has been utilized in the preparation of the commercial tablets of mercuric chlorid that are sold for making antiseptic solutions. These tablets usually contain about 0.5 gm. (7.5 grains) each of mercuric chloric! and ammonium chlorid, the sal alembroth of the alchemists, which, when dissolved in 500 c.c. (1 pint) of water make a solu- 44 PHARMACOPEIA AND PHYSICIAN. tion of 1 to 1,000. This solution is useful for the disinfection of the hands, for walls and floors and for man}'' fabrics that are not injured by water. Mercuric chlorid attacks metals and, therefore, must be avoided with metal instruments. It is a very popular insecticide and a number of the mercurials are used as parasiticides, notably for pediculi. For this purpose, however, the various ointments of mercury are preferable. Unguentum Hydrargyri. — TJ. S. — Mercurial Ointment, contains 50 per cent, of mercury. Unguentum Hydrargyri Dilutum. — U. S. — Blue Ointment, a new addition to the Pharmaco- peia, contains 33 per cent, of mercury and con- forms more closely to the proposed international standard for mercurial ointment. Another oint- ment that is sometimes used as a parasiticide is Unguentum Hydrargyri Oyidi Rubri. — U. S. — Ointment of Red Mercuric Oxid, or red precipi- tate ointment, containing 10 per cent, of red mer- curic oxid. ANTISEPSIS OF THE MUCOUS MEMBRANES. The antisepsis of the mouth is important, not only because of the infectious diseases pertaining to it, but also because of the excellent opportunity that is afforded to micro-organisms to multiply there in enormous numbers on the particles of food in the cavities of teeth or wedged between them. That this is true is shown by the putrid smell acquired by particles of meat which remain but an hour or so in the mouth. The extent to which bacteria may increase may be inferred from tbe calculation, given by ISTovv, that 30,000,000.- LOCAL ANTISEPTICS. 45 000 contain less than one-sixth of a milligram (1/400 grain) of organic matter. The main factor in securing antisepsis of the mouth is cleanliness. If the teeth are carefully cleansed and all organic matter removed, the bac- teria have less on which to thrive, and mild anti- septics then fully suffice to keep the number with- in bounds. Liquor Antisepticus.— " IT. S. — Antiseptic So- lution is a new addition to the Pharmacopeia, con- taining 2 per cent, of boric acid with aromatic an- tiseptic volatile oils. It is designed to be used as a mild antiseptic lotion or wash. 2 The official antiseptic solution is also useful as a gargle, preferably diluted with an equal quantity of water. The use of hydrogen dioxid as a spray or gargle, as well as its use in connection with the official antiseptic solution, has been mentioned. Potassii Chloras. — IT. S. — Potassium Chlor- ate, while not a particularly active antiseptic, has 2. The official antiseptic solution is slightly acid. When an alkaline antiseptic mouth wash is desired it will be well to use the “Alkaline Antiseptic Solution’’ of the National Formulary. Either one of these preparations can readily be prepared by any trained pharmacist. They are very inexpensive and should be given the' preference over the various nostrums that are not alone exploited as local anti- septics, but are also advertised as sure cure remedies for a very large number of intestinal disorders. The working formula for the alkaline antiseptic solution is as follows : Fotassium bicarbonate Sodium benzoate, fin 3 i 32 Borax oil 8 Thvmol . . . grs. iii Eucal.vptol, Oil of peppermint, aa m. iii Oil of wintergreen m vi Tincture of cudbear 3iv 15 Alcohol SH 60 Glycerin Jvui 250 Water, sufficient to make. . . . . . .Sxxxiv 1000 46 PHARMACOPEIA AND PHYSICIAN. long been favorably known to be a desirable addi- tion to gargles and mouth washes. It is soluble in 16 parts of cold water and is generally used in saturated solution, from which traces of chloric acid may possibly be liberated. Alum and boric acid are also useful as gargles. After the use of any of these gargles the mouth should be well rinsed with water to prevent injury to the teeth. The antisepsis of the nasal passages is usually accomplished by thorough cleansing w T ith warm sa- line solution (0.9 per cent.), nine grams (135 grains) to a liter (quart) of water, or by a mild alkaline solution made by adding nine grams (135 grains) of sodium bicarbonate to the saline solu- tion just mentioned, after which a mildly antisep- tic solution, such as the official, is used as a spray or douche, or, in lieu of this, one-tenth of 1 per cent, of phenol may be added to the saline douche, but the latter is not recommended as a routine practice. 3 It may be permissible here to enumerate some of the substances that have been or are used as mild antiseptic applications to the mucous mem- branes. Acidum Bokicuh. — U. S. — Boric Acid, gen- erally referred to as boracie acid, is quite free 3. The pharmacopeia of the German Hospital, Philadel- phia, contains a formula for an alkaline antiseptic tablet that has found favor with some. It contains 0.25 gm. (about 4 grains) each of sodium bicarbonate, sodium borate, sodium chlorid and sodium phenosulphate, with 0.005 gm. (about 0.1 minim) of oil of cinnamon. One of these tablets (the same' mixture can also be directed in powder) is to be dissolved in six tablespoonfuls of recently boiled water and used as a wash for the nose. LOCAL ANTISEPTICS. 47 from toxicity. It is soluble in about 16 parts of water and is but slowly absorbed. Glyceritum Boroglycerini.— U. S. — Glvcer- ite of Boroglycerin, contains 30 per cent, of boric acid and has the same uses as that acid. Sodii Boras. — U. S. — Sodium Borate, or borax, has an alkaline reaction and is sometimes preferred to boric acid on this account. It is soluble in six- teeen parts of water. Somi Chi.oridum. — U. S. — Sodium Clilorid, common table salt, has been in use as an antiseptic from time immemorial, and the only reason we have for presenting it here is to call attention to the fact that the Pharmacopeia recognizes it as a valuable article of the materia medica and pro- vides certain standards and tests for purity. Sodii Piienolsulphonas. — U. S. — Sodium Phenol sulphonate, the sodium sulphocarbolate of former editions of the Pharmacopeia, is another mild antiseptic that has limited but well-defined uses. Practically all the salts of the alkalies have anti- septic properties, but it is obviously not necessary to recount all of them at this time. Complete disinfection of the nose, mouth, throat, vagina and urethra is not practicable, and is not even necessary ; the main thing to be sought is the cleansing of those regions from pus and organic matter on which bacteria thrive. Mucous mem- branes decompose the solution of hydrogen dioxid with such copious evolution of oxygen that it can not be used in the nose, and because of this rapid action by the mucous membrane itself, a large amount frequently repeated is necessary to com- pletely disinfect such cavities. 4 48 PHARMACOPEIA AND PHYSICIAN. The antisepsis of the eye is confined largely to the use of camphor water, boric acid and sodium borate. In virulent affections more active antisep- tics are sometimes indicated; in these cases weak solutions of mercuric chlorid, copper sulphate, zinc cblorid, silver nitrate or formaldehyd are used. These substances, however, are all extremely irri- tating and great caution is required. Their use by the general practitioner is not advised . 4 5 Some years ago J. Stilling recommended the use of the anilin colors, more especially pyoktannin blue and pyoktannin yellow, as weakly antiseptic applications to the eye. Pyoktannin yellow is still used to some extent either as powder, pencil or in watery solution. Burns or scalds resulting in destruction of the skin should be treated antiseptically. Treves di- rects that the burn be washed with a solution of 4. For use in the vagina, where a simple detergent and antiseptic action is sought, the official Liquor Cresolis Com- positus in 0.5 to 1 per cent, solution will be found to be all that is required. When an astringent effect is desired the following formula for an antiseptic astringent powder will be found to answer the purpose very well : R. Sodi boratis Sil 60 Alumen exsicc 3x 40 Thymol, Phenol, A llCU Ul, Eucalyptol Olei gautheri®, aa gr. vlil 5 M. Sig. : A heaping teaspoonful to be dissolved in one liter (1 quart) of hot water, to be used as a douche. 5. The method of using boric acid in the eye varies greatly, but usually a 2 per cent, solution of boric acid in equal parts of distilled water and camphor water will be found to be sufficient. When it is desired to use sodium borate in connection with boric acid the following will be found satisfactory : JJ. Acldi boric! gr. xv 1. Sodii boratis gr. xxx 2 Aqu® dest., Aqu® camphor®, aa XIss 50 LOCAL ANTISEPTICS. 49 hydrogen dioxid and then with a solution of boric acid ; the vesicles are then opened with an aseptic needle and the surface dusted with iodoform and dressed with aseptic cotton. Linimentum Calcis. — U. S. — Lime Liniment, or Carron oil, so called from the name of the iron works in England where this preparation had its origin, consists of equal parts of lime water and linseed oil. It has long been in use as a popular dressing for superficial burns and constitutes a readily applied and effective non-antiseptic remedy that rapidly allays the accompanying pain. If there has been extensive destruction of tissue, this remedy should be avoided, as it is not alone diffi- cult to remove, but also forms a covering beneath which bacteria may proliferate safe from the reach of antiseptics. Potassii Permaistganas. — U. S. — Potassium Permanganate, already referred to under the head of general disinfectants, is often considered to be devoid of antiseptic properties because of the readi- ness with which it oxidizes all organic matter. It is true that potassium permanganate is readily de- composed by the organic matter with which it first comes in contact, and that it would be unusual in- deed to find bacteria the only form of organic mat- ter present in any one case. When we remember, however, that a very large number of bacteria represent but an infinitesimally small amount of organic matter, we will appreciate why potassium permanganate is capable of destroying vast num- bers of micro-organisms in those cases in which its action can be confined to them. This substance finds its greatest usefulness as a local application in rendering foul ulcers odorless. 50 PHARMACOPEIA AND PHYSICIAN. For this purpose a fairly strong solution, 2 per cent., is freely used as a wash. Much weaker solu- tions are sometimes used with great benefit as urethral irrigations in gonorrhea and as vaginal douches. A hot 1 per cent, solution of potassium permanganate will be found extremely useful as a deodorizer for instruments after use in the vagina while awaiting sterilization. Potassium perman- ganate destroys some alkaloids much more quickly than others, e. g., morphin more readily than strychnin. It can not enter the circulation, hence, when swallowed, it can act only on the substances found in the stomach. Obviously it is not suited for hypodermic injections. CHAPTER III. INTERNAL ANTISEPTICS. The great strides made in the use of antisep- tics, after Lister had employed them in surgery with such brilliant results, led to the hope that they might be made available for limiting the de- velopment of bacteria in various parts of the hu- man bodj r . Erom time to time clinicians have re- ported favorable results from the use of internal antiseptics in such diseases as typhoid fever, but at the present time it is generally acknowledged that complete disinfection of the intestinal tract is impossible and that the treatment of constitutional diseases by means of antiseptics is possible only in a few isolated cases; for example, in malarial fever by quinin, in articular rheumatism by sali- cylic acid and its compounds, and in syphilis bv means of mercurials. Quinin has been shown to have a peculiarly selective and destructive action on the protozoon which causes malarial fever, and perhaps mercury and salicylic acid may possess similar selective action against the agents produc- ing syphilis and certain forms of rheumatism. It is no longer considered probable that there will be found any agent or group of agents capable of rendering the blood and tissues sterile to all or to any considerable number of bacteria; but it is ad- mitted that we may yet find many agents, each ex- erting an influence analogous to that of quinin in malarial fever; we may limit ourselves, therefore, to the discussion of the probable action of antisep- 52 PHARMACOPEIA AND PHYSICIAN. tics on the alimentary canal and of the three sub- stances just enumerated. It is impossible to form a correct idea of the probable effect of an internal antiseptic without having at least some idea of the organisms on which it must act. Nuttall and Thierf elder took guinea-pigs from their mother by Cesarean section under aseptic conditions, and fed one of them on sterilized food for thirteen days, during which it continued to strive, but Schotelius found that chickens died of starvation when fed only on sterilized food. G. 1ST. Stewart accepts Nuttall and Thierf elder’s re- sults as demonstrating that animals, including man, exist, despite the bacteria which infest the alimentary canal from a few hours after birth until death. Strassburger concludes, from a review of the extensive literature pertaining to intestinal bac- teria, that Nuttall and Thierfelder have shown that no single process of alimentation is absolutely de- pendent on bacteria, but that the chief function of certain of them, notably the colon bacillus, which is always abundantly present, is actually to destroy other bacteria and thus to protect the host against those disease germs which may gain entrance to the alimentary canal. The destruction of all the bacteria in the alimentary canal at any one time, therefore, might prove fatal, in that any disease germs which chanced to gain access to the intestine could so multiply as quickly to destroy the life of the host. The proof that bacteria do play some part in the process of digestion is found in the fact that man can digest the cellulose of delicate vegetables to a INTERNAL ANTISEPTICS. 53 limited extent, though he secretes no enzyme cap- able of splitting cellulose, which, therefore, must be split by bacteria present which have been shown to possess that power. Then, too, certain crystal- line bodies other than leucin and tyrosin have re- cently been found among the ultimate products of digestion, and as none of the known digestive enzymes are capable of forming these bodies they likewise must result from bacterial action. While we must admit that bacteria are concerned in digestion, we have no positive information at the present time as to how important a part they ac- tually take. It has been shown that the colon ba- cillus, which is universally present in milk, inhib- its, to a certain extent, the action of putrefactive bacteria, and it is well known that untreated milk of good quality is more digestible than is the same milk after sterilization . 1 We are thus forced, by this and other like evi- dence, to conclude that it is by no means desirable to render the intestines sterile and that, instead of 1. Tests made on the several constituents of milk show that they have no power to inhibit putrefaction, though, such a power is unquestionably possessed by fresh milk. That this is due, at least in part, to certain bacteria nor- mally present in the milk is shown by the fact that sterilized' milk putrefies much more rapidly than untreated milk on the addition of the bacillus of putrefaction ( B . putriflcus) ; but if with the Bacillus putriflcus the colon bacillus be added to sterilized milk, the milk acts as does normal milk, thus proving that the colon bacillus is actually capable of inhibiting the development of certain bacteria. It is, of course, possible that fresh milk also possesses antibacterial properties which are destroyed by the sterilization. These conditions help to explain why sterilized milk is not so wholesome as new milk of good quality. It must be remem- bered, however, that milk is an excellent culture medium in which a great many bacteria are normally present, and that if it be allowed to stand in a warm place for some hours 54 PHARMACOPEIA AND PHYfHCIAX. attempting intestinal antisepsis in the broader sense, we should seek rather to modify the flora in that region than to destroy it. Various .methods have been proposed, from time to time, for determining the relative degree of putrefaction taking place in the intestines, but at the present time it is not positively known what constitutes the best method at bur disposal for doing this. The procedure most frequently em- ployed, one which is considered to afford a fair es- timate in a large proportion of cases, consists in es- timating the ethereal sulphates in the urine. Strass- iburger claims that weighing the bacteria after sep- aration from the feces and drying affords the surest means of estimating the number of bacteria pres- ent. Others count the number of colonies which can be cultivated from a milligram of feces, but this has been shown to be unreliable. In view of the fact that laboratory methods are far from satis- factory in determining the number of the several varieties of bacteria present in the feces, the gen- eral practitioner will probably be obliged, for some the micro-organisms multiply to such an extent that the milk is wholly unfit for use, and we do not wish to be mis- understood as implying that the colon bacillus is afi un- mixed blessing. While, during health, the micro-organism probably does not emigrate from the uninjured intestine it may do so in states of lowered general resistance, or in the presence of defects of the intestinal epithelium, and may give rise to blood infection, or more rarely to inflammations in various organs. The possibility that the bacillus of typhoid fever and kindred forms are only modified colon bacilli is of theoretical importance. Some authorities (Escherich and some others) deny that the colon bacillus is capable of rap- idly becoming virulent. Different strains of the colon bacil- lus have different degrees of virulence, and it still remains possible that many cases of infantile' colitis are caused by certain strains (e. g., the colicolitis of Escherich). 1 N Tli Ills A L A N TISEPTICS. 55 time to come, to depend largely, if not entirely, on the clinical data presented by each individual case. Without knowing the precise role played by the multitudinous bacteria of many species, we do know in various ways when undue activity of .the putrefactive bacteria occurs and certain symptoms give notice that excessive fermentation is taking place in the small intestine. A moderate increase in the number of colon bacilli tends to lessen the development of the putrefactive germs; on the other hand, an intestinal catarrh, caused by exces- sive acidity resulting from the undue fermenta- tion of carbohydrates by the colon bacillus, may be alleviated by lessening the carbohydrates of the food and consequently the medium on which the colon bacillus thrives. Normal peristalsis, by hurrying the food through the small intestine, prevents undue development of bacteria, but diarrhea and irritant purgatives favor the development of bacteria by the increased amount of liquid which is present, because of the increased secretion of diminished absorption. Thus more bacteria have been found after administra- tion of calomel than were present before the drug had been given, though calomel is generally con- sidered to be an excellent antiseptic. While normal peristalsis limits the develop- ment of bacteria, the latter, in turn, liberate acids in the decomposition of carbohydrates which prob- ably supply the stimulus which sets up peristalsis. The normal digestion and absorption of food also tend to lessen intestinal putrefaction by lessening the amount of material which can serve as a cul- ture medium. It is important that the intestinal wall should 56 PHARMACOPEIA AND PHYSICIAN. be kept intact. When the intestinal mucosa is in- jured it fails to absorb the food products and the bacteria multiply rapidly. It has been found that many antiseptics injure the intestinal wall more than they do the bacteria, and, despite the fact that the antiseptic may be found in quantity in the feces when the bulk is small, it has actually permit- ted an increased growth of micro-organisms in the small intestine when other conditions favored the bacteria and not the antiseptic action. Strass- burger found just double the number of bacteria after the use of naphthalene, which has been con- siderably lauded as an intestinal antiseptic. As suggested before, the simplest means of di- minishing the number of putrefactive bacteria is by lessening the amount of the proteid of the food. Though it has been contradicted by the indirect evidence of urinary constituents, it has been shown that the bacteria of the intestines are very much reduced in number by the withdrawal of all food. It was formerly supposed that the gastric juice of the stomach interposed a fairly effective barrier to the entrance of living disease germs into the in- testine. but this juice has but little effect at the be- ginning of digestion, when the activity is slight, and toward the end, when the hydrochloric acid is nearly all combined with proteid. Some micro- organisms, e. g., the tubercle bacillus, pass unin- jured through the stomach more readily than oth- ers, e. g., the vibrio of cholera. The effect of bile on bacteria is not positively known, but it is generally supposed that it does not contain any germicidal power, as some bacteria'can be cultivated on bile, though not after the precipi- tation and removal of the mucus. The intestinal INTERNAL ANTISEPTICS. 57 secretion does not possess any germicidal power. All these factors are important, since all of them — bile, gastric juice and intestinal secretion — have at various times been supposed to possess antiseptic properties, and it is necessary to know what results are to be expected from increasing the quantity of any or all of them. Strictly speaking, the antisepsis of the alimen- tary canal should begin with that of the mouth, but this is more conveniently considered under local antisepsis. In view of the fact that the gastric juice does not interpose an absolute barrier to the ingress of pathogenic bacteria to the intestine, the proper care of the mouth and the limitation of its flora assumes an added importance, and there is no question of the fact that proper attention to the cleanliness of the oral cavity will greatly lessen the danger from intestinal infection. The general tone of these varied statements may appear pessimistic, so far as faith in the efficiency of intestinal antisepsis is concerned, but so far from that being the case they are intended to fur- ther demonstrate that our main reliance must, after all, be placed in guarding against the entry of disease-producing organisms into the alimentary canal and their destruction before they have passed beyond the reach of local treatment. After they have once gained admittance to the intestine the best means of limiting their development must be sought in regulating the diet and careful attention to the general condition. If we are unable to destroy all or even any appreciable number of the bacteria of the intestine, it is consoling to know that some of them are our allies instead of our foes. It is admitted by nearly 58 PHARMACOPEIA AND PHYSICIAN. all authorities that it is impossible to influence the bacillus of typhoid fever by antiseptics. It has been shown that a milk diet hinders the develop- ment of putrefactive bacteria, and many consider that the main benefit derived from a milk diet in typhoid fever is due to its effect on bacterial devel- opment. Fortunately, the Bacillus typhosus does not form spores and the bacillus itself is easily killed outside of the bod} r ; heating in water even to 75 C. (1G7 F.) for ten minutes greatly lessens its vitality. It is practically impossible in the space at our disposal even to summarize the results of the hun- dreds of investigations dealing with the question of intestinal antisepsis. Those experiments which ap- pear more nearly free from error point to the fact that we can not secure direct antiseptic action by chemical antiseptics in the intestine without injur- ing the intestinal wall, or at least materially reduc- ing those conditions which naturally limit bacter- ial development, more than we injure the bacteria. The net result, therefore, is usually an actual in- crease of some species and a dimunition of others. Clinical experience seems to prove conclusively that the mild mercurous chlorid, or calomel, is bene- ficial in those cases of indigestion which are char- acterized by that train of symptoms which includes a feeling of dullness, lassitude, headache, nausea and anorexia, the condition being popirlarlv termed “biliousness:” It is possible that the antiseptic ac- tion of the calomel, by limiting the development of other species of bacteria, gives the colon bacillus a chance to multiply, the increased amount of fluid in the intestine having been found particularly to favor its development. These, in turn, may then INTERNAL ANTISEPTICS. 59 modify digestion or serve to restrict the develop- ment of putrefactive bacteria, and, as we have seen, they favorably influence peristalsis, which in turn is one of the natural means of elimination of bac- teria. The increased peristalsis caused by the cal- omel lessens the opportunity for absorption of the bacterial toxins which give rise to the train of symptoms mentioned ; this lessened absorption may be due in part to the action of calomel on the wall of the intestine. This merely suggests the many- sidedness of an operation that appears at first glance to be a very simple one. The action of the solution of hydrogen dioxid in the mouth and throat has been discussed under local antiseptics. Owing to the rapidity with which it is decomposed by mucous membranes it can exert but little germ- icidal action in the stomach and absolutely none in the intestine or general circulation ; indeed^ it is so rapidly decomposed by the blood that it speedily causes death by embolism when introdced into the circulation. The same holds true of potassium per- manganate. and it is probable that all antiseptics that depend for their action on the liberation of oxygen would be decomposed in the same way when brought in contact with the mucous membranes of the mouth and throat or the organic material neces- sarily present in the stomach. Acidum Hydrociilortcum.— U. S. — Hydro- chloric Acid, or muriatic acid, contains 31.9 per cent, of absolute hydrochloric acid. It is seldom used in medicine in this country, the preference being usually given to Acidum Hydrocttloricum Dilutum. — IT. S. — Diluted Hydrochloric Acid, containing 10 per cent, of absolute hydrochloric acid. This acid undoubt- 60 PHARMACOPEIA AND PHYSICIAN. edly exerts some germicidal action in the stomach when present in sufficient amount, and its action may directly influence the intestinal flora. It has been stated that the hydrochloric acid of the stom- ach becomes bound to albumin during digestion and then exerts no antiseptic influence, but we have also seen that normal digestion is one of the surest means of controlling the bacteria of the in- testine, and how a deficiency of that acid may cause fermentative dyspepsia, with an enormous increase of bacteria, which may become virulent. It may be mentioned in this connection that, according to some recent experiments on man, the usual dose of dilute hydrochloric acid, 1 c.c. (15 minims) is -entirely too small to supply the deficiency existing in many cases, and as much as 200 c.c. (6 fluid ounces) of 0.4 per cent, acid, corresponding to 10 c.c. of the official dilute acid, has been given with decided benefit when the usual dose or less had given no appreciable result. It must always be given diluted with a large amount of water. It should be remembered that mineral acids are to be taken through a tube to avoid injury to the teeth, and that the mouth should then be rinsed with water, or, better still, with a mild alkaline solu- tion, 2 such as limewater or a very dilute solution of sodium bicarbonate. Naphthalenum. — U. S. — Naphthalene, naph- talin and 2. The following has been used to a considerable extent In the treatment of gastric fermentative dyspepsia, partic- ularly when accompanied by nervous disturbances : R. Sodii bromidl gr. v 13 Resorcinoiis <. . . gr. ii j 1 Aquse anisi q. s. ad 3ii 10 1 This dose to be' taken after meals in half a glass of water. INTERNAL ANTISEPTICS. 61 Betanaphthol. — IT. S. — Betanaphthol, or naphtol, have been highly recommended as intes- tinal antiseptics. As we have seen, they do not usually lessen the number of bacteria, though they may exert a favorable, modifying action. These substances have been used in the treatment of diar- rhea with excessive putrefaction. The average dose of naphthalene is given as 0.12 gm. (2 grains), and the average dose of beta- naphthol as 0.25 gm. (4 grains). It has been sug- gested that naphthalene must be converted into betanaphthol before it can exert its antiseptic ac- tion, but even this point has not been satisfactorily determined. There are a number of nostrums on the market consisting of betanaphthol combined with astring- ents, but in view of the complex nature of the prob- lem with which we have here to deal it is preferable by far to employ the official substances, combining them as seems indicated in each case. To do this it is merely necessary to calculate the relative amount of each powder to be given at a dose and to dispense them either separately or in a single powder or a mixture. Betanaphthol and bismuth subnitrate or subcar- bonate may be combined somewhat as follows : R. Bismuthi subnitratis 3i 4| Betanaphthol gr. xv 1[ M. Sig. : To be made into ten powders, one being given every two hours in diarrhea and with foul-smelling feees. R. Bismuthi subnitratis 3iiss 10 [ Betanaphthol 3ss 2| Syrupi acaciae Biss 50 1 Aquae camphorae to make Biii 1 00 1 One teaspoonful to be given, after shaking, every two hours. 02 PHARMACOPEIA AM) PHYSICIAN. The number, as well as the variety of substances that have been suggested from time to time as in- testinal antiseptics may perhaps justify a more ex- tended review ; we can do little more, however, than simply enumerate some of the official substances that have beep, used and are even now being lauded as valuable and efficient remedies in the treatment of the several gastrointestinal disorders. The use of antiseptics in the treatment of ty- phoid and typhus fevers was first suggested in Ger- many more than thirty years ago. and the argu- ments that were offered at that time appeared so plausible that internal antiseptics at once sprang into vogue. Among the more popular were the fol- lowing : Iodum. — IT. S. — Iodin is very seldom used as such at the present time, although it is official. Average dose: 0.005 gm. (5 mg., 1/10 grain). Liquor Iodt Compositus. — U. S. — Compound Solution of Iodin, better known as Lugol’s solution, contains about 5 per cent, of iodin and 10 per cent, of potassium iodid in distilled water. This was at one time a favorite method of administering iodin. Average dose: 2 c.c. (3 minims). Tinctura Iodi. — U. S. — Tincture of Iodin is virtually a new preparation and combines the strength of the former official tincture with the water-soluble properties of the unofficial compound tinctures, or soluble iodin solutions. It contains 7 per cent, of iodin and 5 per cent, of potassium iodid in alcohol. Average dose: 0.1 c.c. (IV 2 minims). Iodin and the water-soluble preparations of iodin were formerly much lauded as intestinal antisep- tics, and even at the present time, though, as was INTERNAL ANTISEPTICS. G3 shown in the introductory portion of this article, the practice is now obsolete, they are frequently ex- ploited by manufacturers of nostrums as being lit- tle short of the ideal. The form in which iodin was formerly largely used was in connection with carbolic acid or phenol, thus : R. Tinct. iodi 3iiss 10 1 Phenol m. lxxv 5\ M. Sig. : y 2 to iy 2 minim three times a day in water. Phenol itself is now seldom employed, or even recommended, as an intestinal antiseptic, but the official phenol sulphonates, better known as sulpho- earbolates, still have a number of ardent advocates. Sodii Piien'olsulphonas. — U. S. — Sodium Phenolsulphonate, the sodium sulphocarbolate of the previous Pharmacopeia. Average dose: 0.25 gm. (4 grains). Zixci Phenolsulphonas. — U. S. — Zinc Phe- nolsulphonate, is rather more active than the sodium salt, combining the astringent properties of the zinc with the antiseptic properties of the phenolsulphonie acid. Average dose: 0.12 gm. (2 grains): Both the official salts are readily soluble in water and may be given in solution. Calcium phenol- sulphonate is being lauded at the present time as an intestinal antiseptic, but there is no reason to be- lieve that it offers any advantages over the sodium salt, and it is probably quite as harmless. Of the official derivatives or substances coming directly under the same classification as phenol we have : Thymol. — U. S.— Average dose: 0.12 gm. (2 grains). 64 PHARMACOPEIA AND PHYSICIAN. Ceeosotum. — U. S. — Average dose: 0.2 c.c. (3 minims), Gtjaiacol. — U. S. — Average dose: 0.5 c.c. (8 minims),. Guaiacolis Carbonas. — U. S. — Average dose : 1 gm. (15 grains), Acidum Salicylicum. — IT. S.— Average dose: 0.50 gm. (Ingrains), Phenylis Salicylas. — IT. S. — Phenyl Salicy- late, better known by its former official title, salol, is even now considered as being among the few really desirable or available internal antiseptics. It occurs as a white crystalline powder, having a faint but characteristic odor and a slight, rather peculiar taste; it is only slightly soluble in water, and, therefore, does not dissolve to any appreciable extent in the juices of the stomach. It is decom- posed, however, by the alkaline liquids of the intes- tine into its constituents, phenol and salicylic acid, and thus becomes available as an antiseptic. It is said to be particularly useful in preventing the in- fection of the kidneys by the Bacillus typhosus. Average dose: 0.50 gm. (7% grains). Hexamethylenamina. — IT. S. — Hexamethvl- entetramin will be discussed at greater length un- der diuretics (Chapter Y). This substance has also been recommended as an available intestinal anti- septic, but, as noted under diuretics, the ultimate products of its decomposition are largely, if not en- tirely, eliminated by the kidneys, and it no doubt finds its greatest field of usefulness in preventing possible infection of the urinary organs. Average dose: 0.25 gm. (4 grains). Tt is manifestly impossible to discuss or even to mention all the agents that have been, or are, em- INTERNAL ANTISEPTICS. 65 ployed as intestinal antiseptics. Many of the reme- dies that are recommended as intestinal antisep- tics are also useful as anthelmintics. Notable among these is thymol, which has been referred to frequently of late as being a useful as well as an efficient anthelmintic. Though many efforts have been made to treat tuberculosis by means of internal antiseptics, the favorable influence which has so far been observed is to be attributed to the beneficial effects produced on the tissues, and not to any direct bactericidal action produced by the antiseptics themselves. Of the remedies that have been suggested for this pur- pose, creosote and guaiacol continue to be used, probably with some benefit. The whole problem, however, appears to concern curative effect and treatment rather than antisep- sis. Few articles in our materia medica possess any action so specific as that shown by cinchona or its chief alkaloid, quinin, in the treatment of certain forms of malarial fever. Cinchona bark itself owes its introduction into Europe to the fact that it was found to be efficient in the treatment of fev- ers of a malarial type. For many years after its introduction into Spain the Jesuits had the bark sent to them by their brethren in Peru and care- fully kept the source of its origin a secret, and the substance, therefore, became widely known as Jes- uits’ b^rk. Being virtually introduced as a nos- trum, or secret remedy, it need not surprise us when we find that it has frequently taken a most important part as one of the compotent parts of a variety of nostrums, even down to our own times. Quinin. the most valuable of the alkaloids of cin- 66 PHARMACOPEIA AX I) PHY SI Cl AX. chona, was discovered by Pelletier and Caventon in 1820, and is to-day one of the few substances in medicine that has met with a constantly increas- ing popularity. Quinin is official under no less than six different titles, in addition to the several scale salts and preparations that are not of direct interest in connection with its peculiar use in ma- larial fever, but which will be mentioned under the subject of bitters. Quinina. — U. S. — Quinin. Quinine Bisulphas. — U. S. — Quinin bisul- phate. Quininye Hydrobromidum. — U. S. — Quinin hydrobromid. Quinine Hydrochloridum. — U. S. — Quinin hydrochlorid. QuiNiNiE Salicylas. — U. S. — Quinin salicy- late. Quininte Sulphas. — IT. S. — Quinin sulphate. Average dose of any of these preparations : 0.25 gm. (4 grains). The physical properties of the several salts of quinin are so well known that they do not require a description at this time. The reasons for the popularity and use of some of these salts are not always apparent. In America the sulphate is used almost exclusively, while on the continent of Europe the hydrochlorid appears to be given the preference in nearly all cases. That each»of the several official preparations of quinin has some par- ticular point of merit is suggested by the follow- ing table, showing the relative percentage of anhy- drous alkaloid quinin in each and also the relative solubility in water and in alcohol: INTERNAL ANTISEPTICS. 07 Per cent, of Solubility Solubility anhydrous quinin. in water. in alcohol. Quinin 85.5 1750. 0.6 Quinin bisulphate. . . 59.5 8.5 18. Quinin h.vdrobromid . 76.6 40. 0.7 Quinin hydrochlorid. 81.5 IS. 0.6 Quinin salicylate . . 69.9 77. 11. Quinin sulphate . . . 74.3 720. 86. It will be noted that the very commonly nsed sulphate, next to the alkaloid itself, is the least soluble in the most common of all solvents, water : this, while a decided advantage so far as masking the taste of salt is concerned, is a marked disad- vantage in attempting to make a solution of the salt. Where quinin sulphate is to be given in so- lution it must be given in an acid mixture or in solutions that are so dilute that the quantity to be taken would be nauseating . 3 3. It is truly surprising that the sulphate of quinin con- tinues to be nsed almost to the exclusion of the alkaloid and the other salts. When a tasteless mixture is desired the alka- loid Is preferable because it is less soluble than any of the offi- cial salts ; if it is necessary to administer the drug in solution ten grains of the h.vdrochlorid may be given in a teaspoonful of a mixture containing 50 per cent, of alcohol, while three grains of the hydrochlorid, or seven of the bisulphate may be given in a teaspoonful of a watery mixture. The follow- ing is a type of the usual acid mixture : R. Quinin sulphatis grs. Ixxv 51 Acidi hydrochlorici dil m. ixxv 5] Elix. aromat. q. s Siii 100 1 When the salt, or better, the alkaloid, is to be given in a mixture, and the taste is to be masked, acids should never be added. Instead of the acid, a sweet substance, like gl.v- cyrrhizin, should be used to mask the bitter taste of the qui- nin. A satisfactory mixture is obtained as follows : R. Quininre vel quininm sulphatis. .grs. ixxv 51 Fid. ext. glycyrrhizae 3iv 15 Syrupi et elix. aromat. aa q. s 3ii 100 The more satisfactory method of administering quinin in the comparatively large quantities that are usually given is in cachets, gelatin capsules or pills. 68 PHARMACOPEIA AND PHYSICIAN. The use of quinin as a destroyer of the proto- zoon which causes malarial fever is among the best established facts of therapeutics. It is mentioned here largely to avoid the criticism of incomplete- ness rather than to offer any suggestions of nov- elty to the general practitioner. If fairly large doses of quinin be given four hours before the time at which the chill of malarial fever is expected to occur, and the dose repeated in two hours, the maximum effect of the quinin on the organism is obtained and the chill is usually prevented. The quinin existing in the blood at the time that sporulation occurs destroys the newly liberated organisms and the blood is rendered asep- tic so far as that particular organism is concerned. This process has to be repeated at intervals, some- times for three or four weeks. The use of salicylates in articular rheumatism is almost as well established as is that of quinin in malarial fever. The precise mode of action is not known, but it is surmised that its action is some- what analogous to that of quinin. We may be per- mitted to add a list of the official preparations that would properly come under this heading, just to show the extensiveness as well as the variety of the official preparations. Surely such a variety as we find here should enable us to choose the appropriate remedy of this type without the necessity of hav- ing recourse to any of the nostrums. Acidum Salicylictjm. — U. S. — Average dose: 0.5 gm. (7% grains). Sodii Salicylas. — U. S. — Average dose: 1 gm. (15 grains). Ammonii Salicylas. — IT. S. — Average dose: 0.25 gm. (4 grains). INTERNAL ANTISEPTICS. 69 LlTHII SaLICYLAS.— IT. S — Average dose: 1 gm. (15 grains). Strontii Salicylas. — U. S. — Average dose: 1 gm. (15 grains). Pitenylis Salicylis. — U. S. — Salol (U. S. P., 1890). Average dose: 0.5 gm. (7% grains). Methylis Salicylis. — U. S. — Average dose: 1 c.c. (15 minims). Oleum Betur-ee. — U. S. — Average dose: 1 c.c. (15 minims). Oleum Gaultherije. — U. S. — Average dose: 1 c.c. (15 minims). Saliciyum. — U. S. — Average dose: 1 gm. (15 grains). The mercurials will be discussed under the sub- ject of alteratives. CHAPTER IV. GENERAL TONICS. Tonics are defined by Gould as “medicines or agents which promote nutrition and give tone to the system.” Since these conditions are met bjr any improve- ment in the general health, the use of the term is often an admission of our want of exact knowledge of the mode of action of the drugs or remedies so classed. Strychnin increases the reflexes and may thus improve the muscular tone. Bitters may increase the impaired appetite and digestion, which will, of course, improve the general condition, hence these agents may be spoken of as tonics ; and, if we were not acquainted with the organism which causes malarial fever, and with the effect of quinin on that organism, but merely knew that this condi- tion was relieved by quinin, we would be justified in attributing the action to the tonic effect of quinin. Therefore, as our knowledge of the exact mode of action of the various remedies of this group increases, the importance of the term itself will correspondingly decline. Among the tonics we may include stomachics, hematinics, or agents which assist in the regen- eration of blood, including iron, arsenic, codliver oil and hypophosphites, and the alteratives, the mode of action of which is unknown. HEMATINICS. 71 HEMATINICS. Ordinary food is the most important of the hem at ini cs, if, indeed, we have any others which are of considerable importance, especially if we ac- cept the definition which includes iron in any as- similable form as food. iROisr. Most of the iron in the body, amounting to from 2y 2 to 3 grams, (38 to 45 grains), occurs as a con- stituent of hemoglobin, an extremely complex sub- stance in which the iron is much more firmly bound than in the ordinary iron albuminate. In addition to that found in the blood, iron is an im- portant constituent of the body cells, though pres- ent only in very minute quantity. The animal body is generally supposed to be in- capable of building up complex organic molecules from elementary substances, and it seems more than probable that all the iron in the hemoglobin is derived from the vegetable kingdom, and that inorganic salts of iron do not take part directly in its formation, though they may influence it markedly. 1 The absorbability of inorganic iron was not questioned before the investigations of Kletzinsky, about fifty years ago, and it is even more recently that the subject began to attract considerable at- tention, but the literature at the present time is rather extensive and many contradictory results have been obtained. It is perfectly obvious that iron as it exists in 1. Prior to the discovery of Wohler of the synthesis of such a comparatively simple substance as hippuric acid in the kidney, it was supposed that no synthesis could occur in the animal body. 72 PHARMACOPEIA AND PHYSICIAN. vegetables is capable not only of being absorbed, but of being utilized in the formation of hemo- globin, and it is only when the appetite or diges- tion is greatly impaired that there can ever exist any marked deficiency in the supply of iron, only about 10 milligrams (1/6 grain) being required daily under ordinary conditions, but there may arise the necessity for a stimulation of the function concerned in the utilization of the iron taken in the food; if inorganic iron stimulates this func- tion, and it apparently does under certain condi- tions, then it acts as a medicine. Many efforts have been directed toward deter- mining whether ' iron, other than that existing in the food, is absorbed from the alimentary canal. Attempts to measure the difference between the amount ingested and that excreted proved incon- clusive. Iron is probably excreted into the intes- tine after absorption, though Tartakowsky doubts if the iron found in the intestinal epithelium is in course of excretion, and the amount excreted often considerably exceeds that administered. Microchemic means have been employed to solve the problem, and A. B. MacCallum has found that only a slight degree of absorption in the first few inches of the duodenum follows the administration of small doses of inorganic iron, nearly all being precipitated by the mixed chyme, pancreatic juice and bile, but when large doses are taken absorption appeared to take place throiagh the whole length of the small intestine, while Tartakowsky found that inorganic iron was also absorbed from the rab- bit’s stomach. MacCallum found that iron, in the form in which it exists in yolk of egg, is absorbed, while HEMATINICS. 73 Marfori’s albuminate and the commercial pepton- ate seemed to stimulate the leucocytes to invade the epithelial layer of the villi in the guinea-pig, but many investigators now believe that absorption occurs mainly by way of the lymph channels and not by the blood. Since iron, like any other foreign substance, may be excreted without having been utilized after absorption, the question is not one of absorption alone, but of the form in which iron must be ab- sorbed in order that it may take part in the forma- tion of hemoglobin, and be utilized in the body cells. In addition to the food irons, the assimilation of which it is not necessary to discuss at present, certain other forms have been found capable of being converted into hemoglobin, and we may say that many physiologic chemists believe that there is no reason to suppose that inorganic salts of iron are not as readily assimilated as are the organic, and Tartakowsky does not believe that even the food irons are absorbed in the form of the complex combinations in which they exist in plants. Socin, working in Bunge’s laboratory, proved that iron, in the form in which it exists in yolk of egg (hematogen, as it is called by Bunge, who isolated it), is capable of assimilation. He fed this, and no other form of iron, to mice for a period of 100 days, during which time they gained in size and weight without becoming anemic. Bunge considers that hematogen is the un- doubted precursor of hemoglobin, but his views have not been universally accepted. Hematogen. according to the investigations that have been made by Bunge, is more stable than the combina- 74 PHARMACOPEIA AND PHYSICIAN. tions of iron that are found in vegetables and it is also more easily isolated. Schmiedeberg isolated an organic iron com- pound, which he named ferratin, from the liver, and which he considers the true precursor of hemo- globin. Ferratin may be prepared synthetically from an alkaline solution of albuminate of iron, and is usually considered merely as an ordinary albuminate, but Schmiedeberg strong^ insists that it is iron-acid-albumin, and calls attention to certain chemic differences between it and the or- dinary albuminate. Marfori isolated the com- pound containing 0.7 per cent, of iron, but as most easily prepared- it contains from 4 to 8 per cent., which strongly suggests that the precipitate carries down mechanically some other form of iron. The examples quoted serve to show the diversity of opinion among authorities as to the actual pre- cursor of hemoglobin, but the question is of less therapeutic importance than it would seem at first thought, in view of the fact that it is a compara- tively infrequent occurrence that a patient is un- able to take a sufficient amount of iron in the food. We have devoted so much space to the subject mainly because the manufacturers of certain nos- trums, used as hematinics, are prone to quote such results as those obtained in Bunge’s laboratory only so far as they show that organic iron prepara- tions are assimilable while the inorganic are not, but we have not yet seen any mention made in the free circulars of the statement made by Bunge that inorganic iron does stimulate the functions concerned in the assimilation of iron when it is abundant in the food, and that organic iron pre- hem Any IC\S. partitions are without beneficial effect under sim- ilar conditions. This, however, is of the very greatest importance from a practical point of view, because- we can nearly always select a suitable diet containing an abundance of iron, and organic iron in any other shape is, therefore, seldom if ever recpiired. As evidence of the role played by inorganic iron we may mention the results obtained by Abder- halden. He found that the iron of hematin and hemo- globin is not so readily assimilated as is that of the ordinary food. Animals were fed on a diet in which a deficiency of iron was made up by hematin and hemoglobin, and they did not thrive so well as those which received food containing a suffi- ciency of iron, though those which received hema- tin and hemoglobin did thrive better than those in which the deficiency was made up by an inorganic iron. This might be easily considered as conclu- sive proof of the value of organic iron nostrums, but when we repeat that it rarely happens that the patient can not take food containing an abundance of iron -the fact loses most of its significance. When the food was rich in iron the addition of hematin and hemoglobin (which may be consid- ered the best type of organic iron) had no effect on the assimilation of the food iron, but when in- organic iron was added to such iron-rich food the assimilation was stimulated . 2 2. Cushny : “Pharmacology and Therapeutics” says : “The words organic and inorganio in connection with these prepara- tions have no reference' to the combination to which iron is attached, hut to the method of attachment. Thus the acetate and albuminate of iron are both classified among the inor- , ganic iron compounds, because they are capable of dissocia- 76 PHARMACOPEIA AND PHYSICIAN. When inorganic iron is added to the food or to organic iron, it combines with, the hydrogen sul- phid in the intestine and spares the organic iron from precipitation. Inorganic iron should thus prove beneficial even if Schmiedeberg were cor- rect in contending that inorganic iron is not ob- sorbed from the intestine except after corrosion of the mucons membrane. He claims that corrosion occurs even when such a salt as ferric chlorid is administered after free dilution, because the water is rapidly absorbed, leaving the salt in concen- trated solution. Other investigators have also called attention to the corrosive action of hydrochloric acid when liberated from a metallic salt in contact with the tissues, and it may be found that the ferrous sul- phate or carbonate may be found to be preferable to the more widely used ferric chlorid. OFFICIAL PREPARATION'S OF IRON - . ' The list of official preparations of iron is a long one and comprises a number of substances that are not generally used as hematinics. The use of the salts of iron as astringents will be referred to in Chapter Y, and need not be tion, and the iron is precipitated by ammonium sulphid. Masked iron is a preferable term for organic iron, but has not been so widely used. A large number of the proteid com- pounds that have been introduced in the last few years promise to be relegated to merited oblivion in the near future. The albuminate of iron and the peptonate of iron are gen- erally prepared by the action of the chlorid on egg albumin or on peptone, and differ very considerably in the percentage of iron. These preparations are not organic iron in the sense defined above, for the iron can be split off easily, and Is precipitated by sulpbids almost as readily as the ordinary salts.” HEMATINIGS. 77 considered at this time more than to enumerate the preparations that may be so used. Among the official preparations that are useful as astringents or as stypics are : LrQuoR Ferri Subsulphatis. — IT. S. — The solution of ferric subsulphate, better known as Monsel’s solution, in addition to being used as an astringent and styptic, has also been recommended as a hematinic. Average dose: 0.2 c.c. (3 minims). Probably the most widely used of the several preparations of iron, is : Tinctura Ferri Chloridi. — U. S. — This preparation contains 35 per cent, by volume of solution of ferric chlorid and should be prepared at least three months before being used. Tincture of ferric chlorid, or tincture of iron, as it was for- merly called, has long been considered one of the most efficient of the inorganic iron preparations. Average dose: 0.5 c.c. (8 minims). Ferri Sulphas and Ferri Sulphas Granu- latus. — U. S. — These differ only in the size of the crystals ; they consist of ferrous sulphate contain- ing 7 molecules of water of crystallization. Ferrous sulphate is soluble in less than one part of water, hut is insoluble in alcohol. Average dose: 0.2 gm. (3 grains). Ferri Sulphas Exsiccatus. — U. S. — Exsic- cated Ferrous Sulphate is a grayish-white powder that is slowly but completely soluble in water. About 65 grams of the exsiccated preparation are equivalent to 100 grams of the granulated. Average dose: 0.12 gm. (2 grains). Pilule Aloes et Ferri. — U. S. — Each pill contains 0.07 gm. (about 1 grain) each of exsic- PHARMACOPEIA AND PHYSICIAN. cated ferrous sulphate, purified aloes and aromatic powder. Average dose : 2 pills. PiLULiE Ferri Carbonatis. — U. S. — This preparation is variously known as Blaud’s pills, Griffith’s pills or Vallet’s pills. Each pill contains about 0.06 gm. (1 grain) of ferrous carbonate, with potassium sulphate, althea tragacanth and glycerin. Average dose : 2 pills. Ferri Carbonas Saccharatus. — U. S. — The saccbarated carbonate of iron should contain not less than 15 per cent, of ferrous carbonate. Average dose; 0.25 gm. (4 grains). Massa Ferri Carbonatis. — FT. S. — Mass of ferrous carbonate, better known as Yallet’s mass, contains nearly 5 per cent, of ferrous carbonate. Average dose: 0.25 gm. (4 grains). Misttjra Ferri Composita. — IT. S. — Com- pound iron mixture, or Griffith’s mixture, is much more popular in England than in this country. It contains freshly precipitated ferrous carbonate sus- pended in a mixture of potassium sulphate, myrrh, syrup, spirit of lavender and rose water. Average dose: 16 c.c. (4 fluidrams). Of. the several official preparations containing ferrcus carbonate the pill of ferrous carbonate, more generally known as Blaud’s pill, is probably the most efficient and most satisfactory. This pill should he freshly prepared and should not contain free or unchanged ferrous sulphate or potassium carbonate. The practice that has been adopted by some manufacturers of massing these pills with- out allowing the chemical reaction to take place is a reprehensible one, as it is not at all probable EEMATINICS. 79 that the necessary reaction will take- place as readily in the acid medium of the stomach as it would in a test-tube or mortar. Ail the preparations of ferrous carbonate have the decided advantage over the previously men- tioned preparations of iron that they are not astringent and, therefore, are not likely to cause digestive disturbances. Another preparation that is free from the ob- jectionable feature of being astringent is : Ferrum Reductum. — U. S. — Reduced Iron oc- curs as a fine grayish-black lusterless powder with- out odor or taste. It is insoluble in water and in alcohol and, therefore, is generally directed to he dispensed in powders, capsules or pills. Average dose: 0.05 gm. (1 grain). SCALE SALTS Oy IRON. Ferri Citras. — FT. S.— Ferric Citrate occurs in thin garnet-red scales that are slowly but com- pletely soluble in water. Average dose: 0.25 gm. (4 grains). Ferri et Ammonii Citras. — U. S. — Iron and Ammonium Citrate is much more freely soluble in water than the simple citrate, and has the added advantage that it is not likely to lose this property on keeping. Average dose: 0.25 gm. (4 grains). Ferri et Ammonii Tartras. — U. S. — This occurs in thin transparent scales varying in color from garnet red to reddish brown. It is freely soluble in water but insoluble in alcohol. Average dose: 0.25 gm. (4 grains). Ferri et Potassii Tartras. — U. S. — This is 80 PHARMACOPEIA AND PHYSICIAN. very similar in physical properties to iron and am- monium tartrate. Average dose: 0.25 gm. (4 grains). Ferri et Quinine Citras. — U. S. — Iron and Quinin Citrate contains about 11.5 per cent, of quinin and ferric citrate corresponding in amount to 13.5 per cent, of metallic iron. It is slowly but completely soluble in water. Average dose: 0.25 gm. (4 grains). Ferri et Quinine Citras Solubilis. — U. S. — This preparation has practically the same compo- sition as iron and quinin citrate, but with am- monium citrate present to insure its ready and complete solubility. Average dose: 0.25 gm. (4 grains). Ferri et Strychnine Citras. — U. S. — Iron and Strychnin Citrate contains about 1 per cent, of strychnin. It is readily and completely soluble in water. Average dose: 0.12 gm. (2 grains). These several scale preparations of iron are com- paratively free from astringent properties, are gen- erally freely soluble in water, do not attack the teeth, and are not obnoxious to the taste. They are preferably directed to be dispensed in aqueous solution, with or without the addition of elixir or some other flavoring admixture. liquid preparations of iron. Yinum Ferri. — U. S. — This contains 4 per cent, of iron and ammonium citrate with syrup and white wine, flavored with tincture of sweet orange peel. Average dose: 8 c.c. (2 fluidrams). Yinum Ferri Amarum. — IT. S. — This prepara- HEMATINICS. 81 tion contains 5 per cent, of soluble iron and quinin citrate with svrup and white wine, flavored with tincture of sweet orange peel. Average dose: 8 c.c. (2 fluidrams). Glyceritum Ferri Quinine et Strychnine Phosphatum. — U. S. — The Glycerite of the Phos- phates of Iron, Quinin and Strychnin contains 8 per cent, of the soluble ferric phosphate, 10 per cent, of quinin and 0.08 per cent, of strychnin with phosphoric acid, glycerin and water. Average dose: 1 c.c. (15 minims). Syrupus Ferri, Quinine et Strychnine Phosphatum. — U. S. — This syrup contains 25 per cent, of the glycerite of the phosphates of iron, quinin and strychnin in syrup. Average dose: 4 c.c. (1 fluidram). Elixir Ferri, Quinine et Strychnine Phosphatum. — U. S. — This popular ferruginous bitter tonic contains soluble ferric phosphate, quinin and strychnin. The average dose — 4 c.c. (1 fluidram) — contains nearly 0.07 gm. (1/16 gr.) of soluble ferric phosphate, 0.035 gm. (7/12 gr.) of quinin, and 0.001 gm. (1/60 gr.) of strychnin. Average dose: 4 c.c. (1 fluidram). Liquor Ferri et Ammonii Acetatis. — IJ. S. — - This Solution of Iron and Ammonium Acetate, more popularly known as Basham’s mixture, con- tains a double salt of iron and ammonium acetate and is directed to be made by mixing 4 parts of tincture of ferric chlorid, 6 parts of diluted acetic acid, 50 parts of solution of ammonium acetate, 12 parts of aromatic elixir, 12 parts of glycerin and a sufficient quantity of water to make 100 parts. This preparation being quite dilute, is not very stable and should be freshly prepared when wanted. 82 PHARMACOPEIA AND PHYSICIAN. Average dose: 16 c.c. (4 flnidrams). There are two additional preparations of iron that, while they are not prescribed as hematinics, might well be mentioned in this connection. ANTIDOTES FOR ARSENIC. Terri Hydroxidum. — U. S. — This is the hy- drated oxid of iron of the previous Pharmacopeia and which is directed to be made by precipitating 100 parts of solution of ferric sulphate with 133 parts of ammonia water that has been diluted with 1,000 parts of cold distilled water. The resulting precipitate is directed to be washed until free from soluble sulphates. This preparation is not par- ticularly adapted for extemporaneous preparation, and, as it does not keep well, the following has been added as an efficient, extemporaneous anti- dote for arsenic : Ferri Hydroxidum cum Magnesii Oxido. — U. S. — This is directed to be made by diluting 40 parts of solution of ferric sulphate with 125 parts of water, and kept in a large well-stoppered bot- tle. The magnesia mixture is directed to be made by rubbing 10 parts of magnesium oxid with suffi- cient water to make a smooth and thin mixture, then diluting it to about 700 parts. When wanted for use the magnesium oxid mixture is to be well shaken and then gradually added to the solution of ferric sulphate and the resulting mixture again well shaken. Average dose : Arsenical antidote. 120 c.c. (4 fluidounces) . indications for iron. Hematinics are demanded when the amount of blood or of any of its essential constituents have been greatly reduced. HEMATINICS. S3 After severe hemorrhage involving the loss of less than half the blood, regeneration takes place rapidly, if the general condition of the patient is otherwise good and the food ample. In accordance with a vast amount of clinical experience and the results obtained by many inves- tigators, medicinal iron (if we may use the term) is indicated. If the patient is able to take an abundance of food rich in iron, inorganic iron alone may suffice, but if he is unable to digest such food, then hematin and inorganic iron should both be given. Iron has long been used in chlorosis, and ex- perience has shown that it is more useful in those forms of anemia in which the loss of hemoglobin is greater than that of red blood cells; in other words, when the red blood cells present, whether in normal or diminished number, are individually poor in hemoglobin. As to the form of iron to be given, of first im- portance is the selection of food. Reference to the table given below, selected from Bunge’s Plrysi- ology , 3 will enable the physician to compute ap- 3. The following table, taken from Bunge’s Physiology, gives the iron content in milligrams per 100 grams of the dried substance. Such substances as grapes will evidently yield but little iron, since they consist mainly of water : Sugar 0.0 Cabbage (dark green White of egg 0.0 leaves) 17.0-30.0 Rice 1.0-2. 5 Almonds (blanched) .... 4.9 Barley (hulled) 1.4-1. 5 Almonds (whole) 9.5 Barley (whole) 4.5 Grapes (Malaga) 5.6 Oranges 1.5 Potatoes 6.4 White bread (wheat) ... 1.5 Peas 6. 2-6.6 Apples 1.9 Beans (white) 8.3 Cow's milk 2.3 Carrots 8.6 Human milk 2. 3-3.1 Dandelion leaves (used Figs 3. 7-4.0 as salad) 14.3 Hazel nuts (blanched) . . 4.3 Beef 16.9 Hazel nuts (whole) 12.7 Asparagus 20.0 Rye 3. 7-4. 9 Yolk of egg 10.0-24.0 Cabbage (etiolated) .... 4.5 Spinach 33.0-39.0 Cabbage (light green Blood of swine 226.0 leaves) 5.6 84 PHARMACOPEIA AND PHYSICIAN. proximately the amount of food iron which the patient is receiving, and by computing the daily normal loss at 10 milligrams he can see about how much of this is left for the regeneration of hemo- globin. The figures given are for dried material, and it is to be remembered that green vegetables may lose 75 per cent, or more of their weight on drying, while fatty substances (nuts) will lose but little. If the food contains an insufficiency of iron hematin should be added, but if the food supply is abundant one of the inorganic forms of iron will prove beneficial. In our choice of medicinal iron we must be guided by the individual case in select- ing the one which causes the least disturbance of the digestion. In the absence of fever it will sel- dom occur that the patient can not take a selected diet containing an ample supply of iron. If the appetite and digestion are deficient stomachics are indicated. Inorganic iron very often gives better results in the first few weeks of the administration than it does later, which may possibly be explained by its interference with the digestion — a matter to be guarded against carefully. Large doses, if they do not disturb the digestion, are often required. Bunge distinctly warns the physician against using high-priced pharmaceutical preparations of iron and calls attention to the advantage of beef, blood sausage and blood. While warm blood may be tolerated by some in- dividuals, the aversion to it is frequently uncon- querable and hematin seems to be equally service- able in any case. 4 4. A practical method for the economic preparation of a hematin product was described by Torald Sollmann, in the Am. Jour, of Phar., June, 3 902, p. 275. HEMATINICS. 85 The etiology of some of the anemias is so ob- scure that treatment must be mainly empirical, but we may feel reasonably certain that we shall do more harm than good if we depend on the nos- trums so glowingly advertised instead of directing our efforts toward improving the appetite and di- gestion. The selection of a proper diet, together with proper doses of inorganic iron in most cases, or of organic and inorganic iron in comparatively few cases in which they are needed, will usually be found to he all that is required. When iron tends to cause constipation laxatives must be employed, preferably one of the prepara- tions of cascara sagrada, or the pills of aloes and iron, one of which may be given three times daily. As examples of the innumerable combinations in which iron may be prescribed we give the follow- mg: R. Ferri sulphatis exsic 3i 4| Extracti nucis vom. Extracti rhamni pursh, aa. . . . gr. xv l| M. Ft. pil. no. lx. Sig. : One pill half an hour after meals. Beduced iron or ferric citrate, may be substi- tuted for the dried ferrous sulphate, and a slightly larger amount of aloes (20 grains — 1.3 gm.) can be used in place of the extract of cascara Sagrada. Clinical experience seems to show that a formula of this kind is not so useful in those conditions in which there is a deficiency of hydrochloric acid in the gastric secretions; in such cases small doses, from half to one tea-spoonful, of the solution of iron and ammonium acetate may be given, after meals. This preparation rarely gives rise to con- stipation or other symptoms of indigestion. 86 PHARMACOPEIA AND PHYSICIAN. The pills of ferrous carbonate, Blaud’s pills, may be given either alone or the mass of ferrous carbonate, which is practically identical, may be used in combination with such a laxative as the extract of cascara sagrada, in the dose mentioned above. If desirable a bitter substance such as the extract of nux vomica may also be included as follows : B. Massa ferri carbonatis 3ii 8| Extracti nucis vom. Extracti rhamni pursh, aa. . . .gr. xx 1| M. Ft. pit. No. lx. Sig. : One pill half an hour after eating. Other bitter extracts, or other bitter substances, such as quinin or strychnin, and other laxatives may be substituted for those given above. A rep- resentative formula for a pill of this general com- position would be as follows : B. Ferri reducti Quininse sulphatis Aloe purifieat, aa gr. xlv 31 Strychnin® sulph gr. i 1 06 Ext. gentian q. s. Ft. mass et dividenda in pil. No. lx. Sig. : One pill three times a day, after eating. While it is true that the salt? of the alkaloids might better be substituted by the alkaloids them- selves, the amount of acid present is so small that it is really of very little moment. In this same connection it might be pointed out that the dried ferrous sulphate or the ferric citrate may be substituted for the reduced iron, or, by omitting the extract of gentian, the mixture may. be directed to be dispensed as a powder in capsules. The tincture of ferric chlorid is best given well diluted with water, a glass tube being used to pre- vent the corrosive action of the acid on the teeth, UEMATIjYICS. 87 and the mouth should then he well rinsed with water, or a dilute solution of an alkali such as lime water. The scale salts of iron, being, generally, com- binations with organic acids, are much less cor- rosive than the chlorid, or either of the sulphates, and may frequently be used with advantage in their stead. A representative formula for a simple solution of this kind would be as follows: R. Ferri et ammonii citratis 3i 4| Aquoe dest fid. 3xii 50 j Elixir q. s. ad fid. Siii 1 00 j M. Sig. : One teaspoonful three times a day, before eating. Any one of the soluble scale salts of iron can be substituted for the iron and ammonium citrate, and one of the aromatic waters can be used in place of the distilled water, or of the water and the elixir. The bitter wine of iron, given a few minutes before meals, is an excellent ferruginous stimulant of the appetite and digestion which women will usually find acceptable. MANGANESE. Manganese is not absorbed from the alimentary canal after ordinary doses, hence it acts as a hema- tinic only in so far as it spares iron by uniting with the sulphur which occurs in the intestines in the form of compounds. Manganese would, therefore, hardly deserve con- sideration here if it were not for its widespread use, thanks mainly to the skillful and none too scrupulous methods often employed in the exploit- ation of certain nostrums containing it. 88 PHARMACOPEIA AND PHYSICIAN. It is not probable that manganese possesses any advantage whatsoever over the numerous official preparations of iron. The so-called peptonized manganese prepara- tions, generally solutions of peptone to which some salt of manganese has been added, may be obtained from reputable dealers in chemicals, or may be made by any retail pharmacist who has the neces- sary educational qualifications to conduct even the very simplest chemical experiments. A mixture containing peptone, iron and man- ganese, and one that in many respects is superior to the preparation so extensively sold to the laity, in this country, as “Peptomangan — Gude,” has been included in the new edition of the National Formulary, now in press. When it is desired to use a' simple solution of manganese peptonate, it may be prescribed as follows : IJ. Mangani peptonati 3v 20 1 : Syrupi aurantii oxii 50 1 Aquae dest. q. s. ad 300 1 M. Sig. : One tablespoonful after each meal. It should be remembered, however, that dry preparations of peptonates of iron or manganese do not keep well, and it will usually be preferable to have a reliable pharmacist prepare a solution, similar to the compound solution of peptonate of iron with manganese, of the National Formulary, Avhich is preserved by the addition of a small quan- tity of alcohol, with sugar and aromatics. OFFICIAL PREPARATIONS OF MANGANESE. The official preparations of manganese are lim- ited in number, and, as suggested above, are even more limited in their practical application as tonics or hematinics; they are: HEM AT IN ICS. 89 MaNGANI DlOXIDUAI PRiECIPITATUM. — U. S. — Precipitated Manganese Dioxid is a new prepara- tion that has been added to replace the formerly applied crude product. Manganese dioxid, as now official, is directed to be made from manganese sulphate and should contain not less than 80 per cent, of manganese dioxid. Average dose: 0.25 gm. (4 grains). Mangani Sulphas. — IJ. S. — This occurs as colorless or pale pink crystals that are soluble in less than one part of water, but insoluble in alcohol. Average dose: 0.25 gm. (4 grains). Potassii PermangAnas.— -TT. S. — This sub- stance has been mentioned in the chapters on dis- infectants and antiseptics. In connection with tonics or hematinics it is of interest only as the source of some of the now popular organic prepara- tions of manganese. ARSENIC. It is not positively known whether arsenic is an essential constituent of the human body or not. Segale, using penici Ilium brevicaule, with which infinitesimal quantities of arsenic may he detected, found it widely distributed in animal tissues, and Bertrand found it in eggs, particularly in the yolk. Wieser concluded that arsenic is not a constant constituent in animal and human tissues, but that it is accidentally present. When one considers the distribution of arsenic in plants, in sea water and in many springs, it is apparent that abundant opportunity occurs for its entrance into the body, and, owing to its slow ex- cretion, the organism may rarely be without traces of it. 90 PHARMACOPEIA AND PHYSICIAN. If minute traces of arsenic are essential to the well-being of the body we may be sure that the ordinary food insures an abundant supply. Gies found that those members of a litter of rabbits which received arsenic grew faster than the others, while female rabbits under its influence bore larger young. This increased rapidity of growth has been observed by some, but not all, sub- sequent investigators. In this connection the ob- servation of arsenic in the yolk of egg is at least suggestive. The toxicology of arsenic is of peculiar interest because of its frequent use with fatal effect and because the appearance of the earliest symptoms are used as a guide in the therapeutic use of the .substance. The most striking effect of acute arsenical poisoning is seen in the symptoms closely re- sembling those of Asiatic cholera, and which are explainable by the characteristic action on the capillaries, particularly those of the abdominal region. The capillaries appear to suffer a peculiar par- alysis and dilation, resulting in an enormous in- crease in permeability. The escaping plasma of the blood makes its way into the intestine and, coagulating, gives rise to the “rice-water'’ stools. The withdrawal of the blood from the rest of the body into this region and its loss, as mentioned, causes the usual symptoms of collapse. The direct effects on the heart are too slight in such cases to be considered as important, and the corrosive action of arsenic is too slowly developed to be concerned in the immediate effects just de- scribed, which rapidly follow the absorption of a HEMATINICS. 91 poisonous dose. When the poisoning is more slow- ly developed, however, as after frequently repeated smaller doses, catarrh of the gastrointestinal tract is seen and fatty degeneration of various organs takes place, the picture somewhat resembling that seen after phosphorus poisoning. Even therapeutic doses frequently repeated give rise to effusion of liquid, commonly noticeable in the swollen eyelids. Arsenic is said to be capable of increasing the number of erythrocytes in anemia through its action on the bone marrow, but Engel found no in- crease in the mature red blood cells in anemia; other observers failed to see any change in the red blood cells or in the hemoglobin, though it is ac- knowledged that the bone marrow is stimulated to unusual activity. It has been claimed that arsenic actually dimin- ishes the number of red blood cells in chlorosis without altering the total amount of hemoglobin. It has been suggested that the influence of ar- senic on metabolism is due to alternate reduction and oxidation, arsenous and arsenic acids being re- peatedly formed, but this seems hardly probable. OFFICIAL PREPARATION S OF ARSENIC. Arseni Trioxidum. — U. S. — Arsenic Trioxid was formerly official as Aeidum Arsenosum. It consists of not less than 99.8 per cent, of pure arsenic trioxid. It may occur in transparent masses, like glass or in opaque masses resembling porcelain; more frequently, however, it is found as an odorless and tasteless white powder that is slowly but completely soluble in 100 parts of water but very sparingly soluble in alcohol. The pres- 92 PHARMACOPEIA AND PHYSICIAN. ence of either alkalies or halogen acids facilitates the solution of arsenic trioxid, and this fact is taken advantage of in the preparation of the sev- eral official solutions. White arsenic, as it is still called, was not known in Europe until some time after the eleventh century. It was scarcely well defined until 1733, when Brandt accurately deter- mined its nature and leading chemical properties. Average dose': 0.002 gm. (2 mg. or 1/30 grain). Arseni Iodidum. — U. S. — Arsenous Iodid oc- curs as an orange red, inodorous crystalline pow- der. It is soluble with partial decomposition, in about 12 parts of water and in about 28 parts of alcohol. Average dose: 0.005 gm. (5 mg. or 1/10 grain). Sodii Arsenas. — IT. S. — This occurs as color- less, transparent odorless prisms that are soluble in less than two parts of water, but very sparingly soluble in alcohol. Average dose: 0.005 gm. (5 mg. or 1/10 grain). Sodii Arsenas Exsiccatus. — IT. S. — This should contain not less than 98 per cent, of pure anhydrous di-sodium-ortho-arsenate. It occurs as an amorphous white powder, permanent in dry air ; it is soluble in about three parts of water and is practically double the strength of the hydrous or crystalline preparation mentioned above. Average dose: 0.003 gm. (3 mg. or 1/20 grain). SOLUTIONS OF ARSENIC. While several of the preparations of arsenic ap- pear to have been used from time immemorial as topical applications, the internal use of arsenic, in Europe, appears to date from the introduction of the solution of potassium arsenite, popularly HEMATINICS. 93 known as Fowler’s solution, about 1786. During the following decades a number of modifications of this solution of arsenic were suggested by medical practitioners and apothecaries, all of which had, or were supposed to have, some distinctive proper- ties. Of these almost innumerable solutions that have been proposed during the past century, the following are now official : Liquor Potassii Arsenitis. — U. S.— The Solu- tion of Potassium Arsenite, universally known as Fowler’s solution, as noted above, was the first of the several solutions to be used and is even now the most popular, being known in every civilized country in the world. Solution of potassium arsenite contains the equivalent of 1 per cent, of arsenic trioxid, with a sufficient amount of the compound tincture of lavender to give the preparation a distinctive color and flavor. Average dose: 0.2 c.c. (3 minims). Liquor Acidi Arsenosi. — IT. S. — This Solu- tion of Arsenous Acid contains the equivalent of 1 per cent, of arsenic trioxid, with 5 per cent, of diluted hydrochloric acid. This preparation was introduced about the end of the eighteenth cen- tury by Dr. De Yalanquin, in London ; it was the first of the several acid preparations of arsenic. Average dose: 0.2 c.c. (3 minims). Liquor Arseni et EEydrargyri Iodidi. — TJ. S. — This preparation, more popularly known as Donovan’s solution, contains 1 per cent, each of arsenous iodid and mercuric iodid. Average dose: 0.1 c.c. (l 1 /^ minims). Liquor Sodii Arsen atis. — IT. S. — This Solu- tion of Sodium Arsenate, also known as Pearson’s 94 PHARMACOPEIA AND PHYSICIAN. solution, contains 1 per cent, of exsiccated sodium arsenate. Average dose: 0.2 c.c. (3 minims). THERAPEUTICS OP ARSENIC. While the probability of favorably influencing nutrition under certain conditions, by means of the action of arsenic on the capillaries can not be doubted, its therapeutic use for such purposes is empirical. The use of arsenic as a local caustic has a rational basis, but that -will not be discussed here. Arsenic has long been used in the treatment of a great variety of complaints in which anemia is a prominent symptom. Among these conditions is remittent fever, in which it is given in connec- tion with quinin. It is preferable to give the two separately, arsenic being used in the form of the solution of potassium arsenite, which has a wide range of pharmaceutic incompatibility, being vir- tually an alkaline solution. This solution may be given in large doses — ten drops — gradually re- duced, or in small doses rapidly increased until in- testinal symptoms or swelling of the eyelids is seen, after which the drug is to be discontinued for a time, and then given in doses of from three to five drops three times a day. It is of importance that the dosage be watched so that no serious dis- turbance of digestion may occur. The frequently made suggestion to combine preparations of opium with the preparation of arsenic, so as to establish a tolerance for the latter, is one that is of doubt- ful utility in view of the fact that opium would be likely to mask the symptoms that occur as fore- runners of more serious disturbances. HEMATINICS. 95 In chlorosis, arsenic seems to be useful in con- nection with iron. The combination most fre- quently prescribed is a pill of ferrous carbonate with arsenic trioxid. For this purpose the latter may be combined with the official pill, or the mass of ferrous carbonate, as follows : IJ. Mass® ferri carbonatis . 3i 4| Arseni trioxidi gr. i 1 05 M. et div. in pil No. xl. Sig. : One pill three or four times a day. Pernicious anemia may show some temporary improvement under arsenical treatment, but the effect is not permanent. It has been said that lymphosarcoma has shown improvement under its use, and the following con- ditions are enumerated among those in which it has been employed: Dyspepsia, diseases of the skin dependent on nutritional derangements, cachetic conditions resulting from diabetes, tuber- culosis and a number of other more or less well- defined diseases. The use of arsenic among veterinary surgeons for improving the appearance of horses by in- creasing the glossiness of the hair and adding to the fat under the skin is well known. PHOSPHORUS. Phosphorus, in both inorganic and organic com- bination, is widely distributed in the body. Leci- ithin, a compound of cholin with phosphoric and fatty acids, occurs in nearly all living animal and vegetable tissues, while the nucleins, which are also rich in phosphorus, are likewise widely dis- tributed. While some observers have found that when lecithin or nuclein was added to the food of ani- 96 PHARMACOPEIA AND PHYSICIAN. mals the latter grew faster than the controls which were not given these compounds, these results are not universally accepted as proving their value, and we have the classic research of Miescher, which proves that the animal organism is abun- dantly able to form those compounds from others normally existing in the body. Midscher found that the mass of eggs in the salmon increased from 0.4 per cent, to from 19 to 27 per cent, of the total body weight during some months when the salmon took no food, while the muscles showed a corresponding loss in weight. Much more nuclein and lecithin are found in the eggs than previously existed in the muscle, which, however, are rich in other phosphoric-acid com- pounds, probably potassium salts which are loosely bound to the proteid. Miescher concludes, and the evidence seems in- controvertible, that the newly formed combinations characteristic of the egg (including lecithin and nuclein) are formed by chemic action from the albumin, fat and phosphates of the muscle. It will be readily seen how the makers of nos- strums can use such results as those quoted in re- gard to the action of lecithin in causing an in- crease in the body weight, while the much more important and generally accepted results of Mies- eher are ignored. Phosphorus and its preparations might be omit- ted without serious detriment to this chapter, but for the fact that they have been so widely used and therefore require at least a passing notice, particularly as the toxicology of phosphorus is of considerable interest. HEMATINIGS. 97 The heart suffers greater direct injury in phos- phorus poisoning than does any other organ, while the accumulation of fat which it causes in the liver is apparently an infiltration, resulting from a peculiar disturbance of metabolism rather than the result of any change in the organ itself. Hemorrhages may occur from degeneration of the capillary walls, while a similar effect on the mucous membranes of the stomach and intestine causes pain, vomiting and diarrhea. Minute doses of phosphorus, long continued, in- duce a peculiar change in the growth of the bones in the young, leading to the deposition of dense bone where cancellous is being formed, or the change of the latter, when already formed, into the compact form. The phosphates are of the very greatest im- portance in the plant and animal bodies, but they occur so abundantly in the soil and in ordinary food that there is seldom any deficiency in the sup- ply, and any want of them in the human body must be due to the inability to use that which is offered. Schmiedeberg calls attention to the for- mation of the egg shell as evidence of the great capacity of the animal organism to supply a special demand. Sollmann states that there is absolutely no scientific foundation for the popular belief that the hypophosphites improve nutrition in anemia and beginning phthisis, while Cushny states that most reliable investigators deny that they have any other influence on nutrition and digestion than that of the better known and cheaper salts of lime. 98 PHARMACOPEIA AND PHYSICIAN. soda or iron, and Schmeideberg appears to think them entirely unworthy of notice. Many clinicians, on the other hand, appear to have observed a distinct improvement in the appe- tite and digestion under the influence of the hypo- phosphites, but even if such is the case, there seems to be absolutely no reason or excuse for our employing such a high-priced, unsightly and un- scientific preparation as the muddy-looking Fel- low’s syrup, since any competent pharmacist can make a more presentable and more satisfactory preparation at a very much smaller cost. In fact, if the hypophosphites do possess any distinct me- dicinal properties, the official preparations afford an ample choice for any condition or need. OFFICIAL PREPARATIONS OF PHOSPHORUS. Phosphorus. — TJ. S. — A translucent, nearly colorless solid, having at ordinary temperatures about the consistency of beeswax. Phosphorus is nearly insoluble in water, but is soluble in 350 parts of alcohol and in 50 parts of a fatty oil. Average dose: 0.0005 gm. (0.5 mg. 1/128 grain) . Pilulh? Pilosphori. — U. S. — Each pill con- tains 0.0006 gm. (0.6 mg. 1/100 grain). Average dose: 1 pill Acidum Phosphoricum. — U. S. — This con- tains 85 per cent, of absolute orthophosphoric acid. It is usually prescribed as : Acidum Phosphoric Dilutum. — U. S. — This contains 10 per cent, of absolute orthophosphoric acid. HEMATINICS. 99 Average dose: 2 c.c. (30 minims). Phosphoric acid has many of the properties of other (inorganic) acids, and probably has no evi- dent advantage over them as a tonic. The official salts of phosphoric acid usually par- take of the properties of the base rather than the acid, and need not be mentioned in this connection. Acidum Hypophosphorosum. — U. S. — This contains 30 per cent, of absolute hypophosphorous acid and is chiefly used in preparing : Acidum Hypophosphorosum Dilutum. — IT. S.- — This contains 10 per cent, of absolute hypo- phosphorous acid. Average dose: 0.5 c.c. (8 minims). The official salts of hypophosphorous acid are : Calcii Hypophosphis. — IT. S. Potassii Hypophosphis. — IT. S. Sodii Hypophosphis. — IT. S. Average dose of any one of the above : 0.50 gm. (T 1 /) grains). Potasium hypophosphite is soluble -in about 0.5 part of water and in 25 parts of alcohol, and cal- cium hypophosphite is soluble in about 7 parts of water, but is almost insoluble in alcohol. In addition to the alkali hypophosphites, we also have official : Ferri Hypophosphis. — IT. S. — and: Mangani Hypophosphis. — IT. S. Average dose of either: 0.20 gm. (3 grains). The ferric hypophosphite is soluble in 2,300 parts of water, but is much more readily soluble in solutions of hypophosphorous acid and the alkali citrates. Manganese hypophosphite is soluble in about 7 parts of water. Syrupus Hypophosphitum. — II S. — Syrup of 100 PHARMACOPEIA AND PHYSICIAN. hypophosphites contains In 100 c.c. 4.5 gm. of cal- cium hypophosphite and 1.5 gm. each of sodium and of potassium hypophosphites. Average dose: 8 c.c. (2 fluidrachms). Syrupus Hypophosphitum Compositus. — U. S. — Compound Syrup of Hypophosphites contains, in each average dose (8 c.c. = 2 fluidrams) about 0.25 gm. (4 grains) of calcium hypophosphite, 0.12 gm. (2 grains) each of potasium hypophos- phite and of sodium hypophosphite, 0.015 gm. (% grain) each of ferric hypophosphite and of man- ganese hypophosphite, 0.008 gm. (% grain) of quinin, 0.0008 gm. (1/80 grain) of strychnin with sodium citrate, hypophosphorous acid and syrup. Average dose: 8 c.c. (2 fluidrams). Syrupus Calcii Lactophosphatis. — IJ. S. — This syrup contains in 100 c.c. about 3 gm. of cal- cium lactophosphate with free lactic . and phos- phoric acids. Average dose: 8 c.c. (2 fluidrams). The several salts of glycerophosphoric acid which are being advertised so extensively at the present time, as the active constituents of a number of nos- trums, are as yet not official. It is quite probable, however, that longer experience will demonstrate that they have absolutely no advantages over the hypophosphites or the lactophosphates, and that their widespread use at present is but a passing fad. THERAPEUTICS OE PHOSPHORUS AjS t D ITS SALTS. There is at least a rational basis for the use of phosphorus in rickets, osteomalacia and fracture of bones in which union fails to occur, since a dep- osition of lime salts in bone has been shown to re- sult from its use. HEMATINICS. 101 It must not be given in doses large enough to cause serious gastrointestinal disturbance. When we say that phosphorus or the hypophos- phites are used empirically in the following con- ditions it is not to be understood that we recom- mend them, but merely that they may possibly be worthy of a trial. Thus some clinicians have used phosphorus in a variety of nervous disorders, and the hypophosphites are very often used as general tonics. The treatment of tuberculosis by the hypophosphites has no place in modern therapeu- tics. Phosphorus is so slightly soluble in water that it was often dissolved in oil, but the phosphorated oil is no longer official. The pills of phosphorus, each containing 0.6 milligrams (1/100 grain) afford a very convenient form for administration. The compound syrup of the hypophosphites, with its eleven ingredients, including water, af- fords an example of the concessions made, by the revision committee of the Pharmacopeia, to pop- ular prejudice, and in time to come it will no doubt be relegated to its proper resting place with other polypharmacal preparations of the centuries long passed. The claim has been made that the hypophos- phites are effective only when the chemically pure salts are used; this claim, however, seems scarcely credible in view of the fact that our ordinary food contains much greater quantities of just such salts as are said to render the hypophosphites useless. From one to two teaspoonfuls of the compound syrup of the hypophosphites may be given before meals, as a stimulant to the appetite and diges- tion. Acids and acid fruits are to be avoided. 102 PHARMACOPEIA AND PHYSICIAN. The following may be taken as a type formula for an extemporaneous preparation of the hypo- phosphites : It. Calcii hypophosphis Sodii hypophosphis Potassii hypophosphis, aa 3i 4| Aeidi hyphosphor 3i 4| Aqua; dest §iv 120 [ Elixir q. s. ad gviii 250 j M. et filtra. Sig. : One or two teaspoonfuls three times a day, before eating. The elixir in this preparation may be replaced by glycerin, or an aromatic water, the combina- tion of the hypophosphites may be varied, within reasonable limits, and the hypophosphorous acid substituted by citric acid or by an alkali citrate. When desirable sufficient bitter may be added to make the medicine more palatable or to act as a bitter tonic. For this purpose the tincture of nux vomica, or one of the bitter alkaloids, may be added. COD-LIVER OIL. The consideration of cod-liver oil rightly be- longs under the subject of dietetics, as nearly all pharmacologists are agreed that it is merely a food, but it is so frequently lauded as a medicine that some mention of it is necessary in this place. On the discovery of traces of certain alkaloids or ptomains it was suggested that they possessed ex- traordinary value, but, as these substances are usually present in infinitesimally small quantities in good oil, and as there is no reason to suppose that they possess any beneficial effect whatsoever, it can not be said that the so-called fat free or tasteless cod-liver oils can in any sense of the word, represent cod-liver oil. HEMATINICS. 103 The crude dark-colored oil often contains a much larger proportion of free fatty acids than the white does, and it should, therefore, be more readily emulsified in the intestine and absorbed, but its disagreeable odor and taste render it pe- culiarly disgusting to all patients with delicate stomachs. Small doses of cod-liver oil can usually be borne, especially if it be given in the form of an emulsion, but even this is not always tolerated. OFFICIAL PREPARATIONS OF COD LIVER OIL. Oleum Morrhujs. — U. S. — This preparation is official in some of the foreign pharmacopeias as Oleum Jecoris Aselli, a name that may be useful on occasion. Cod-liver oil is a fixed oil obtained from the fresh livers of Gadus morrhuoe and of other species of Gadus. Average dose : 15 c.c. (4 fluidrams) . Emulsum Olei Morriiuje. — IT. S. — The Emul- sion of Cod-liver Oil contains 50 per cent, of the oil, with mucilage and syrup, and is flavored with oil of gaultheria. Average dose: 8 c.c. (2 fluidrams). Emulsum Olei Morrhuoe cum Hypophos- phitibus. — IT. S. — This contains 50 per cent, of cod liver oil, 1 per cent, of calcium hypophosphite, and 0.5 per cent, each of potassium hypophosphite and of sodium hypophosphite. It is flavored with oil of gaultheria. Average dose: 8 c.c. (2 fluidrams). Ccd-liver oil is often useful in anemias due to faulty nutrition and in the general debility which so often precedes tuberculosis: For this reason, perhaps, it has acquired a particular reputation in the treatment of tuberculosis. It can have no 104 PHARMACOPEIA AND PHYSICIAN. specific action on the bacillus of tuberculosis, nor on the course of the disease, except in so far as it is a readily assimilable food. It is often found to be useful in rickets. The pure oil, the emulsion, or the emulsion with hypo- phosphites may be used, the dose to be regulated according to the capacity for assimilation of the individual case. It may be added here that the petroleum oils alone, or in the form of emulsions, are wholly de- void of nutrient properties. They are mineral oils, and, therefore, non-saponifiable and can take no part in animal nutrition. ALTERATIVES. Alteratives are tonics, which, in some unknown way, favorably influence the processes of nutri- tion which have been disturbed by disease. They include hematinics, the various preparations of mercury, and many, if not all the preparations con- taining iodin, either free or in combination. A number of drugs of vegetable origin, such as sarsaparilla, were formerly classed as alteratives, but these are, for the most part, merely purgatives, or else devoid of therapeutic interest. The use of the thyroid gland in thyroid disease and in obesity, and of the newly discovered serum of Beebe in exophthalmic goiter, have a scientific basic, but the employment of iodids in rheumatism and in syphilis, and of the mercurials in the latter disease is empirical, and in this connection the pharmacology of these agents is of minor import- ance since it throws little light on their therapeu- tic applications. While the attempts to investigate the action of ALTERATIVES. 105 these agents have not led to satisfactory results, we may refer to the conclusions of J. Levi, who sought to compare the effect of mercurials and of potassium iodid on the metabolism and on the blood of syphilitics. He used potassium iodid and various organic and inorganic preparations of mercury in the second stage of the disease in 252 patients. Levi found that mercurials increase organic combustion and hasten metabolism in this condi- tion. With the gradual disappearance of the dis- ease the processes of nutrition improve, but re- lapses are frequent. He found no evidence, how- ever, of a specific influence on the micro-organism of syphilis, but according to the most recent view mercury is antagonistic to this micro-organism. If the use of mercurials be too greatly pro- longed the number of red blood corpuscles is diminished. Levi found that potassium iodid had a similar general influence on the nutrition of syphilitics. While it causes an increase in the body weight, improves the blood, and adds to the muscular strength, it retards combustion and less- ens metabolism. He explains its uses in tertiary syphilis by supposing that it neutralizes the dis- ease products without increasing organic combus- tion. Nearly all observers are agreed that the action of mercurials is almost wholly independent of the preparation chosen, the only essential for its ac- tion being that it shall be absorbed. Mercury probably circulates as an albuminate, which is sol- uble in the blood because of the excess of proteids and chlorids which it encounters there. Owing to the obscurity of many of the symp- 106 PHARMACOPEIA AND PHYSICIAN. toms of syphilis, and also to the fact that a com- paratively large number of people are not -willing to have it known to their physician that they suf- fer with so loathsome a disease, the condition is peculiarly favorable for the practice of charla- tans. While there is no disease that more ur- gently demands the skill and judgment of the specialist, there is none, perhaps, that is so fre- quently treated by incompetents and even by patients themselves. While we have always with us the humiliating spectacle of numerous nostrums ostensibly adver- tised only to the medical profession, some of them of vegetable origin and wholly worthless in syph- ilis, others consisting of one form or another of mercury and possessing few or no advantages over the old and better known official mercurials, we are also daily confronted with advertisements which disgrace our boasted civilization in that they seek to persuade the deluded victims to palter with the useless nostrums in the vain effort to treat themselves. MERCURY AND THE MERCURIALS. Hydrargyrum. — IT. S. — Mercury, or quick sil- ver, has been known from remote antiquity, and from the earliest times has played an important part, not alone in the industries, arts and supersti- tions, but also in the medical practices of the peo- ple who were acquainted with it. Even at present, this substance, in the form of preparations produced by mechanical subdivision of the mercury, is widely used for external appli- cation as well as for internal administration. Sev- eral of the preparations of mercury have been men- ALTERATIVES. 107 tioned under other headings, and we shall content ourselves, therefore, with recounting a few of the salient features of these several substances. Hydrargyrum cum Creta. — IT. S. — Mercury with Chalk, also known as gray powder, represents 38 per cent, of metallic mercury, with clarified honey and prepared chalk. Average dose: 0.25 gm. (4 grains). Massa Hydrargyri. — IT. S. — Mass of Mercury, better known as blue mass, contains 33 per cent, of metallic mercury, with glycyrrhiza, althaea, glycerin and honey of roses. An analogous prep- aration without the glycerin is frequently found in the shops under the somewhat incongruous title, “Powdered Blue Mass.” Average dose: 0.25 gm. (4 grains). The mass of mercury and the mercury with chalk are widely used as mild mercurials and are especially popular for use with children. Probably the most widely used as well as the most popular of all the preparations of mercury as an antisyphilitic is : Hydrargyri Iodidum Plavum.— U. S. — Yel- low Mercurous Iodid occurs as a bright yellow, am- orphous powder, without odor or taste, and is practically insoluble in water and in alcohol. Average dose: 0.01 gm. (10 mg. or 1/5 grain). Hydrargyri Iodidum Rubrum. — U. S. — Red Mercuric Iodid occurs as a scarlet-red, amorphous powder that is nearly insoluble in water, but sol- uble in 116 parts of alcohol; it is also soluble in solutions of the soluble iodids and in solution of mercuric chlorid. Average dose: 0.003 gm. (3 mg. or 1/20 grain). Hydrargyri Chloridum Corrosivum. — U. S. 108 PHARMACOPEIA AND PHYSICIAN. — Corrosive Mercuric Chlorid, more popularly known as corrosive sublimate, has been used by the Chinese from a very early period. It was used by the early Arabian physicians, and a process for its production was described by Geber in _ the eighth century. Mercuric chlorid occurs as colorless, rhombic crystals or crystalline masses, or, more frequently, as a white powder, and is odorless, but has an acrid and persistent metallic taste. It is soluble in about thirteen parts of water and in five parts of alcohol, more freely soluble in solutions of the alkaline chlorids. Average dose: 0.003 gm. (3 mg. or 1/20 grain). Hydrargyri Chloridum Mite. — U. S. — Mild Mercurous Chlorid, better known as calomel, has been known to some of the Eastern people from a very early period. It appears to have been introduced in Europe about the beginning of the seventeenth century. This substance occurs as a heavy white powder, without odor and prac- tically without taste, and is insoluble in water and in alcohol. Average dose as an alterative: 0.05 gm. (1 grain) . The Pharmacopeia includes several additional compounds of mercury, but as they are not used for internal administration they need not be enu- merated in this connection. USES OF MERCURIALS. Since the use of mercury as an alterative is largely limited to those conditions resulting from syphilis, either acquired or congenital, we shall at ALTERATIVES. 109 present confine ourselves to discussing its employ- ment in this way. The pathology of syphilis is very often so ob- scure that it should be treated by the specialist when possible, and the following is intended for the general practitioner who finds himself com- pelled to undertake the treatment of such cases. There are many distinct symptoms that are man- ifested by patients with a syphilitic history which fail to respond to the treatment which is commonly successful with persons otherwise healthy, but which at once disappear when mercury is given. Many authorities are opposed to any form of constitutional treatment for the first stage of syphilis because we have no specific, and the treat- ment may mask or even prevent the appearance of those symptoms which render the diagnosis abso- lutely positive, without preventing the ultimate effects of the disease, thus condemning the patient to the hardships of a long and painful course of treatment without positive knowledge of its neces- sity. Others rely on their ability to diagnose syph- ilis by the chancre and the history of the case, and proceed at once to the use of mercury. Inasmuch as it is supposed that mercury has comparatively little immediate influence on the course of the disease at this time, we should be very sure of the correctness of our diagnosis be- fore beginning a course of treatment which, to be effective, must be continued for many months, and is in itself not free from danger to the patient’s health. When the history of the case, together with the chancre, renders an immediate diagnosis certain, treatment should be instituted at once. 110 PHARMACOPEIA AND PHYSICIAN. All mercurials are irritant when dissolved and there are serious objections to all the different available methods of administration. Chief among these objections is the disturbance of digestion, which is not wholly obviated even when the mer- cury is injected hypodermically or applied by in- unction. Diarrhea is often a troublesome result, for which opium is advised, but the evils attending its use are obvious and its presence should always be suspected in nostrums containing well-known mercurials that are advertised as being guaran- teed not to cause diarrhea or other gastric disturb- ances. Mercury is eliminated by all the channels of excretion and the kidneys not infrequently suf- fer serious injury. It follows that we must try to find the method best suited to the individual case, and attention is directed to the following means of administration with some of the objections to be guarded against or at least kept in mind : It is generally agreed that since there is no es- sential difference between the action of the various organic and inorganic salts of mercury in syphilitic conditions, we should be guided in our choice of agent by the method of administration which ex- perience teaches us to he best suited to the individ- ual case. If the digestion suffers from the internal administration of mercurials, intramuscular injec- tion may be tried; if these are too painful, inunc- tion may be resorted to ; hut whatever method is followed we must be alert for the appearance of untoward effects and the diet must he the object of especial attention, one being selected which is nutritious while it is easily digested. The mercurials are to be avoided or used only ALTERATIVES. Ill with great caution in cachexia due to other causes than syphilis, as their tendency to disturb diges- tion may increase the trouble. They must be used only with the greatest cau- tion in acute nephritis, but they seem to be less deleterious in the chronic form, though here, too, their action must be carefully observed. Mercury is particularly potent for harm in pregnancy, especially in the latter months; abor- tion may occur or the child may suffer from mer- curial poisoning. For internal use either mercurous or mercuric iodid is usually preferred. The combination of mercuric chlorid with potassium iodid merely means the giving of mercuric and potassium iodids, as the reaction occurs as soon as the two substances are brought into contact. When the mercuric chlorid is used it is best given alone, in dilute so- lution, as it is incompatible with a great many substances. Mercuric chlorid may be given as follows : R. Hydrargyri chloridi eor gr. iii 1 20 Potassii iodidi gr. x 1 60 Aquae dest., q. s. ad f.*iii 100 [ M. Sig. : Ten drops in water after each meal. In- crease each dose daily by one drop until symptoms of mercurialism are noted, then reduce to one-half. This is not given as an example of the so-called mixed treatment, the dose of potassium iodid being entirely too small to be effective. An example of a prescription for mixed treat- ment would be as follows: R. Hydrargyri chloridi cor gr. i 1 60 Potassii iodidi 3ii 8| Aquae dest., q. s. ad f.Siii 100 1 M. Sig. : One teaspoonful after each meal. 112 PHARMACOPEIA AND PHYSICIAN. The object of giving the mercurials after meals is to insure the protection of the stomach, which the presence of food affords, against the irritant action of the metal. The menstruum or diluent for the prescription for mixed treatment may be varied in a number of ways. The water may be substituted by any one of the medicated waters, by elixir adjuvant, aro- matic exilir, compound tincture of gentian, com- pound syrup of sarsaparilla, or by a mixture of one or more of these vehicles ; the most important point to be guarded against is the attempt to com- bine the potassium and mercuric iodid with alka- loids in solution, as the mixture of potassium and mercuric iodids is one of the most effective of pre- cipitants for alkaloids. The characteristic effects of mercury are to be carefully watched for and when the gums become slightly tender the dose is to be reduced somewhat in amount and given but twice a day — after the morning and evening meals. It would be well to wash down the dose with milk, the proteid of which will serve to protect the stomach against the irritant action of the mercury. Mercurous iodid is not so corrosive as the mer- curic, or red iodid. and it is often given in pill form with some colloidal substance, such as ex- tract of gentian. The following is an example of this method of giving it : R. Hydrargyri iodidi flav gr. vi 1 40 Extracti gentianse gr- lx 4| M. Fiat pilulae No. lx. Sig. : One pill after eating. This dose may be gradually increased by giving two pills after the mid-dav meal, and then two ALTERATIVES. 113 twice, and finally three times a day until the symp- toms of mercurialism mentioned above are seen. The dose is then reduced, as in the case of mer- curic iodid, and given after the principal meals. The mild mercurous chlorid, or calomel, may be used, but it is so insoluble that it is impossible to regulate the amount that is absorbed. Next to the administration of mercurials by the mouth, the intramuscular injection is to be preferred, but it causes great pain and may result in abscess unless caution is observed. The addition of cocain hydro- chlorid has been recommended by some authori- ties, but we should bear in mind the danger of forming a habit which is, if anything, even more terrible than syphilis. The injection should be made by the physician, as the patient can not be trusted to do it satis- factorily. Eight milligrams (one-eighth of a grain) of mercuric chlorid, or of the unofficial mercuric salicylate , 5 is dissolved in about ten minims of normal saline solution and injected deeply into the gluteal muscle, care being taken to avoid the spot which supports the body when the patient is seated. The part should then be massaged gently and an ice bag or cold compress applied to relieve pain. The injections may be repeated two or three times a week. The inunction method is very com- monly employed in the establishments at Hot Springs, Ark., where many syphilitics are treated. The inunction may be done as follows : After 5. Six grains (0.4 gms.) of mercuric chlorid to the fluid ounce (30 c.c.) will equal % grain (8 milligrams) in ten minims. 114 PHARMACOPEIA AND PHYSICIAN. inducing diaphoresis, 3 grams (about 45 grains) of mercurial ointment are rubbed into the skin, not on it, daily. As this must be applied to a rather large extent of surface it is customary to select six regions which are utilized on successive days, returning on the seventh day to the first region. These are the adductor surfaces of the thighs (the most convenient when the patient is to rub the ointment into his person), the armpits and the regions just below, extending anteriorly, and the sub-scapular regions of each side. The ointments of the oxids of mercury and the oleate of mercury are more irritant than the mer- curial ointment or the blue ointment, as the di- luted mercurial ointment is now called. Too much stress can not be placed on the neces- sity of giving close attention to the various bodily functions during the mercurial treatment to main- tain the appetite and digestion unimpaired, to reg- ulate the bowels and to secure scrupulous cleanli- ness of the body. The mouth should be the object of especial attention ; carious teeth should be filled and the mouth and teeth kept thoroughly cleaned. THE IODIDS. The use of the iodids, like that of mercury, is well established on clinical evidence and we can only speculate as to the wa3 r in which it produces its effects in syphilis, chronic rheumatism and asthma. OFFICIAL PREPARATIONS. Iodum. — U. S. — Iodin occurs in bluish-black rhombic plates that have a metallic luster, a dis- tinctive odor and a sharp and acrid taste. It is only slightly soluble (1/5,000) in water, but is ALTERATIVES. 115 readily soluble in ten parts of alcohol. It is also soluble in an aqueous solution of potassium or of sodium iodid. Iodin was discovered about 1812 by Courtois, a French manufacturing chemist, but it was not used in medicine until after 1820, when its medic- inal virtues were first made known by Dr. Coin- det, Sr., of Geneva. Average dose: 0.005 gm. (5 mg. or 1/10 grain). Liquor Iodi Compositus. — U. S. — Compound Solution of Iodin contains 5 per cent, of iodin and 10 per cent, of potassium iodid in distilled water. Average dose: 0.20 c.c. (3 minims). Tinctura Iodi. — U. S. — Tincture of Iodin, as now official, represents an alcoholic solution of 7 per cent, of iodin and 5 per cent, of potassium iodid. The resulting tincture is freely miscible with water and with alcohol. Average dose: 0.10 c.c. (1% minims). Acidum Hydriodicum Dilutum.— U. S. — This is a new addition to the Pharmacopeia and is in- tended primarily for the preparation of the syrup of hydroidic acid. It should contain not less than 10 per cent, by weight of the absolute acid. Average dose: 0.50 c.c. (8 minims). Syrupus Acidi Hydriodici. — U. S. — This is a clear, colorless, syrupy liquid that contains about 1 per cent, of absolute hydriodic acid. Average dose: 4 c.c. (1 fluidram). Attention may here he called to the fact that some of the manufacturers of so-called permanent syrup of hydriodic acid have taken advantage of the fact that glycerin is less susceptible to chemic change with hydriodic acid than syrup, and are, therefore, offering a gylcerite or hydriodic acid 116 PHARMACOPEIA AND PHYSICIAN. under the name of syrup. While it can not be definitely proved that this substitution is a danger- ous practice, it is, nevertheless, one of the little dishonesties that are so frequent in other lines of trade and should not he countenanced in connec- tion with the production or the use of medicinal substances. Syrupus Ferrt Iodidi. — U. S. — This syrup, in harmony with the Brussels conference agreement, now contains about 5 per cent, by weight, of fer- rous iodid. Average dose: 1 c.c. (15 minims). The official salts of iodin are all freely soluble in water and are also soluble in alcohol and alco- holic liquids. They are, in the order of their pop- ularity and use: POTASSII IODIDUM. — IT. S. SoDII IODIDUM. — U. S. SlRONTII IODIDUM. — U. S. Average dose of any of the above : 0.50 gm. (7i/j grains). Ammonii Iodidum. — U. S. Average dose: 0.25 gm. (4 grains). While mercury is employed in all stages of syphilis, but is most useful in the second stage, the iodids are employed in the second and third stages, but find their greatest field of usefulness in the third. The iodids enjoy a peculiar reputa- tion in the treatment of those symptoms of tertiary syphilis, such as periostitis, which are manifested in connection with the bones. Bronchitis, in those who suffer with a rheumatic or gouty diathesis, often shows greater improve- ment under the influence of this drug than with any other treatment. ALTERATIVES. 117 The ioclids are rarely used alone in the second stage of syphilis, hut in combination with mercury, known as the mixed treatment, already referred to, they appear to be of value. There can be no doubt of the usefulness of the iodids in relieving the symptoms occurring in the third stage of syphilis, and we have few therapeu- tic facts which are better attested. The saturated solution of potassium iodid is, perhaps, the most commonly used form of admin- istration. The preparation of this may be entrusted to the pharmacist or it may be ordered as follows : R. Potassii iodidi si 30 1 Aqu® dest. q. s. ad fgi 30 1 M. Ft. solut. Sig. : Five drops after eaclr meal, the dose to be increased by one drop each day. The increase in the amount to be taken may be continued until the symptoms of iodism arise or until sixty or more drops are taken daily. The patient is to be instructed as to the symp- toms to be expected, such as pain in the region of the parotid gland, etc. We are as far from being able to explain the action of the iodids in chronic rheumatism and asthma as in syphilis, but their usefulness is indis- putable and unquestioned. It is of little consequence whether we choose potassium iodid or one of the other inorganic iodids or an organic preparation. Potassium iodid has long been the most popular of all of the avail- able preparations and will probably continue to be the most useful or, at least, the most frequently used. 118 PHARMACOPEIA AND PHYSICIAN. THYROID GLAND. When it was found that the feeding of thyroid substances would obviate the symptoms which or- dinarily follow the removal of that gland, the sug- gestion was made that it might be effective in com- bating the symptoms associated with disease of the gland. This was found to be true, and the fact that. the substance is effective when given by the stomach at once suggested that there must he some active principle found in the gland. This principle, called iodothyrin, containing 9.3 per cent, of iodin, possesses the same therapeutic prop- erties as the gland substance; under its uses a great increase in metabolism occurs, superfluous fat disappears and an increased combustion of proteid takes place, explaining its use in obesity and the necessity for a diet rich in proteid when this substance is used for such conditions as myxe- dema. G-landulje TiiYROiDiE Siccae. — U. S. — Des- iccated thyroid gland is officially described as “the cleaned, dried and powdered thyroid glands of the sheep, freed from fat.” It occurs as a yellowish amorphous powder, having & peculiar odor; it con- tains the active ingredients of the thyroid tissue. It is partially soluble in water. Average Dose: 0.25 gm. (4 grains). Thyroid gland or iodothyrin is indicated in obesity, after removal of the thyroid or when the latter, through disease, fails to function properly, as in myxedema and in hypoplastic follicular goi- ter. STOMACHICS. In this group are included a number of agents, many of them used for centuries, with actions STOMACHICS. 119 scarcely better understood now than they were in the remote past. They include those agents com- monly called bitters and aromatics, terms which refer only to taste, or, to be more accurate in the case of aromatics, to taste and smell, but which are employed as therapeutic terms for want of better, thus showing how little we know of their mode of action. Despite this want of exact know- ledge of their pharmacologic action, the accumu- lated clinical evidence of 2,000 years or more goes to show that they are useful in slight catarrhal conditions and in minor functional disturbances of the alimentary canal in which there are no ser- ious anatomic changes. It is possible that their beneficial influence is sometimes due in part to the physic effect, as they are agreeable to many tastes, and their regular use may encourage the patient — two important factors in digestion. Most of the experiments that have hitherto been conducted with these agents have been made on animals, and the results have been variable and often contradictory, hence we must depend almost entirely on clinical evidence for guiding us in their uses. Owing to the great variability of the functions involved and the natural discrepancy in the capa- bility of various observers, most inaccurate conclu- sions are reached, and, therefore, no attempt can be made to give precise information as to the exact relative merits of one member rather than another in a given condition. Bidder and Schmidt, in 1852, observed that the sight of food caused the secretion of gastric juice in 120 PHARMACOPEIA AND PHYSICIAN. a fasting dog, and Pawlow, in 1888, proved the existence of specific secretory nerve fibers in the vagus, and that the gastric secretion is stimulated reflexly from the mouth. That the taste of bitter substances excites the flow of saliva is common ex- perience, and they are said to stimulate reflexly the gastric secretion when they are taken in the mouth. It has not been proved that the bitters have any effect on pancreatic secretion in animals, but it is probable that they do stimulate it reflexly in man. Borissow has recently studied the effects on gas- tric secretion in the dog of bitter substances taken into the mouth but not into the stomach. He found that the bitter taste caused a marked in- crease beginning almost immediately, but not last- ing long. He therefore advises that the substance, preferably in liquid form, be given only a short time before eating. He maintains that the nega- tive results obtained by Tschelzow were due to the use of excessive amounts of bitter extract which in- hibit the digestive action. Bitter substances which pass into the stomach without producing a bitter taste are probably without effect on the appetite and digestion. Bitter substances in the stomach have been found to increase the number of leucocytes in the blood, and, according to Hofmeister, the leucocytes are concerned in the transportation of a part of the di- gestive proteids into the circulation. The bitters, therefore, should cause a more rapid absorption of the digested proteids. It can not be stated posi- tively whether or not the bitters increase the gas- tric movements, but it has been suggested that in- creased functional activity of the gastrointestinal canal may occur from reflex stimulation, due to STOMACHICS. 121 irritation of certain sensory nerves in the stomach, in a manner analogous to the reflex stimulation of the gastric secretion by the taste or sight of food. After therapeutic doses of the simple bitters have reached the stomach they can hardly exert any perceptible effect directly on the activity of the gastric juice, and this extremely slight effect, if adverse, would be very much more than counter- balanced by the increased amount of the secre- tion. While there are a number of official substances that may he, and are, used as simple bitters or stomachics, it will not be necessary to enumerate more than a few of the more popular to illustrate the variety and the uses of this class of drugs. Gentiana. — U. S. — The dried rhizome and roots of Gentiana lutea, constitute by far the best known and the most widely used of all simple bit- ters. This drug is not alone of interest medicin- ally, but it has also taken an important part in the folklore, traditions and legends of European peo- ples. It is said to have been introduced into med- icine by Gentius, King of Illyria, who first discov- ered its medicinal virtues. Fluidextractum Gentian.®. — U. S. — This is made with diluted alcohol. Average dose: 1 c.c. (15 minims). Entractum Gentians. — IT. S. — This is an aqueous extract of gentian evaporated to pilular consistence. Average dose: 0.25 gm. (4 grains). Tinctura Gentian.® Composita. — IT. S. — This represents 10 per cent, of gentian, 4 per cent, of bitter orange peel and 1 per cent, of cardamom in 60 per cent, alcohol. 122 PHARMACOPEIA AND PHYSICIAN. Average dose: 4 c.e. (1 liuidram). 6 Calumba. — U. S. — The dried root of Jateorhiza palmata was introduced into Europe by the Portu- guese in the seventeenth century and has been much employed as a simple bitter since that time, particularly on the continent of Europe. Fluidextractum Calumba. — TJ. S. — This is made with 70 per cent, alcohol. Average dose: 2 c.c. (30 minims). Tinctura Calumba. — TJ. S. — This represents 20 per cent, of the crude drug. Average dose: 4 c.c. (1 liuidram). Quassia. — TJ. S. — The wood of Picarasma ex- celsa — Jamaica quassia or of Quassia amara — Sur- inam quassia, appears to be more popular in Eng- land than in this country. The official prepara- tions are: Fluidextractum Quassi-E. — TJ. S. — This is made with 33 per cent, alcohol. Average dose: 0.5 c.c. (8 minims). Extractum Quassi-E. — TJ. S. — This is an aque- 6. The compound tincture of gentian is probably the most popular of all stomachics and is widely used either alone or in combination with a mild antacid, such as sodium bicar- bonate. A mixture that is largely used, particularly in hos- pital practice, may be compounded somewhat as follows : R. Tinct. gent, comp 3x 40 Sodii bicarb gr. xc 6 Aquae q. s. ad 3iii 100 To be given in doses of 2 or 3 teaspoonfuls before meals. Such a prescription, of course, may be varied in innumer- able ways, the addition of compound tincture of cardamom will not alone improve its appearance, but will also make it much more acceptable, in that it makes the whole mixture more aromatic. The addition of tincture of capsicum, 0.2 c.c. or 0.3 c.c. (3 to 5 minims) to each dose, makes the mixture sharp and pungent and may be desirable, particularly in' cases of alcoholic gastritis. STOMACHICS. 123 ous extract of quassia, representing ten times its weight of the crude drug. Average dose: 0.05 gm. (1 grain). Tinctura Quassia. — U. S. — This represents 20 per cent, of quassia in 35 per cent, alcohol. Average dose: 2 c.c. (30 minims). Two other drugs which are frequently used by American physicians are chirata and berberis. Chirata. — U. S. — The dried plant of Swertia Chirayita is a comparatively recent addition to European medicine, though it has long been used and held in high esteem by the Hindus. The only official preparation in our Pharmacopeia is : Fluidextractum Chiratae. — U. S. — This is made with diluted alcohol. Average dose: 1 c.c. (15 minims). Berberis. — IT. S. — (Barberry) — The rhizome and roots of Berberis aquifolium. Fluidextractum Berberis. — IT. S. — This is made with diluted alcohol. Average dose: 2 c.c. (30 minims). AROMATICS. Aromatics contain volatile oils, on which they de- pend for their flavor and for a slightly irritant ac- tion on the mucous membranes. Brandi found that the irritation and the consequent hyperemia of the mucous membrane of the alimentary canal, due to sharp tasting substances, caused increased absorption of certain products of digestion. As the aromatics usually have an agreeable taste, they probably increase gastric secretion by reflex stimu- lation, but it has not been demonstrated that they increase the amount of hydrochloric acid or of the digestive ferments. 124 PHARMACOPEIA AND PHYSICIAN. Gottlieb, in experimenting on rabbits with vola- tile oil of mustard and with pepper, found an in- creased pancreatic secretion, both solids and liquids, from irritation of the gastric mucous membrane. He admits the possibility of the absorption of a part of such volatile substances and a consequent direct stimulation of the secretory cells of the pan- creas, but he obtained a similar increase of pan- creatic secretion by reflex stimulation, using as irri- tants 0.5 per cent, acid and strong alkalies, which are not nearly so apt to be rapidly absorbed. Gott- lieb’s results with volatile oil of mustard have been criticized because he used as much as half a drop for a rabbit — a dose which might be termed mas- sive, considering the size or the weight of the ani- mal, but the rabbit’s gastrointestinal canal is prob- ably not so easily irritated as is that of man. In support of the claim that the pancreatic se- cretion is reflexly stimulated are the results of Bernstein and Heidenhain’s experiments on dogs. These observers found that pancreatic secretion begins so soon as food is taken, when reflex stimula- tion alone could cause it. All volatile oils have an antiferment action, and the aromatics, therefore, may lessen gastric fer- mentation. The slightly irritant effect, with the hyperemia, must be the main factors in their effects on diges- tion after that of reflex stimulation, for pancreatic secretion has been found to be much more mark- edly influenced by the dilation of blood vessels and a consequently free circulation than by changes of blood pressure : thus free secretion has been ob- STOMACHICS. 125 served after chloral, with dilated vessels and low blood pressure. In this connection it is to be remembered that nausea, pain in the stomach and other symptoms of functional disturbances of the gastrointestinal canal are often promptly relieved by external ap- plication of heat or even by a mustard footbath, which can only act reflexly. It is easy to understand why pure air and inter- esting surroundings play such an important role in appetite and digestion when we consider how completely those functions are under the control of the reflexes, mere change of location being much less important than the substitution of interesting for monotonous surroundings, and in advising change of scene with outdoor life these details can not be too carefully considered. Bitters, and more particularly the aromatic bit- ters, are indicated in loss of appetite when it is not due to grave gastric disturbances. When catarrh of the gastric mucous membrane complicates the condition, an astringent bitter, such as serpenta- ria, cimicifuga or cinchona, should be used. In the absence of catarrh, indigestion accompanied by in- sufficient gastric secretion, a simple bitter, such as gentian or calumba, may be used alone, but it is very much more often advisable to combine the simple bitters with aromatics. The individual taste of the patient should al- ways be considered in the choice of the aromatic. Men often like simple bitters, such as gentian or gentian and orange, a fact attested by the extraor- dinary popularity a few years ago of a certain bit- ters, which consisted practically of compound tine- 126 PHARMACOPEIA AND PHYSICIAN. ture of gentian. Women usually prefer mildly aro- matic and not very bitter substances, while chil- dren are generally averse to them altogether. When excess of acidity exists bitter substances will probably increase the trouble. Just as bitters and aromatics produce a greater effect in cases of functional disturbances, so iron is useful in ane- mia. though it has little influence in health, and it is often found advisable to combine iron with bit- ters, in which case the astringents are to be avoided because of the chemic reaction, whereby an inky mixture is formed, disagreeable alike to sight and taste — two great objections in this class of reme- dies. Many hitters which are not usually classed as astringents contain enough tannin or similarly act- ing substances to give inky mixtures with ferric salts ; such, for instance, are gentian and nux vomica. Calumba, therefore, is to be given the preference in all cases in which a bitter is to be combined with a soluble salt of iron. Detannated preparations of cinchona and even solutions of the cinchona alkaloids have little to recommend them in preference to calumba as a simple bitter. The following is an example of a simple bitter combined with iron : R. Tinct. calumbae Jiii 1001 Tinct. ferri chloridi . . m. Ixxv 5| Aquae q. s. ad Jvi 200 1 M. Sig. : A tablespoonful may be given half an hour before meals to men. while a teaspoonful will usually suffice for women. 1 7. While small doses of iron, well diluted, may be given with bitters before meals, if larger doses are given after eating they are borne better than they would be if given on an empty stomach. STOMACHICS. 127 The possible combinations of aromatic bitters are infinite, and, as previously stated, the indi- vidual taste is to be considered rather than slavish adherence to any one formula. Of the official aromatic bitters we may enumer- ate: Calamus. — TJ. S. — Sweet Flag. — The dried rhizome of Acorus Calamus was known to the an- cients and is still largely used in Europe, though not so popular in this country. Fluidextractum Calami. — U. S. — This is made with 75 per cent, alcohol. Average dose: 1 e.c. (15 minims). Aurantii Amari Cortex. — U. S. — Bitter Orange Peel. — The dried rind of the unripe fruit of Citrus vulgaris has long been used as an aro- matic bitter, but is chiefly used as an addition to other drugs, as in the compound tincture of gen- tian and the compound tincture of cinchona. Fluidextractum Aurantii Amari. — U. S. — This is made with 65 per cent, alcohol. Average dose: 1 c.c. (15 minims). Tincture Aurantii Amari. — U. S. — This rep- resents 20 per cent, of the crude drug and contains 60 parts of alcohol. Average dose: 4 c.c. (1 fluidram). ASTRINGENT BITTERS. Drugs that might properly be classed as astrin- gent bitters are numerous, and, therefore, we shall enumerate but a few of the more interesting or more popular. Cimicifuga. — U. S. — The dried rhizome and roots of Cimicifuga racemosa, a plant that is a na- 128 PHARMACOPEIA AND PHYSICIAN. tive of North America, have been used extensively in some sections of the United States. Fluidextractum Cimicifuga. — U. S. — This is made with strong alcohol. Average dose: 1 c.c. (15 minims). Tinctura Cimicifuga. — U. S. — This is made with alcohol. Average dose: 4 c.c. (1 fluidram). Serpentaria. — U. S. — The rhizome and roots of Aristolochia Serpentaria, popularly known as Virginia snakeroot, have been used in Europe for over 200 years. Fluidextractum Serpentaria. — U. S. — This is made with 80 per cent, alcohol. Average dose: 2 c.c. (30 minims). Tinctura Serpentaria. — U. S. — This repre- sents 20 per cent, of the crude drug and is made with a menstruum containing 65 parts of alcohol. Average dose: 4 c.c. (1 fluidram). Hydrastis.— U. S.- — -The rhizome and rootlets of Hydrastis canadensis, a perennial plant that is indigenous to Canada and the United States east of the Mississippi Eiver. Fluidextractum Hydrastis. — U. S. — This is made with a menstruum containing 60 parts of alcohol, with glycerin and water, and should con- tain not less than 2 per cent, of hydrastin. Average dose: 2 c.c. (30 minims). Tinctura Hydrastis. — U. S. — This represents 20 per cent, of the crude drug and is made with 65 per cent, alcohol. Average dose: 4 c.c. (1 fluidram). Cinchona. — U. S. — While undoubtedly better known and more extensively used as a bitter stoma- chic than any of the preceding, it is unnecessary STOMACHICS. 129 to recount the origin or the uses of this drug. It is official under two titles: Cinchona and Cinchona Eubra. Of the former we have : Fluidextractum Cinchona. — U. S. — This is made with 80 per cent, alcohol and contains 4 per cent, of the ether-soluble alkaloids of cinchona. Average dose: 1 c.c. (15 minims). Tinctura CiNCHONiE. — U. S. — This represents 20 per cent, of the crude drug and should contain 0.75 per cent, of cinchona alkaloids. Average dose: 4 c.c. (1 fluidram). The only official preparation of red cinchona is the old, and still popular, Huxham’s tincture of bark. Tinctura Cinchona Composita. — U. S. — This represents 10 per cent, of red cinchona, 8 per cent, of bitter orange peel and 2 per cent, of serpentaria. Average dose: 4 c.c. (1 fluidram). For an astringent bitter the fluid extract or the tincture of cinchona, cimicifuga or serpentaria may be combined somewhat as follows : R. Fl. ext. cinchona Tinct. gentian* comp., aa 3xii 50 1 M. Sig. : One teaspoonful to be given before meals. For women it will be well to increase the amount of aromatics, in which case the compound tincture of cardamom may be substituted for the compound tincture of gentian and the mixture even further diluted with aromatic elixir, if thought desirable, as follows: R. Fl. ext. cinchona 3v 20 1 Tinct. cardamomi comp. Elixir aromatici, aa 3x 40 1 M. Sig. : One teaspoonful of this mixture, with water, to be given before meals. 130 PHARMACOPEIA AND PHYSICIAN. Nux Vomica. — U. S. — The dried ripe seed of Strychnos Nux vomica, although not containing sufficient tannin to be classed as an astringent bit- ter, is frequently used as a bitter stomachic. The available preparations are : Fluidextractum Nucis Vomicae. — U. S. — This contains 1 per cent, of strychnin. Average dose: 0.05 c.c. (1 minim). Tinctura Nucis VoMiciE. — U. S. — This con- tains 2 per cent, of extract of nux vomica and is assayed to contain 0.1 per cent, of strychnin. Average dose: 0.6 c.c. (10 minims). 8 CARMINATIVES. The origin of this word is in doubt, some au- thorities maintaining that it comes from carmen, a charm, and the term is even now used somewhat loosely for those agents which produce a sense of warmth and well-being and which act as antispas- modics, or which expel gases from the gastrointes- tinal canal. When given with cathartics they lessen the griping pain of these drugs, and, being 8. A mixture of nux vomica and sodium bicarbonate offers a number of advantages as an efficient and comparatively harmless stomachic. It is made as follows : R. Tinet. nucis vom m. lxxv 51 Sodli bicarb gr. cl 10 1 Aqu® dest. q. s. ad 5v 150 1 Although technically this formula involves an incom- patibility, practically it is very satisfactory indeed. If the mixture is filtered and allowed to stand for 24 hours before being dispensed it will be found to have developed a very pleasant ethereal odor that adds materially to its effective- ness. The usual dose for adults is one tablespoonful before meals. For a patient with chronic constipation the addition of 1 or 2 c.c. (15 to 30 minims) of the fluidextract of cascara sagrada will be found to be highly satisfactory. One argu- ment In favor of this combination is that tt contains little alcohol — virtually none. STOMACHICS. 131 antiseptic, they inhibit the formation of gas by fermentation. According to the accepted definition a greater or less number of substances can be included in this particular class. The official carminatives afford a very wide range of choice^ as they include practi- cally all aromatic bitters, nearly all the aromatic volatile oils, besides such substances as ginger and capsicum, which contain pungent resinous constitu- ents, alcohol, ether, chloroform and many other agents which produce a sense of warmth when swal- lowed. Carminatives are among the most ancient of rem- edies and are indicated in pain in the stomach or bowels when due to simple indigestion or disten- tion by gas, but not when there is inflammation: in the latter case — for instance, in appendicitis or in peritonitis — carminatives are apt to augment the trouble. Many of these substances are well known as household remedies and, therefore, it will suffice to enumerate only the more important ones. Zingiber. — U. S. — Ginger has been used from time immemorial in eastern Asia; it was well known to the ancient Greeks, and is even now. perhaps, the most popular of all the carminatives. The most widely used of the official preparations is the tincture. Tinctura Zingiberis. — U. S. — This represents 20 per cent, of the crude drug exhausted with alco- hol. Average Dose: 2 c.c. (30 minims). Dluidexteactum Zingiberis. — IT. S. — This is an alcoholic extract. Average Dose: 1 c.c. (15 minims). 132 PHARMACOPEIA AND PHYSICIAN. Oleoresina Zingiberis. — U. S. — This is now prepared by means of acetone. Average Dose: 0.03 gm. (% grain). Half a teaspoonful, as noted above, of the tinc- ture may be given in a little hot water or with sugar. The oleoresin is much more active, and a drop of it may be thoroughly well mixed with powdered sugar and from one-eighth to one-fourth of the quantity given to a child, but not to an infant. It may also be added in half-drop doses or less to bulky cathartic pills or mixtures, but in either case it should be well diluted. THE OFFICIAL MINTS. Of the large number of aromatic drugs of the mint family, two have attained more than ordinary popularity as carminatives. The revisers of the Pharmacopeia have, indeed, been impartial in their description of these two substances and have treated them absolutely alike, so that from their status as official drugs it would be difficult to say whether peppermint or spearmint should be ac- corded the preference. It will be safe to assert, however, that peppermint is the more widely used. It is official as : Mentha Piperita. — U. S. — Peppermint. — The dry leaves and flowering tops. • Average Dose: 4 gm. (1 dram). This is some- times used in infusion. Oleum Menthh? Piperita. — U. S. — This is a volatile oil distilled from the fresh and partly dried leaves and flowering tops of peppermint. Spiritus Mentha Piperita. — U. S. — This is an alcoholic solution of 10 parts of oil of pepper- STOMACHICS. 133 mint filtered through 1 part of bruised peppermint, which imparts to it a distinct greenish color. Average dose: 2 c.c. (30 minims). Aqua Menth^e Piperita. — U. S. — This is a saturated aqueous solution of oil of peppermint. Average dose: 15 c.c. (4 fluidrams) . As above noted, spearmint, Mentha viridis , is official under closely corresponding headings and the doses are, of course, the same. The uses of these official mints are too numerous and too well known to require description in detail. They appear to be particularly useful in gastric fermentation, for which purpose they are usually given in connection with a mild alkali, like sodium bicarbonate, preferably in the well-known mixture of soda mint of the National Formulary or the widely used soda-mint tablets. 9 Accumulations of gas in the stomach which prove most distressing can often be promptly re- lieved by administration of 20 grains of sodium bicarbonate or potassium bicarbonate dissolved, preferably in hot water, to which from 10 to 20 drops of spirit of peppermint or spearmint may be added. 9. The Mistura Sod® et Menthse of the National Formu- lary consists of : Sodium bicarbonate grs. lxxv 5| Aromatic spirit of ammonia m. 1 II Spearmint water to make Jiii 100 1 Mix and filter. The average dose of this preparation is from 2 to 3 tea- spoonfuls. Soda mint tablets as furnished by manufacturers usually consist of 0.3 gm. (5 grains) of sodium bicarbonate with 0.002 (1/30 minim) of oil of peppermint. 134 PHARMACOPEIA AND PHYSICIAN. ASAFETIDA. Asafcetida. — U. S. — A gum resin obtained from the root of one or more species of Ferula. was held in high esteem by the ancient Greek physicians and has been popular with all classes of medical practitioners since that time. Average dose: 0.25 gm. (4 grains). As an addition to other carminatives, asafetida in substance was at one time very popular. At present it is but infrequently administered in any other form than suppositories. These are largely used after surgical operations to overcome the atony and partial paralysis that frequently accom- panies surgical interference in the abdomen. The only official preparations containing asafetida in substance are: Pilule Asafietida. — U. S. — Each pill con- tains 0.2 gm. (3 grains) of asafetida and 0.06 gm. (1 grain) of soap. Average dose : 2 pills. Tincturf Asafcetida. — U. S. — This repre- sents 20 per cent, of asafetida in alcohol. Average dose: 1 c.c. (15 minims). Emulsum Asafcetida. — IT. S. — This represents 4 per cent, of asafetida in water. Average dose: 15 c.c. (4 fluidrams). This preparation is also used extensively, as a clyster, to relieve accumulations of gas in the in- testines, after abdominal operations. It was at one time a very popular remedy for colic in infants, but the nauseous taste makes it very disagreeable and the greater number of infantile complaints, in which it might be indicated, are much more effec- tively treated with a laxative such as castor oil or STOMACHICS. 135 magnesia, and by the application of heat to the abdomen. The pernicious habit of using such preparations as Mrs. Winslow's Soothing Syrup, Chamberlain's Colic, Cholera and Diarrhea Remedy, Kopp’s Baby Friend 10 and others which have been exposed in The Journal, can not be too strongly condemned. If an opiate is thought to be necessary, it is much better to advise the nurse or mother to give five drops or more of paregoric, with warnings about the disadvantages and the dangers of its indiscrimi- nate use. CHLOROFORM AND ETHER. Chloroform. — TJ. S. — As a carminative, chloro- form probably deserves a much more extended use than it now has. Average dose: 0.3 c.c. (5 minims). This may be given either on sugar, in shaved ice, or in ice- cold water. Spiritus Chloroformi. — TJ. S. — This contains 6 per cent, of chloroform in alcohol. Average dose: 2 c.c. (30 minims). Emulsum Chloroformi. — TJ. S. — This con- tains 4 per cent, of chloroform with a small propor- tion of expressed oil of almonds, emulsified with tragacanth. Average dose: 8 c.c. (2 fluidrams). The spirit of chloroform, diluted with aromatic elixir, or the emulsion of chloroform given alone, promptly affords a sense of warmth in the stom- ach and will usually give relief in cases of colic and pain. JEther. — TJ. S. — Ether, sulphuric ether of the 10. See The Jocrxal A. M. A., vol. xliv, p. 666. 136 PHARMACOPEIA AND PHYSICIAN. early pharmacopeias has long been in nse as a car- minative. Average dose: 1 c.c. (15 minims). Spiritus TEtheris. — U. S. — This contains about 33 per cent, of ether. Average dose: 4 c.c. (1 fluidram). Spiritus aEtheris Composites. — TJ. S. — The well-known and widely used Hoffman’s anodyne contains in addition to ether about 2.5 per cent, of ethereal oil. Average dose: 4 c.c. (1 fluidram). Compound spirit of ether, in addition to its other uses, has long enjoyed a special reputation in hysteria due to gastric disturbances. It is disagree- able to the taste, however, and probably possesses no advantage over hot whisky and water, or spirit of nitrous ether. Alcoholic liquids in general are often useful, but their use and their numerous disadvantages can not be advantageously discussed in this connection. cloves and other aromatic substances. Caryophyllus. — TJ. S. — Cloves. — The dried flower buds of Eugenia aromatica. This remedy appears to have been known to the early Egyptians, but was not known to the later Greeks. In Europe this drug, probably introduced by the Arabians, has been known for centuries. Average dose: 0.25 gm. (4 grains). Oleum Caryophylli. — TJ. S.— This is a vola- tile oil distilled from cloves. Average dose: 0.05 c.c. (1 minim). The oil of cloves is much more frequently used for its anesthetic and caustic effect on exposed nerves in carious teeth than as a carminative, but STOMACHICS. 137 it may be used for the latter purpose, iu which case it is better to add it to spirit of peppermint or some other alcoholic carminative preparation, be- fore diluting with water. Oil of cinnamon resembles oil of cloves in its carminative effect, and the official tincture of cin- namon is also useful for the same purpose, but is more commonly employed as an adjuvant or flavor for other more active carminative agents, and in diarrhea. Mustard, pepper and nutmeg are not used med- icinally as carminatives, but are much employed as condiments to serve practically the same purpose. CHAPTER Y. ASTRINGENTS. Astringents are substances which produce a con- striction of all the solid tissues with which they are brought into intimate contact. All substances that are capable of forming precipitates of albu- min and gelatin, which are insoluble in the body fluids, are capable of acting as astringents. Sub- stances of this class have a peculiar action on mu- cous membranes, causing wrinkling of their sur- faces and diminution of secretion ; they precipitate not only proteids and gelatin, but also alkaloids and many glucosids. The action of astringents, irritants and caustics is largely a matter of degree, the caustics acting as astringents when sufficiently diluted, while all as- tringents produce at least a transient and slight irritation, and when applied in concentrated form to mucous membranes many of those classed as mere astringents are capable of causing consider- able irritation, which in the stomach may give rise to vomiting, and in the intestine to diarrhea. Some astringents are essentially mild in their action, while others, being nearly insoluble, can not be brought into intimate contact with the tissues in concentrated form; these can not produce more than a very mild and fleeting irritation, or stimu- lation, which is followed by lessened permeability of the capillary walls and diminished congestion. Bv their irritant action, drugs of this partic- ASTRINGENTS. 139 ular class may increase a severe acute inflamma- tion without being able to produce their typical as- tringent effect, hence they are not nearly so useful in such conditions as in chronic inflammations. The vegetable astringents owe their action mainly to the presence of tannins, substances belonging to an ill-defined group, possessing an astringent ac- tion as their best defined property. Other or- ganic acids play only a minor role as astringents. The tannins give blue-black or greenish-black re- actions with ferric salts; they precipitate proteids (leather being the product formed with connective tissue), alkaloids, metals and some other sub- stances; they yield pyrocatechin or pyrogallol on destructive distillation. Their therapeutic actions are independent of their chemical peculiarities, and they are severally indicated rather with reference to the presence or absence of extractive matter. The combination of tannin with peptone is sol- uble in the gastric juice, and this and the insoluble albumin tannates are decomposed in the alkaline juice of the intestine, the tannin forming alkaline tannates which possess little or no astringent ac- tion. If the free tannins reach the intestine after the administration of extracts of the crude drugs, they act on the mucous membrane, lessening intes- tinal secretion; this greatly modifies the bacterial development, and, therefore, the general intestinal conditions. Some of the metallic albuminates are soluble in an excess of proteid, and when in such a case the liberated acid is corrosive, there is a pen- etrating corrosive action such as that of zinc or mercuric chlorid. With an insoluble precipitate, sucb as lead albuminate, which forms an imper- vious coating, and a mildly astringent acid, like 140 PHARMACOPEIA AX D PHYSICIAN. acetic, there is a typical astringent and non-irri- tant effect. The same astringent substance may be used in a variety of conditions, and a number of different astringents are applicable to a given condition. A better acquaintance with the different tannins may lead to the selection of certain ones for particular cases, but at the present time we are guided more by the physical condition in which a given one is available; thus the official tannic acid is readily dissolved in the stomach, where it combines with the proteid of the content, or with the mucous mem- brane, whereas the tannin of gambir (gambir re- places the catechu of the Pharmacopeia of 1890) is protected by the presence of gum and extractives, and so passes into the intestine, there to exert its astringent effect. We can not attempt anything like a complete enumeration of the various uses of the astringents, but must content ourselves with summarizing briefly the principal indications of astringents and some of the chief characteristics of the more common remedies of this type. USES OF ASTRINGENTS. Astringents are used internally in the treatment of diarrhea and dysentery, in congestion of the mu- cous membrane of the stomach and intestines, and for hemorrhage in the alimentary canal and other directly accessible regions. The use of astringents — either organic or inorganic — for their effects on parts which can only be reached by way of the blood vessels is wholly irrational, and when benefit follows it is not due to the astringent action, since by their very nature astringents can not exist free in the blood in sufficient concentration to exert an ASTRINGENTS. 141 astringent action. Traces of tannin are not as- tringent any more than the}" are irritant, and as- tringents act only when brought into intimate con- tact with the tissue in sufficient concentration. The metals are poisonous when absorbed, and, as a rule, vegetable astringents are to be preferred for internal administration, particularly when they must be used for a considerable period. Pure tan- nin. or tannic acid, as it is designated in the Pharmacopeia, may be used locally whenever a purely astringent action is indicated; for example, when secretion is excessive, and when it is desired to harden the skin in order to prevent excessive sweating. The treatment of accessible, inflamed mucous membranes with antiseptic solutions, and more parficularl}" with solutions of hydrogen dioxid, has greatly lessened the use of astringents, and the cleansing of an infected surface should be a rou- tine procedure even when an astringent is to be applied subsequently. Dry tannin insufflated against an elongated palate often affords instan- taneous relief. Tannin in the pure state is rarely used inter- nally because of its irritant action on the stomach, one of the preparations of astringent drugs being preferred in such cases. The dry powder acts as a styptic when applied to bleeding surfaces, but it must be borne in mind that tannic acid and all other astringents when given by mouth exert their astringent action only on the alimentary canal. The various proprietary remedies, composed of tannin and albumin, gelatin or albuminoids, have not been shown to possess any decided therapeutic advantages over the official astringents, and sev- 142 PHARMACOPEIA AND PHYSICIAN. eral of the proprietary compounds, owing to their variable composition, must necessarily be uncertain in their actions. Tannic acid in simple solution combines with the albuminous contents of the stomach, and with the mucous membrane itself if the stomach be empty and the tannin in concentrated solution; it may then give rise to vomiting and even to diarrhea. This irritant action of the astringents leads to the use of several of them — alum, and zinc and copper sulphate — as emetics. Tannin, being a precipitant of alkaloids, is use- ful as an antidote to those poisons when they are in the stomach— not when they have been given hypodermically, except possibly in the case of mor- phin, which is excreted into the stomach. The tan- nates thus formed are slowly broken up, and the stomach must be evacuated by emetics, or. prefer- ably, by the stomach pump, as promptly as pos- sible, tannin being added to the water which is used to wash the stomach after evacuation. Tea and coffee contain tannin, and, since they are al- most universally available in emergencies, their use is very common. Torald Sollmann 1 made some experiments to determine the efficiency of infu- sions of tea and coffee as precipitants for various alkaloids and metals, and found the infusion of tea much the more active, but neither of them very reliable for the commonly used alkaloids, while the only metals for which tea (infusion) would be useful are mercury, lead and silver. As a single dose of lead never gives rise to poisoning, and as poisoning with silver salts is extremely 1. Journal of Medical Research, vol. vli, No. 1, p. 43. ASTRINGENTS. 143 rare, we must conclude that poisoning with mer- curic salts is practically the only instance likely to be encountered in which tea would prove to be an effective precipitant. The use of tea and coffee as stimulants in poisoning depends mainly on the caffein, and, of course, these remarks as to their limitations do not apply to the stimulant use of them. VEGETABLE ASTRINGENTS. Acidum Tannicum. — U. S. — This is a light yellowish amorphous powder of a characteristic odor and a strongly astringent taste; it is very soluble in water, alcohol or glycerin. Average dose: 0.5 gm. (8 grains). Gltceritum Acidi Tannici. — U. S. — A 20 per cent, solution of tannic acid in glycerin. Average dose: 2 c.c. (30 minims). Trochisci Acidi Tannici. — U. S. — Each troche contains 0.06 gm. (1 grain) of tannic acid with sugar and tragacanth, flavored with orange- flower water. These troches are used almost exclusively in af- fections of the mouth and throat. Gambir (catechu), kino, krameria and many other vegetable drugs contain large amounts of their peculiar tannins, together with mucilaginous and other extractive matter which tends to pre- vent the tannin from forming compounds in the stomach and thus preclude its action on the mu- cous membrane before it comes into the intestine, hence the preparations of these substances are more useful in the treatment of diarrhea than are pure tannin and its preparations. Gambir. — TJ. S. — Gambir was introduced into 144 PHARMACOPEIA AND PHYSICIAN. the present Pharmacopeia to replace catechu of the earlier editions. It is an extract prepared from the leaves and twigs of Ourouparia Gambir and oc- curs in irregular masses, varying in color from reddish brown to a pale brownish gray. It is in- odorous, hut has a slightly bitter, .very astringent taste, with a sweetish after-taste. Average dose: 1 gm. (15 grains). Tinctura Gambir Composita. — IJ. S. — This represents 5 per cent., of gambir and 2.5 per cent, of Saigon cinnamon in diluted alcohol. Average dose: 4 c.c. (1 fluidrachm). Trochisci Gambir. — U. S. — Each troche con- tains 0.06 gm. (1 grain) of gambir with sugar and tragacanth, flavored with orange-flower water. These troches are well adapted for use in sore throat, after the throat has been sprayed with a solution of hydrogen dioxid, instead of the as- tringent gargles which were formerly so much in vogue. Kino. — U. S. — The inspissated juice of Ptero- carpus marsupium was introduced into medicine by Dr. John Fothergill about 1757. Like Gambir, it may be given as a powder, preferably combined with opium and aromatics, as in the “Compound Kino Powder” K. F. Average dose (of kino) : 0.5 gm. (8 grains). Tinctura Kino. — U. S. — The strength of this preparation has been reduced to 5 per cent, to obviate its tendency to gelatinize. Average dose: 4 c.c. (1 fluidrachm). The following prescription, though somewhat complex, is a slightly modified form of one used in certain hospitals with satisfactory results ; al- though the chalk is alkaline, it does not apprecia- ASTRINGENTS. 145 bly lessen the astringency of the mixture, as do the carbonates of the alkalies which exist in the in- testine. The compound tincture of gambir, or the tincture of krameria, may be used instead of the tincture of kino. R. Cretae preparatae 3i 4 Tincturoe kino 3iv 15 Tincturse opii m. v 3 Spiritus chloroformi m. lxxv 5 Aquae menthae piperitae 3x 40 Syrupi aurantii q. s §iii 100 For children of from '3 to 10 years of age, from one-half to one teaspoonful of this mixture may be given every two or three hours ; for adults the dose is one tablespoonful. Another combination of chalk which has at- tained very great popularity in the treatment of diarrhea is the : Mtstitra Cretai. — IJ. S. — Chalk Mixture has the following composition : R. Cretae preparatae gr. xc 6 Pulveris acaciae 3i 4 Pulveris sacchari gr. cl 10 Aquae cinnamomi 3x 40 Aquae q. s. ad 3iii 100 Average dose: 15 c.c. (4 fluidrachms). The mixture is so well known that it is men- tioned merely as a reminder of one of our best and simplest remedies for diarrhea. It is peculiarly adapted for combating the diarrhea of children. Severe cases may require the addition of a few drops of the deodorized tincture of opium to each adult dose, or a corresponding addition of pare- goric (the camphorated tincture of opium) for children. The vegetable drugs that contain tannin are so ' numerous, and their general therapeutic actions 146 PHARMACOPEIA AND PHYSICIAN. are so similar, that we shall merely enumerate the following well-known vegetable astringents and the available, official, preparations : Eubus (blackberry-root bark) — Fluidextract and Syrup. Eed Eose — Fluidextract and Syrup. Geranium — Fluidextract. Hematoxylon — Extract. Ehus Glabra — Fluidextract. Gallic acid is sometimes recommended as an astringent, but it possesses no such action except that of any very weak acid, and it is absolutely useless for hemorrhage in the lungs, kidneys and other regions reached only by the circulation. Though opium does not contain tannin, it would be a distinct omission if we failed to mention some of its indications in this place, since this work is intended primarily to call attention to the pos- sible therapeutic uses of the official substances, and since the arrangement into groups, such as as- tringents, is merely for convenience. Small doses of any of the opium preparations afford one of the surest means of relief in diarrhea. They are com- monly combined with astringents, inorganic as well as organic, with excellent results, despite the chemical incompatibility existing between the alka- loids and the various tannins or metallic salts. The preparations of opium will be mentioned in the later chapters, and we now merely wish to call attention to methods of combining these agents. R. Tinctura gambir composita 3i 301 Tinctura opii deodoratae m. x 5 Bismuthi subnitratis 3iiss 10 1 Aqua camphora q. s Siii 100 1 Sig. : One teaspoonful hourly for three or four hours, then every two or three hours. ASTRINGENTS. 147 Any one of the insoluble bismuth salts may be used, and tincture of kino or krameria substituted for the compound tincture of gambir. Similarly, an appropriate amount of the camphorated tinc- ture of opium may be substituted for the deodor- ized tincture. When it is desired to give the same active ingredients in the form of a dry powder, the following may be used : R. Opii pulveris gr. r |3 Bismuthi subnitratis gr. cl 10) M. Ft. pulvis et div. in chart, x. Sig. : One powder to be given every two, three or four hours, according to the needs of the patient. Here, again, the combination may be varied almost endlessly by using one of the other in- soluble bismuth salts, the deodorized opium, or by adding a small proportion of one of the veget- able astringents like kino or gambir. The pill of lead and opium is well adapted for securing a very slowly soluble form for adminis- tering these drugs. The pill is useful in diarrhea, but must not be long continued, lest it give rise to lead poisoning. R. Plumbi acetatis gr. ii |1 Opii pulveris gr. i j 05 To be made into one pill. Sig.: One pill to be given three or four times a day. Inflammation of the stomach and intestine and gastric ulcer may be treated by an insoluble astringent powder which not only relieves conges- tion by its astringent property, but also forms an insoluble protective covering, preventing the con- tact of irritating particles of food and the gastric and intestinal secretions, besides lessening the amount of these secretions. 148 PHARMACOPEIA AX D PHYSICIAN. METALLIC ASTRINGENTS. The insoluble salts of bismuth are admirably adapted for the protection of the intestinal mu- cosa from irritants of various kinds. While as much as thirty times the average single dose of bismuth salts has been given in the course of a day, by the mouth, without any distinct evidence of un- toward results, absorption and poisoning have fol- lowed the external use of bismuth salts as a dusting powder when used over a large surface. Owing to the extremly poisonous nature of bis- muth when absorbed, the soluble salts seem to us to be entirely superflous, particularly as their solu- bility precludes the very object for which bismuth compounds are chiefly used — that is, for the me- chanical coating of the surface Avith a protective layer of insoluble powder. It must be admitted, of course, that even the soluble salts of bismuth are astringent, but we have many safer astringents which are harmless that might well be used in their stead. The activity of the nostrum-makers has resulted in placing on the market a number of preparations that are intended to combine the antiseptic proper- ties of the benzene derivatives with the astringent properties of bismuth, but until we know more of the possibilities and the limitations of internal an- tiseptics it is preferable to use the simple astrin- gents and to use our antiseptics separately. Bismuth subnitrate, or subcarbonate, when trit- urated with water, should form a creamy mixture, and the physician should not permit the use of that which readily separates as a heavy powder, leaving a nearly clear stratum of liquid above it. The coa-- ASTRINGENTS. 149 ering power of bismuth is in direct proportion to the creaminess of the mixture. 2 Bismuthi Subnitras. — U. S. — An insoluble white powder, without odor or taste. Bismuthi Subcarbon'as. — U. S. — Closely re- sembles the subnitrate. Average dose (of either salt) : 0.5 gm. (8 grains ) . Bismuthi Subsalicylas. — IT. S. — This prepar- ation closely resembles the subnitrate in physical properties and is intended to combine the anti- septic properties of the salicylic acid with the as- tringency of bismuth salts. Average dose: 0.25 gm. (4 grains). Bismuthi Subgallas. — U. S. — This preparation was at one time widely advertised and is even now occasionally prescribed by its proprietary name, dermatol. It occurs as a bright yellowish, insol- uble, odorless and tasteless powder, which is mostly used externally as a substitute for iodoform. 2. A typical prescription for gastric irritation, or ulcer is as follows : Bismuthi subnitratis grs. cl 10 1 Mucilaginis acacia; 3xii 50] Aquae cinnamomi q. s. ad giii 100 1 M. Sig. ; Shake well and take one or two teaspoonfuls three or four times a day. In cases in which marked irritability persists, the addi- tion of 0.01 gm. (1/6 grain) of cocain hydrochlorid to each dose, as a local anesthetic, may be advantageous, but we do not advise' it as a routine procedure. For diarrhea one or two drops of the deodorized tincture of opium may be in- cluded for each dose, or, if preferred, tincture of opium. For this purpose, it is usually preferable to give one dose every hour for three or four doses, then every two to four hours as needed. Bismuth subcarbonate may be used instead of the subnitrate and tincture of kino, tincture of krameria or the compound tincture of gambir (catechu) may be added in the treatment of diarrhea. 150 PHARMACOPEIA AND PHYSICIAN. Average dose: 0.25 gm. (4 grains). OFFICIAL LEAD SALTS. Lead is of interest chiefly because of the chronic lead poisoning so often encountered. The principal internal use of lead is in the form of the pill of the acetate, usually combined with opium, in the treatment of diarrhea. It has also been recommended for dysentery, but is not nearly so useful in that disease. This preparation should not 'be given for any considerable length of time, lest it give rise to chronic lead poisoning. The solution of lead subacetate is unfit for internal administration, but is of value in painful swell- ings and local inflammations and burns. The well-known mixture of laudanum and lead water has long been popular as an external application, but any mucilaginous liquid could probably be used in place of the tincture of opium without detriment, since the astringency of the lead is the main factor, the local application of the opium alkaloids being entirely superfluous because they are not absorbed from the unbroken skin. The local use of lead water itself is so thoroughly well established that it scarcely requires further com- ment. 3 Plumbi Acetatis. — U. S.— Acetate of Lead, or 3. The following mixture will probably answer the pur- poses for which laudanum and lead water are commonly used : R. Liq. plumbi subacet min. lxxv 5 Mucil. acac min. xlv 3 Aqua, q. s. ad f. giii 100 The solution of lead subacetate is diluted with 55 c.c. (16 fluid drams) of water and the mucilage with 27 c.c. (8 fluid drams) the two are then mixed. Fifteen c.c. (4 fluid drams) of alcohol may be added to the water, but the amount of alcohol present in the mixture of laudanum and lead water is too small to be of any benefit. ASTRINGENTS. 151 sugar of lead, is said to have been known to G-eber. It was described by Raymund Lully in the thir- teenth century, but was not used in medicine until introduced by Goulard a little more than a century ago. It occurs in crystals or as a heavy white pow- der, having an acetous odor and a sweetish, astrin- gent, afterward metallic taste. Average dose: 0.05 gm. (1 grain). Liquor Plumbi Subacetatis. — U. S. — An aqueous solution containing not less than 25 per cent, of lead of subacetate. Liquor Plumbi Subacetatis Dilutus. — U. S. — This contains about 1 per cent, of lead subacetate and is made by mixing 4 parts of the solution of lead subacetate with 96 parts of distilled water. THE LOCAL TREATMENT OF MUCOUS MEMBRANES. The local treatment of inflammation of the mu- cous membranes in the mouth, nose, throat, vagina and urethra, after thorough cleansing, preferably with a solution of hydrogen dioxid, may require mild astringents of either organic or inorganic sub- stances, though, as previously stated, the use of the solution of hydrogen dioxid has greatly lessened this necessity. Alum has long enjoyed a particular reputation in the treatment of stomatitis, and has also been used as a gargle, but it is injurious to the teeth, and the necessary solution, made of 1 part of alum in 20 parts of water, is preferably applied directly to the affected parts by means of a camel’s- hair pencil or a swab made of absorbent cotton After gargling, the mouth should be rinsed with water. Alum is not given internally so often as it was formerly; it is irritating and possesses no ad- vantages over other astringents. Because of this 152 PHARMACOPEIA AM) PHYSICIAN. irritant action it is emetic, and, while not very dependable, may serve in an emergency if no surer emetic is at hand. Small ulcerations of the throat, after having been cleansed with an antiseptic so- lution, may be touched with a mixture of 1 part of ferric subsulphate and 2 parts of glycerin, using a camel’sfhair pencil or a cotton swab. A very large number of astringent gargles are in common use, but the following is a good represen- tative of the class : R. Tincturae ferri chloridi . . . . . . .m. cl 10 Potassii chloratis 3iii 12 Aquae q. s f. Bvi 200 Those who object to the use of ferric chlorid may find the following preferable : It. Glyceriti acidi tannici f. 3v 201 Aquae q. s f. §vi 200 j Alumen. — U. S. — Alum should contain not less than 99.5 per cent, of pure aluminum and potas- sium sulphate. It occurs as colorless crystals or as a white powder; it is odorless, but has a sweet- ish and strongly astringent taste. Alum is soluble in 9 parts of water, but is insoluble in alcohol. Average dose: 0.5 gm. (8 grains). Alumen Exsiccatum. — IT. S. — Popularly known as dried alum, must contain not less than 99 per cent, of anhydrous aluminum and potas- sium sulphate. It is used for the same purposes as alum, and in addition is somewhat caustic when dusted, as a dry powder, on exuberant growths. THE USE OF ZINC SALTS. Zinc sulphate and zinc phenolsulphonate may he considered together; they have a variety of appli- cations, and it is only necessary to suggest the ASTRINGENTS. 153 strength of the solutions that are to be used for various purposes. For the eye they are generally used in the strength of from one-fourth to one-half of 1 per cent, in a solution of boric acid, to which camphor water may be added. For the urethra strong solutions should not be used, one-half of 1 per cent, in water being suf- ficient. The popular combination of zinc sulphate and lead acetate, resulting in the insoluble lead sulphate and the very astringent zinc acetate, may possess some advantages over the more simple so- lution, but they are not very apparent. Vaginal douches may be somewhat stronger and are frequently prescribed of from 1 to 2 per cent, strength. As noted before, all the astringents may act as emetics if they are sufficiently irritant to the mu- cous membrane of the stomach and are not caustic. Zinc sulphate, however, deserves the preference among the astringents used as emetics. For this purpose it is usually given in doses of 1 or 2 gm. (15 to 30 grains dissolved in a teacupful of warm water) . The official salts of zinc that are of interest as astringents are : Zinci Sulphas. — TJ. S. — Colorless crystals, without odor, having an astringent metallic taste. Zinc sulphate is soluble in less than 1 part of water, but is insoluble in alcohol. Average dose: Emetic, 1 gm. (15 grains). Zinci Phenolsulphonate. — IJ. S. — The zinc sulphocarbolate of previous editions of the Phar- macopeia has been referred to under antiseptics. Average dose: 0.12 gm. (2 grains). 154 PHARMACOPEIA AND PHYSICIAN. Zinci Acetas. — U. S. — This constitutes a widely used and deservedly popular astringent. Average dose: 0.12 gm. (2 grains). Zinci Oxidum. — U. S. — A white or yellowish- white powder, insoluble in either water or alcohol, it is largely used as a local application in dusting powders and in ointments, but is seldom given in- ternally. Average dose: 0.25 gm. (4 grains). COPPER AND IRON SALTS. Cijpri Sulphas. — U. S. — Blue stone or blue vitriol was known to the Greeks as chalkanthos. Dioscorides described it as being a valuable astrin- gent and, in large doses, emetic. It occurs as deep blue crystals that are devoid of odor, but have a nauseous, metallic taste. It is soluble in about 3 parts of water. Average dose as an astringent: 0.01 gm. (10 mg. or 1/5 grain); -as an emetic, 0.25 gm. (4 grains) . Of the numerous preparations of iron that have astringent properties we will mention but one, the chlorid, as representative of the whole class. This is official in several forms : Ferri Chloridum. — U. S. — This occurs in orange-yellow crystalline pieces, nearly odorless, but having a strongly styptic taste. Average dose: 0.05 gm. (1 grain). Liquor Ferri Chloridi. — U. S. — An aqueous solution of ferric chlorid, containing about 29 per cent, of the anhydrous salt. Average dose: 0.1 c.c. (1% minims). This preparation is but little used, except for preparing Tinctura Ferri Chloride — U. S. — This is ASTRINGENTS. 155 made by adding 35 parts of solution of ferric chlorid to enough alcohol to make 100 c.c. The official tincture is directed to be prepared at least three months before being used. Average dose: 0.5 c.c. (8 minims). This preparation is injurious to the teeth; therefore it should be directed to be taken through a tube and the mouth rinsed with water or a very mild solution of an alkali, like limewater. USE OF SILVER NITRATE. Silver nitrate in the form of sticks, lunar caus- tic, is mainly used as a caustic for touching warts of various kinds and for non-granulating wounds. A solution of silver nitrate is sometimes used as an application to the conjunctiva, followed at once by a solution of sodium chlorid, whereby a mo- mentary action of the silver nitrate is obtained, the nitrate being instantly converted into the chlorid when the solution of sodium chlorid is applied. Silver in combination with different proteids has been introduced under a variety of trade- marked or proprietary names and recommended as a non-irritant antiseptic, mainly for the treat- ment of gonorrhea. Crede some years ago intro- duced a soluble form of metallic silver, for which certain manufacturers make the fabulous claim that it is an efficient disinfectant of blood and tis- sue. So long as septic diseases resist all treatment, it seems strange that reputable manufacturers will make such obvious misstatements. The only official preparation of silver that is of direct interest in connection with astringents is Argenti Nitras. — TJ. S. — This salt is supposed to have been known to Geber, but was introduced 156 PHARMACOPEIA AND PHYSICIAN. into medicine by Angelus Sala during the seven- teenth century. It is very soluble in water and oc- curs as colorless, transparent, tabular crystals, that darken on exposure to light in the presence of or- ganic matter. It is odorless, but has a bitter, caus- tic and strongly metallic taste. Average dose: 0.01 gm. (10 gm., or 1/5 grain). The internal use of silver nitrate as an astrin- gent is necessarily empirical, as the compound that is formed when silver nitrate is brought into contact with organic matter must be complex and problematic. A favorite pill of the late Dr. William Pepper for chronic gastritis was the fol- lowing. It is given without comment : II . Argenti nitratis Extracti hyoseyami Mannse, aa gr. 1/3 [02 To make one pill. This was directed to be given three or four times a day, and the composition was occasionally varied by substituting powdered opium for the ex- tract of hyoscyamus. VASOCONSTRICTORS. In addition to the astringent drugs depending on tannin or the metallic salts, certain alkaloids possess a markedly astringent, or, more properly, vasoconstrictor effect when applied to mucous membranes. Of these, the most useful are hydr'as- tinin, a derivative of hydrastin, from which it is obtained by oxidation, and the alkaloid of the suprarenal gland. Here we are compelled to admit that this latter alkaloid, which is now being mar- keted at the modest price of some $800 per ounce, despite Abel’s simple and inexpensive method of preparation, is superior to the official desiccated ASTRTXGEXTS. 157 suprarenal gland. The application of a 1 to 1,000 solution of hydrastinin or a 1 to 5,000 solution of the suprarenal alkaloid, in 0.9 per cent, solution of sodium chlorid, to an inflamed conjunctiva or inflamed nasal mucous membrane often affords prompt relief. In view of the very great difference in cost without a corresponding difference in ef- fect, the physician can well afford to use hydras- tinin in preference to the more expensive alkaloid in such conditions. The desiccated suprarenal gland may be mace- rated in water and the fluid filtered and used, but any of the preparations of the alkaloid which appear under a variety of trade names will usually be preferred. Slight hemorrhages are also stopped by either of these means. When the flow of blood is copious and hot water is ineffective, styptics are useful; they are not alone astringent, but also cause a sudden coagula- tion of the blood, and this plugs up the orifice. Large clots must be removed, as they prevent the immediate contact of the astringent or styptic and may conceal a hemorrhage occurring in cavities — the uterus, ' for instance — in which case the clot may fill the upper part of the vagina. It is necessary to bear in mind the difference be- tween the action of vasoconstrictors, like the alka- loid of the suprarenal gland, and the action of styptics, like tannin or the ferric salts. With the former the action is transitory and the hemorrhage may recur as soon as the action of the drug has worn away, while styptics, when effective, form a plug in the normal distended blood vessel. An- other point to be remembered, in this connection, is the fact that the absorption of a vasoconstrictor, 158 PHARMACOPEIA AX D PHYSICIAN. following its continued or too liberal use, will cause a general rise of blood pressure and thus actually increase the flow of blood at the bleeding points. Glandule Suprarenales Sicc^:. — IT. S. — Desiccated Suprarenal Glands are directed to be ob- tained from the sheep or os, freed from fat, cleaned, dried and powdered. One part of desic- cated suprarenal gland represents approximately 6 parts of fresh glands free from fat. Average dose : 0.25 gm. (4 grains) . The alkaloid contained in the suprarenal glands has been variously designated as epinephrin by Abel, suprarenin by Fiirth and adrenalin by Taka- mine. The trade names that are now applied to the solutions of the same substance are legion, and it seems ver} r unfortunate indeed that the commit- tee on revision of the Pharmacopeia did not recog- nize the alkaloidal substance in an official way and give it an official title. The only effect to be ex- pected from the internal administration of the gland or its alkaloid is the local constriction that is noticed when it is applied to the mucous mem- brane. The solution of the alkaloid is without ef- fect on blood pressure when given by the stomach and when injected just beneath the skin it pro- duces practically no effect, except a local vasocon- striction. CHAPTER VI. IRRITANTS, EMOLLIENTS AND DEMUL- CENTS. There are so many substances which have been used as irritants under varying conditions that we can not attempt to do more than mention the more useful of the agents frequently employed for this purpose, together with some of the conditions in which clinical experience has shown them to be most beneficial. While the employment of counter-irritants is almost wholly empirical, the regions of the skin which Brunton has indicated for their use when it is desired to influence the internal organs corre- spond well with those which Head has shown to exhibit tenderness of the skin in connection with diseases of the same organs. Brunton directs the irritant to be placed over the larynx, ovaries or sciatic nerve for affections of those parts, over the ensiform cartilage for gastric disturbance, above and below the knee in rheuma- tism, over the ball of the great toe (dorsal surface) in gout, behind the ear in facial neuralgia, at the base of the brain and back of the neck for cerebral affections, and along the dorsal region of the back to affect the uterus. The mildest of irritants is water or saline solu- tion used as a bath. The shock of the cold water applied to the skin and the slight irritation of the subsequent friction, preferably with a coarse towel, are followed by a reaction attended with a consid- ] 60 PHARMACOPEIA AND PHYSICIAN. erable and lasting stimulation. Very cold water may produce too great a shock in persons who are not robust, and the result will be depression, but there can be little doubt that baths are extremely beneficial when the temperature is so regulated that a healthy glow and a feeling of well-being succeed. It seems that the question of the useful- ness or the harm of cold baths, about which there has been so much contention, resolves itself into a question of individual experience. If a feeling of exhilaration, but no subsequent depression, fol- lows the bath it is not harmful ; if no such exhila- ration occurs, but a distinct depression is observed, there can be but little doubt that the bath is doing harm. In such cases a slight increase in the tem- perature of the water, with a shorter time and more rubbing, may secure the benefits sought. The same person may require different conditions of temperature at different times, corresponding to variations in the general health. A mixture of salts is sometimes added to the bath to increase the slight irritant action. Even milder than the friction, which forms so essential a part of the bath, is the irritant action of the astringents, which have been discussed in Chapter V, but these are followed by lessened irri- tation, hence they are not considered among the irritants. RUBEFACIENTS. Rubefaction is the result of a slight irritation of the skin. There is a slight increase in the exudate from the capillaries, and if the irritation be not long continued this exudate is Teabsorbed and the part speedily returns to the normal condition. R U BE FA Cl EX TS. 161 While all irritants, mild and caustic, cause rube- faction, we shall first consider only those 'which are used for that stage alone, and take up the vesi- cants, pustulants and caustics later. ALCOHOL. Alcohol alone, diluted with water or in the form of hamamelis water, alcoholic tinctures, spirits or liniments, is used more frequently, perhaps, than any other mild irritant, with the possible exception of the bath. Applications containing alcohol are useful in painful swellings, bruises and a great variety Of minor complaints commonly treated in the house- hold without calling on the physician. While it is probably quite unnecessary, at this late date, to call particular attention to the fact that there is a distinct and a very great difference between the official, or ethyl, alcohol and the various forms of wood, or methyl, alcohol, never- theless the insidiously poisonous properties of the latter substance do not appear to be well appre- ciated by the general public. The number of cases of blindness and of death that have been reported by Buller and Wood 1 amply demonstrate that even the external use of any form of wood alcohol is not entirely free from danger and that its use in any form of medicinal preparation should not be countenanced or tolerated. Among the numerous preparations of the United States Pharmacopeia that have been used as topical applications, largely because of the rube- 1. The Journal A. M. A., Oct. 1, 8, 15, 22 and 29, 1904. 162 PHARMACOPEIA AND PHYSICIAN. facient properties of the alcohol that they contain, we may enumerate : Aqua Hamamelidis. — U. S.- — This preparation, more popularly known as extract of witchhazel, or distilled extract of witchhazel, is now, for the first time, included in the Pharmacopeia. While the preparation itself has been known for many years, and has been used extensively as a household rem- edy, it has never met with much favor on the part of the medical profession. The official prepara- tion is directed to contain 15 per cent, of alcohol and should be free from methyl alcohol or any of its derivatives. Tincture Arnica. — U. S.— Tincture of arnica represents 20 parts of the dried and powdered flower heads of Arnica montana in diluted alcohol. This preparation was at one time very popular with medical practitioners as a topical application in so-called “sprains” and in bruises, but is now seldom employed. The same is true of : Tincture Calendula. — U. S. — This prepara- tion represents 20 per cent, of the dried and powdered florets of Calendula officinalis, the well- known marigold of our gardens. Probably the most objectionable feature in con- nection with the use of any of the official tinctures as topical applications is their tendency to stain. This objection is largely overcome by the use of the simple diluted alcohol, one of the numerous unofficial toilet waters or colognes, or by the use of one or the other of the official spirits. In addition to Spiritus Frumenti. — U. S. — Whisky, and Spiritus Yini Gallici. — U. S. — Brandy, the most frequently used of this class of preparations is : RUBEFACIENTS. 163 Spiritus Camphors. — U. S. — This is an alco- holic solution containing 10 per cent, of camphor. Spiritus Gaultherl®. — U. S. — This contains 5 per cent, of oil of gaultheria in alcohol. The most widely used, as well as the most pop- ular, of the mildly rubefacient liniments of the Pharmacopeia is : Linimentum Saponis. — U. S'. — Soap Liniment is variously known as liquid opodeldoc, camphor- ated soap liniment and camphorated tincture of soap. It contains 6 parts of soap, 4.5 parts of cam- phor, 1 part of oil of rosemary and 72 parts of alcohol with sufficient water to make 100 parts. This preparation has long been popular as a topical application and is not infrequently used as a ve- hicle for other more active rubefacients, sedatives and anodynes. A somewdiat typical compound liniment is the Liniment Chloroformi. — U. S. — This is a simple mixture of 30 parts of chloroform with 70 parts of soap liniment, and constitutes a very good illustration of the possible uses of soap liniment as a solvent or vehicle. CHLOROFORM. Chloroform is one of the more active rube- facients and the action quickly passes this stage if its use be continued. Chloroform readily dissolves fat, and, being very volatile, it penetrates quickly and causes considerable redness and pain. A few drops of chloroform placed on a little absorbent cotton and applied over a painful joint, such as a bunion, in such a way that evaporation of the chloroform is prevented, causes a good deal of pain but often affords speedy relief. It should not be 164 PHARMACOPEIA AND PHYSICIAN. applied in this way for longer than ten or fifteen minutes. Chloroform may be used as a counter- irritant by putting a few drops on cotton in a wide-mouthed bottle; the mouth of the bottle is then applied to the area to be treated, for a few minutes at a time. Chloroform liniment, noted above, is much less painful, or not at all so in most cases, and is much slower in producing its effects. Chloroform lini- ment is usually directed to be applied to the af- fected part by being thoroughly rubbed in, thus securing the additional rubefacient action of fric- tion. It may, however, be more economically ap- plied, and is frequently quite as effective, if di- rected to be put on cotton, applied to the affected surface and then covered with several layers of cloth or otherwise prevented from evaporating too rapidly. VOLATILE OILS. All the volatile oils are irritant, their action ranging from that of the mild sandalwood or copaiba oil to the extremely irritant volatile oil of mustard or even the caustic action of oil of cloves. The use of the milder members of this series for their effects on the urinary tract will be mentioned in connection with diuretics. Some of the volatile oils, such as pennyroyal and savin oils, which are somewhat more irritant, have been employed to produce abortion by reason of irritation of the in- testine and the consequent participation in the effects by the uterus. _ OFFICIAL PREPARATION'S. Of the official substances that are more or less RUBEFACIENTS. 165 closely connected with the turpentine group and are frequently used externally, we have : Oleum Rosmarini.- — U. S. — This is a volatile oil distilled from the fresh flowering tops of Ros- marinus officinalis and is one of the ingredients in the well-known soap liniment. Oleum Sabinua — U. S. — Oil of Savin has been quite extensively used as a local irritant. It must be used with caution in order to guard against the tendency to act as a vesicant. Oleum Terebinthiius — U. S. — Oil of Tur- pentine is the volatile oil distilled from turpen- tine. Even as an external application it is not in- frequently used in the form of Oleum Terebinthinae Bectificatum. — U. S. — This is identical with oil of turpentine in chem- ical properties, but it has a more agreeable odor. Terebinti-iina. — U. S. — This is officially de- scribed as the concrete oleoresin of Pinus palustris and of other species of Pinus. Resina. — U. S. — Rosin, resin or colophony is the residue left after distilling off the volatile oil from turpentine. The last two articles, rosin and turpentine, are interesting only as constituents of several official preparations, of which the best known are : Ceratum Resina. — U. S. — This is a cerate containing 35 parts of rosin, 15 parts of yellow wax and 50 parts of lard. Ceratum Resinae Compositum. — U. S. — This is a revival of the one-time official Deshler’s salve. It contains rosin, yellow wax, prepared suet, tur- pentine and linseed oil. Linimentum Terebinthin^:. — U. S. — This is a solution of 65 parts of resin cerate in 35 parts 166 PHARMACOPEIA AND PHYSICIAN. of oil of turpentine. It has been recommended to be used in place of the oil of turpentine as a local application when the action of the latter might be considered as too irritating. Oil of turpentine may be applied either in the form of the official liniment, diluted with a fatty oil, or it may be used in substance as a stupe; the latter is made by saturating a cloth with hot water, wringing it out and then dropping on it a little warm oil of turpentine, or dipping the moist cloth into the oil of turpentine and again wring- ing it out and applying while still warm. Local applications of this kind will be found useful in bronchitis. Great care must be taken in warming oil of turpentine, as its vapor is inflam- mable. It should be warmed by placing the bottle containing it, uncorked, in a vessel of hot water away from the fire. Plasters of Burgundy pitch, Burgundy pitch with cantharides and of resin were formerly of- ficial. In practice these old-time resin plasters have long since been replaced by the more modern rubber-base plasters. The best representative of the rubefacient plasters now in use is the Emplastrum Capsici. — U. S. — This is directed to be made by applying a thin coating of oleoresin of capsicum to adhesive plaster. CAPSICUM. Capsicum. — U. S. — The dried ripe fruit of Cap- sicum, fastigiatum constitutes one of the most pop- ular of the rubefacients used at the present time. Of the available official preparations we have : Fluidextractum Capsici. — V. S.— This is made with strong alcohol. R UHEFACIEXTS. 167 Tixctura Capsici. — U. S. — This is made with a mixture of 95 parts of alcohol with 5 parts of water, and represents 10 per cent, of the crude drug. Either of these preparations may be used diluted with alcohol or with soap liniment as a local rube- facient or irritant. Oleoresixje Capsici. — U. S. — This is made by extracting capsicum with acetone and may be used in the shape of the plaster, as noted above, or in the form of the now popular mixture with pe- trolatum. A typical prescription for a rubefacient of the latter type would be as follows : R. Oleoresini capsici gr. xv II Petrolati giii 100] M. Ft. unguentum. Sig. : Use locally. MENTHOL. Mexthol. — U. S. — This is a secondary alcohol obtained from the oil of Mentha piperita or other mint oils. This substance is very largely used in the form of pencils or cones, sometimes in alco- holic solution, rubbed on the skin in neuralgia. It causes a burning, and then a sensation of cool- ness. Camphorated Chloral. — IST. F. — This prepar- ation, cpiite popular in some parts of the United States as a local application, consists of equal parts of hydrated chloral and camphor. It is a thick, oily-looking liquid, which is extremely irri- tating. It may be diluted with the fatty oils, al- cohol or soap liniment. 168 PHARMACOPEIA AX D PHYSICIAN. MUSTARD. Mustard is official as: Sinapis Alba — IJ. S. — White Mustard is the seed of Sinapis alia. Sinapis Nigra. — XJ. S. — Black Mustard is the seed of Brassica nigra. Oleum Sinapis Volatile. — U. S. — This is a volatile oil obtained from black mustard (freed from its fatty oil) by maceration with water and subsequent distillation. Ciiarta Sinapis.— U. S. — Mustard Paper is di- rected to be made by coating rather thick, well sized paper with a mixture of rubber cement and powdered black mustard which has been deprived of its fatty oil. Mustard foot baths, containing one or two ounces of powdered or ground mustard, prefer- ably the black, thoroughly mixed with a gallon of warm water, are extremely useful for the relief of mild congestions of the head and of the gastro- intestinal tract. Prompt relief is often obtained in this way from headache and from pain in the stomach. In many cases, even mild attacks of indigestion show decided improvement almost immediately ; the action is further accelerated if a liot-water bag is placed over the region of the stomach at the same time. The feet should be placed in the bath while the legs and feet are briskly rubbed with the mustard water for ten minutes or until the skin is red and some irritation is felt. The extremities are then rubbed dry with a coarse towel and wrapped in flannel or a blanket. When a slight degree of RUBEFACIENTS. 169 counter-irritation is desired for some time, a mus- tard poultice is employed. This is made by mixing one part of the ground black mustard with about five parts of flour (or ten parts of flour in the case of children), and mixing with enough water to form a mass. This is then spread on cheesecloth and applied at once. Mustard poultices have been largely replaced by the much more convenient mustard papers, which are dipped in tepid water and applied at once. They are prone to become worthless in damp cli- mates, since the absorption of moisture causes the slow development of the volatile oil, which then evaporates as fast as it is formed. With proper precaution, however, they may be preserved for a considerable length of time, and they will usually be found to afford the most convenient means of applying counter-irritation. HEAT. The uses of heat are so numerous and so well known that they scarcely require further mention at this time. We may be permitted to call atten- tion, however, to some of the various forms of cataplasms or poultices that are frequently used for their rubefacient or irritant properties. Among the official substances that are frequently used for the preparation of poultices we have : Linum. — U. S. — Linseed or flaxseed is the ripe seed of Linum usiiatissimum. Ulmus. — U. S.- — Elm or slippery elm is the dried bark of Ulmus fulva, deprived of its peri- derm. Carbo Ligeti. — U. S. — This is charcoal pre- pared from soft wood and powdered. 170 PHARMACOPEIA AND PHYSICIAN. Poultices are ordinarily prepared by mixing the requisite amount of ground flaxseed, ground elm bark or other substance with enough boiling water to make a rather stiff mass, inclosing this in a piece of gauze or muslin and applying to the surface. The rubefacient properties of a poultice may be increased by the addition of ground mustard, tincture of capsicum or of oil of turpentine. For removing fetor or to act as disinfectants, poultices may have added to them powdered charcoal, chlor- inated lime or the official solution of chlorinated soda. The present edition of the United States Phar- macopeia has included one poultice, as : Cataplasm a Kaolixa. — U. S. — This consists of kaolin, glycerin and boric acid, with thymol, methyl salicylate and oil of peppermint as admix- ture to give it a pleasing odor. This preparation, like other poultices, is most efficacious when ap- plied hot, but, as its action depends to a very great extent on the r-ubefacient properties of undiluted glycerin, due precaution should be taken to pre- vent the absorption of water or of watery vapor during the course of preparation or when heating it preparatory to applying. Practically the same preparation is being of- ferred to the medical profession at the present time under a variety of trade names, and while the combination undoubtedly has uses, many if not all of the positive claims that are made in con- nection with it are, to say the least, somewhat ex- aggerated, and the preparation should not be ex- pected to accomplish more than might reasonably be expected from an equivalent application of heat and mild rubefacients. RUBEFACIENTS. 171 One other point in connection with this partic- ular preparation that has been the cause of some controversy in the advertising pages of medical journals is the question of priority. This question may safely be ignored, as the mixture, apart from the flavoring ingredients, can not be said to be new. Glycerin magmas have been known and used for upward of half a century, and a formula for practically an identical preparation may be found in the Pharmaceutical Journal, London, for March. 1858. Formic acid has long been known and used in domestic practice as a rubefacient. In Germany it has found considerable favor in regular medicine and is official in the German Pharmacopeia as a 24 per cent, solution and also as a spirit of formic- acid, the latter containing 4 per cent, of the official solution of formic acid in a mixture of alcohol and water. IODIX. The official preparations of iodin that are used as rubefacients are : Liquor Iodi Compositus. — L T . S. — This is bet- ter known as Lugol’s solution; it contains 5 per cent, of iodin and 10 per cent, of potassium iodid in water. Tinctura Iodi. — LT. S. — This is an alcoholic solution and contains 7 per cent, of iodin and 5 per cent, of potassium iodid. UxGUENTtJM Iodi. — LT. S. — This contains 4 per cent, of iodin and 4 per cent, of potassium iodid in a mixture of glycerin and benzoinated lard. Iodin in the form of the tincture or of the solu- tion is very commonly applied to the skin as a 172 PHARMACOPEIA AND PHYSICIAN. counter-irritant. Repeated applications produce a caustic effect, but the action is very easily con- trolled. One great disadvantage possessed by the official preparations of iodin is the dark staining of the skin. Numerous efforts have been made to obviate this by using so-called colorless tinctures of iodin, which are merely solutions of iodids. It is much better to apply the iodin until sufficient irri- tation is caused and then remove the stain by washing with dilute solution of ammonia water or with a solution of sodium thiosulphate. A more modern preparation of iodin that prom- ises to replace the official preparations as an ex- ternal application is a solution of iodin in sa- ponated petrolatum, a formula for which will be found in the latest edition of the National Formu- lary. Saponated petrolatum may be made by simply mixing : Liquid petrolatum 3ii 60 Oleic acid Si 30 Spirit of ammonia 3ss 15 In the order enumerated, the only necessary pre- caution being to use preparations that correspond to the requirements of the United States Pharma- copeia. This simple saponated petrolatum will readily dissolve iodin up to 10 per cent, of its weight. A 5 or 6 per cent, solution of iodin, however, will be found to be most useful and not too irritating. Probably the greatest advantage possessed by a preparation of this kind is due to the fact that it causes little or no stain and may be readily washed off with soap and warm water. Saponated petrolatum may also be used for ap- VESICANTS. 173 plying a number of other rubefacients, such as camphor, menthol, chloroform, methyl salicylate and turpentine. VESICANTS. Vesication is the result of greater irritation than that which merely causes rubefaction. The exu- date from the blood vessels is not absorbed, but collects beneath the horny layer of the skin, which it can not penetrate, but which it separates from the layers beneath. Such collections of fluid are called vesicles or blisters, and the agents which produce them are termed epispastics, vesicants or ‘^blisters.” If the vesicle is ruptured soon after it has formed, and the horny layer removed, it leaves a tender surface of the skin exposed; this is irri- tated even by contact with the air, and, being eas- ily permeated, it is liable to infection, hence it is better to puncture the blister with a sterile needle inserted at the periphery; the fluid is allowed to escape while the loose layer of epidermis is left in place for protection until a new hard layer is formed. While there is some sensory stimulation, vesica- tion may occur from slowly acting agents which do not penetrate readily, with merely an itching. Those agents which applied to the skin cause vesication also cause an irritation of the mucous membrane, but, as the exudate escapes more read- ily from such surfaces vesication does not usually occur. ATsicants, and, in fact, all but the mildest of irritants, such as heat, are contraindicted in the treatment of infants, in diabetics, who are prone to gangrene, and for the old and the feeble. 174 PHARMACOPEIA AND PHYSICIAN. The internal use of irritants which are excreted by the kidneys, and their external nse if they are absorbed, as sometimes occurs with cantharides, are to he avoided in nephritis ; in such cases stronger ammonia water may be used, but it is very painful. Mustard occasions so much pain before blister- ing, owing to the volatility of the oil of mustard, which, therefore, penetrates readily, that it is sel- dom used to produce an irritation beyond the stage of rubefac-tion. Cantharides contains cantharidin, which, though readily volatile at a higher temperature, is not much affected at the body temperature and does not rapidly penetrate the tissues, hence cantharides causes vesication with but little pain and is much the most popular of the vesicating agents. OFFICIAL PREPARATIONS OF CANTHARIDES. Cantiiaris. — U. S. — Cantharides, more popu- larly known as Spanish flies, is officially described as the thoroughly dried beetle of Cantharis vesica- toria. The powder of cantharides, which is the form of the drug that is most frequently found in the shops, is grayish brown in color with shining green particles. It should contain few or no hairs. Ceratum Cantharides. — IT. S. — Cantharides Cerate, also known as blistering cerate or blistering plaster, contains 32 parts of powdered cantharides in a mixture of liquid petrolatum, yellow wax, rosin and lard. Cantharides cerate is most fre- quently used in the form of a plaster, spread on the official adhesive plaster or some other suitable grease-proof material. Collodium Canthartdatum. — U. S. — Can- VESICANTS. 175 tharidal Collodion represents the chloroform sol- uble portion of 60 parts of cantharides dissolved in sufficient flexible collodion to make 100 parts. Tinctura Cantharides. — U. S. — This prepa- ration represents 10 parts of cantharides extracted with alcohol. It is not usually efficient as a vesi- cant, but is frequently used externally as an irri- tant or rubefacient. The active principle of cantharides is not soluble in water, and as the normal skin is usually covered with a thin film of perspiration, the necessary pre- cautions must be taken to have the blistering prep- aration come in contact with the dry skin. This is most readily accomplished by washing the part with soap and water and wiping it with a small amount of strong alcohol. In the case of the cerate or plaster the alcohol may be followed by a fatty oil, or, better still, the surface of the plaster may be thinly coated with a coating of oil. In directing the use of a blister it should be re- membered that the resulting vesicle is usually larger than the plaster that has been applied, and the size of the latter, therefore, should be gauged accordingly. Cantharidal collodion is simply painted on the surface, and is more cleanly than the cerate. In using blistering collodion the same precaution of thoroughly cleansing the skin, with soap and water, and alcohol, should be observed so as to insure vesication. Vesication usually ensues in about six hours after the application of the vesicant, but a some- what longer period may elapse even in cases in which all the necessary precautions have been ob- served. and the physician should allow ample time 176 PHARMACOPEIA AND PHYSICIAN. before he concludes that the preparation is worth- less. Oantharides is prone to deteriorate with age, and one is often inclined to attribute the failure to cause blistering, to the worthlessness of the pro- duct, but even a faultless preparation may at times fail to produce vesication. The now widely used rubber-base plaster con- taining cantharides, although not official, has many points of advantage over the less cleanly extem- poraneous plaster made from the cerate. After preparing the surface of the skin, as indicated above, the plaster is smeared over with a thin film of oil and applied at once. After causing sufficient vesication it can be removed readily, and in this respect offers some advantage over the blistering collodoin which continues to act until exhausted. While cantharides is commonly employed as a vesicant, it is sometimes applied for a shorter time to produce rubefaction, and its irritant action is also made use of in hair tonics, as it is supposed to stimulate the growth of hair. The following formula fairly represents the form of mixture commonly used as a hair tonic : IJ. Tinctura cantharidis f.3ii 81 Ammonii carbonatis 3i 4 Spiritus myrcise f.Sii 601 Aquse q. s. ad f.Svi 200 1 M. Sig. : Apply with brush, rubbing into the scalp after washing with tar soap. The expensive Packer’s tar soap has no ad- vantage over the very much cheaper tar soap gen- erally used by machinists for washing grease from the hands. VESICANTS. 177 Where an oleaginous preparation, containing cantharides, is desired, the following may be used: R. Olei ricini Tineturae cantharidis, aa f . 3ii 8 Spiritus myrciae f. gi 30 Alcoholis q. s. ad f. §vi 200 M. Sig.: Apply locally to scalp. The toxicology of cantharides is of some im- portance because the laity has an exaggerated idea of its efficiency as an aphrodisiac without a cor- responding appreciation of its harmful effects on the kidneys. Poison oak has been used as an irritant, but it is wholly unsuited for the purpose because of the extraordinary activity of the irritant principle, the uncertainty of its action, and the inability to control it, which render it far inferior to many other available irritants. It is of much greater toxicologic interest because of the frequency with which accidental poisoning occurs, either from handling it or merely coming into the immediate neighborhood, since even dust particles may carry enough of the extraordinarily active fixed oil, toxicodendrol, on which the action depends, to poison susceptible persons. Toxicodendrol penetrates the skin very easily and is, therefore, difficult to remove. Even bland oils are to be avoided in the treatment of poisoning by it, since they but serve to dissolve and spread the poison, the same being true, of course, of oint- ments, vaselin and cerates. In treating a case of rhus poisoning as much as possible of the poison should be removed by re- peated washing with soap and fresh portions of warm water, after which a paste of soap or a so- 178 PHARMACOPEIA AND PHYSICIAN. lution of lead acetate is applied. If vesicles form they should be opened with care and the liquid received on absorbent cotton or a powder such as baking soda, since it would but extend the irrita- tion if the exuding liquid were allowed to spread over the surface of the skin. The place should then be carefully washed with soap and warm water to remove even traces of the fluid from the vesicles, and the soap paste or the solution of lead acetate applied. Fluidextract of grindelia robusta, diluted with water, or with a saturated solution of sodiu m bi- carbonate (about 6 per cent.) has had a special reputation as a wash for the treatment of poison oak. PUSTULANTS. Pustulants are those irritants which give rise to pustules instead of vesicles. The pustulants ap- pear to be unable to affect the skin through the horny layer as a rule, but can only penetrate the orifices of the glands. They are much less fre- quently used than the rubefacients and the vesi- cants. As tartar emetic is not irritant except in acid solution it has been suggested that it is decom- posed by acids in the cutaneous glands, and there produces pustulation. Croton oil owes its irritant action to crotonoleic acid, which exists mainly in combination as a fat. This fat is not affected by the gastric juice, but is split up in the intestines and the crotonoleic acid is then able to exert its violent irritation result- ing in purgation. Applied to the skin croton oil causes pustula- PUSTULAXTS. 179 tion. It is not now so much used externally or internally as it was formerly. OFFICIAL PUSTULAjSTTS. Antimonii Et Potassii Tartras. — IT. S. — - Antimony and Potassium Tartrate, more commonly known as tartar emetic, is usually seen as a white granular powder, without odor, and having a sweet, afterward disagreeable metallic taste. It is soluble in about 16 parts of cold water, but is much more readily soluble in hot water. Antimony and potassium tartrate may be used externally, as a pustulant, either in the form of the powder, in aqueous solution, or in the form of an ointment. The German Pharmacopeia contains a formula for the latter preparation that appears to be quite popular on the continent of Europe. This is a simple mixture of 20 parts of antimony and potassium tartrate, with 80 parts of petrola- tum. Because of its irritant action tartar emetic pro- duces nausea or emesis, when taken internally, ac- cording to the amount employed. It is much more frequently used as a nauseant than as an emetic, and least often as a pustulant; for the latter pur- pose it will be found to be preferable to use it in the form of an ointment, similar to the one re- ferred to above, simply rubbed on the skin. Oleum Tiglii. — U. S. — Croton oil is described as a fixed oil expressed from Croton Tiglium. It occurs as a pale yellow, or brownish yellow viscid, fluorescent liquid, having a mild, oily, afterward acrid and burning taste. In eastern countries croton oil appears to have been known from a very early period. It was known in Europe sev- 180 PHARMACOPEIA AND PHYSICIAN. eral centuries ago, but fell into disuse and was reintroduced there with several other drugs from India, about 1813. CAUSTICS. , Caustics are irritants which either cause violent inflammation, resulting in necrosis, or dissolve the tissue by direct chemic action. Caustics may be used to produce counterirrita- tion alone, to remove exuberant or diseased tissue, or, in diluted form, to stimulate non-granulating surfaces. Apart from the use of the thermo-cautery in surgery, that of lunar caustic for exuberant growths and non-granulating tissues, and of ar- senic for the destruction of the nerves of teeth, caustics are not very widely used at the present time. The number of substances possessing a corrosive action is of course very great, but many of them are not suited for therapeutic use, thus the strong alkalies, such as caustic potash and caustic soda, dissolve the tissue and penetrate deeply, hence their action is not easily controlled, besides they are very painful. Potassium hydroxid, better known, perhaps, as potassa, is sometimes used to soften and to remove the callous of corns and warts. The action of silver nitrate, and of copper sul- phate, in the form of molded sticks, or cones, is so easily controlled that they are very commonly used. Akgenti Nitras. — XL S. — Silver Nitrate ap- pears to have been known to Geber as lapis in- fernal] s in the eighth century, and has been used extensivelv since that time. It occurs as colorless CAUSTICS. 181 crystals, which are freely soluble in about one part of water and melt or fuse at 200° C. (392° F.). This latter feature is taken advantage of in making the official forms of fused silver nitrate, and is also of advantage in forming extemporane- ous preparations, for local application, by melting or fusing silver nitrate on to suitable metallic in- struments such as sounds. Argenti Nitras Fusus. — U. S. — Molded Silver Witrate contains about 95 per cent, of silver nitrate,- with a small amount of silver chlorid, which is added to make the sticks tough and fibrous. Argenti TTitras Mitigates — U. S. — Miti- gated Silver Xitrate is composed of one part of sil- ver nitrate and two parts of potassium nitrate fused together. Cupri Sulphas. — IT. S. — Copper Sulphate or blue vitriol occurs as large, transparent deep blue crystals. For external use these crystals may be rasped or filed into suitable shape, and are then used in very much the same way as are the sticks of silver nitrate. The various uses of these agents are so well known that they scarcely require extended treat- ment here. When the lunar caustic is used on exuberant granulations care should be taken to avoid bring- ing it into contact with the newly formed skin, which is recognized only as a bluish line, since this occasions pain and is, of course, destructive of the very object it is intended to promote. ARSENIC AND ZINC CHLORID. Arseni Trioxidum. — IT. S. — Arsenic Trioxid, 182 PHARMACOPEIA AND PHYSICIAN. also known as arsenous acid and as white arsenic, occurs most frequently as an odorless, and taste- less white powder, that is but slowly soluble in about 100 parts of water. Ziftci Chlokidum. — U. S. — Zinc Chlorid oc- curs as a white granular powder or a porcelain- like mass. It is freely soluble in water, but the solution decomposes, on long standing or boiling, depositing a basic salt. Arsenic and zinc chlorid have been used to de- stroy cancerous growths. Arsenic, particularly, has been widely used as the active constituent of various cancer cures that have been proposed by regular, as w r ell as irregular, practitioners. Its action is very slow, and therefore it can be readily controlled, but it occasions considerable pain. Arsenic may be employed in the form of powder, as an ointment, either with lard or petrolatum, or as a paste. In the latter case the arsenic is suitably diluted with either starch or powdered althaea, and subsequently mixed with water to which a trace of gum or mucilage has been added. At present arsenic is most frequently used for the destruction of the nerves in carious teeth. Zinc chlorid is now but seldom used for its local corrosive action. It may be used in aqueous solu- tion or fused on to suitable metallic instruments, much as silver nitrate is employed. Mercuric chlorid is the most corrosive of the metallic salts, but it is too toxic to permit of its general employment for its local caustic action. SOME OTHER OFFICIAL CAUSTICS. Acidum ISTitricum.— U. S. — The official Xitric- Acid contains G8 per cent, by weight, of absolute EMOLLIENTS. 183 nitric acid, and occurs as a colorless, fuming liquid that is very caustic and corrosive. Liquor Hydrargyri ISTitratis.— U. S. — Solu- tion of Mercuric Nitrate occurs as a clear, nearly colorless liquid, having a faint odor of nitric acid and a strongly acid reaction. It should contain about 60 per cent, of mercuric nitrate and about 11 per cent, of free nitric acid. Unguentum Hydrargyri Nitratis — U. S. — Ointment of Mercuric Nitrate is made by dissolv- ing 7 parts of mererny in 10.5 parts of nitric acid and adding this solution to 76 parts of lard that has previously been partially decomposed by 7 parts of nitric acid, and continuing the heat, if necessary, until the reaction is completed. The re- sulting ointment should have a bright yellow color, whence its popular name, “citrine ointment.” Unguenttjm Hydrargyri Ammoniati. — IT. S. — The Ointment of Ammoniated Mercury is now directed to be made by mixing 10 parts of am- moniated mercury with 50 parts of white petro- latum and 40 parts of hydrous wool fat. Nitric acid is a popular domestic remedy for the removal of warts. The surrounding surface should be thickly covered with petrolatum and a single drop at a time of the acid applied to the excresenee. EMOLLIENTS. The word emollient is derived from emollio , to soften ; demulcent comes from demulceo , to smooth. Since the same agent is usually demulcent as well as emollient, the term to be used depends on the tissue to which the agent is to be applied, rather than on the medicinal agent itself. Mucous 184 PHARMACOPEIA AND PHYSICIAN. membranes rarely require softening, but an in- flamed skin is frequently hard and rough, we therefore speak of applying demulcents to mucous membranes and emollients to the skin. Not only bland oily substances and fats, but mucilages and diluted glycerin act as emollients. Glycerin, when diluted with water, and rubbed into the skin, prevents it from becoming dry and harsh, and the tendency to crack. Oils and fats penetrate the skin and render it soft. SOME OFFICIAL EMOLLIENTS. Adeps Lan^e IIydrosus. — U. S. — This prepara- tion, formerly called lanolin, is the purified fat of the wool of sheep (Ovis dries), mixed with about 30 per cent, of water. Glycerinum.- — U. S. — Glycerin or glycerol is a clear colorless liquid of syrupy consistence, .ob- tained by the decomposition of vegetable or animal fats. Anhydrous glycerin is slightly rubefacient, but when diluted, as noted above, is an efficient emollient. Mucilago Tragacanthle. — II. S. — Mucilage of Tragacanth contains 6 per cent, of tragacanth and 18 per cent, of glycerin, with enough water to make 100 parts. Petrolatum. — U. S.- — Under this general head- ing the present Pharmacopeia includes what was formerly known as hard and soft petrolatum. Petrolatum, a mixture of hvdrocarbons, of the V.: GO . . r methane series, is obtained from petroleum and should be of about the consistence of an ointment. The official substance may vary in color from yel- low to light amber and have a melting point vary- ing from 45° to 48° C. (113° to 11S.4° F.). in EMOLLIENTS. 185 ' addition to this, which is popularly known as yel- low petrolatum, the Pharmacopeia also includes : Petrolatum Album. — U. S.— This is a white unctious mass, of about the consistence of oint- ment, that otherwise has the same chemical and physical characteristics as petrolatum. Petrolatum Liquidum. — TJ. S. — Liquid Petro- latum is a colorless or only slightly yellowish, oily transparent liquid without odor or taste, but giv- ing off. when heated, a slight odor of petrolatum. Of the vegetable oils that are useful as demul- cents, it will suffice to enumerate : Oleum Amygdala Expressum. — U. S. — Ex- pressed Oil of Almonds. Oleum Gossypii Seminis. — TJ. S. — Cotton Seed Oil. Oleum Olhle. — TJ. S. — Olive Oil. Oleum Theobromatis.— TJ. S.- — Oil of Theo- broma, so-called “cocoa” butter. Of the several official preparations of this class by far the most popular is : TJnguentum Aqu^e Rosm:. — TJ. S. — Ointment of Rose Water, or, as it is usually called, cold cream. This ointment consists of a mixture of spermaceti, white wmx, expressed oil of almonds, sodium borate and rose water, and in one form or another has been the most popular of the mild emollients from the time of its originator, Galen. Emollients are used for the protection of in- flamed skin against irritants, the choice depending on individual preference or convenience rather than on the nature of the drug. Thus mucilage of tragacanth, ointment of rose water and petrolatum differ widely in their physical properties, but they 186 PHARMACOPEIA AX D PHYSICIAN. are all used for chapped hands, sunburn, and to soften the skin when it is rough and hard. The bland oils and ointments penetrate the skin more readily than does diluted glycerin, and, therefore, they are to be preferred as emollients when they are also to serve as carriers of medicinal substances intended for absorption. Diluted glycerin is an excellent agent for soft- ening the skin, but is somewhat irritant, and when the sensitive layers of the skin are exposed, a bland oil or ointment, such as cold cream, is to be pre- ferred. To prevent chapping of the skin when it is ex- posed to the wind, to alternate wetting and drying, or to irritants, the mucilage of tragacanth, pre- ferably mixed with an equal portion of glycerin, will be found useful. The exposed surface is washed with warm water and soap to soften the skin, and while it is still moist, but not wet, a little of the mucilage, or the mixture of mucilage and glycerin, is rubbed into the surface until the latter feels smooth. Instead of the tragacanth mixture the following may be preferred by some, but it is somewhat irritant to very delicate skin : One ounce of glycerin soap is reduced to shav- ings and dissolved with the aid of gentle heat, in half a pint of a mixture of equal parts of glycerin and water. This mixture solidifies on cooling, and a piece about twice the size of a pea is to be rubbed into the moist skin as often as may be necessary. Those who work with irritant or corrosive chemi- cals will find this an excellent agent for keeping the hands soft. A liquid preparation that has met with consid- erable favor may be made by mixing ten parts of EMOLLIENTS. 187 tincture of benzoin, fifty parts of water, and forty parts of glycerin. To secure a homogeneous mix- ture the water should be gradually added to the tincture of benzoin, and the glycerin added to this mixture. If the resulting mixture should still be irritating the amount of glycerin may be further reduced, with a corresponding increase in the quantity of the water. If rose water were substi- tuted for the water in the above formula the re- sulting mixture would simulate some of the well known and widely advertised proprietary toilet preparations of glycerin and roses. CHAPTER VII. LOCAL ANESTHETICS AND ANODYNES. The introduction of cocain marked a decided ad- vance in the production of local anesthesia. Previous to that, freezing the part by immersion in a mixture of salt and snow, or shaved ice, or by spraying with ether or other volatile liquid, was used, and while a procedure of this kind does pro-, duce complete anesthesia, the pain experienced during the freezing and thawing greatly exceeds that which would be caused by such a simple operation as opening an abscess or the removal of a small foreign body, such as a splinter or piece of glass, when readily accessible. It is because of the inherent dread which the average person has of the surgeon’s knife, that he will undergo suffering akin to that with which he is familiar, rather than endure a lesser one which seems dreadful because it is unfamiliar. It is also true that the injection of cocain some- times causes more pain than would the operation for which it is given, and, since surgical operations have become so much more common than they were formerly, many adults willingly bear the brief, sharp pain of a simple incision, rather than resort to cocain, which has come into a certain disrepute because of the abuse of it by its victims, the ma- jority of whom have become such through the use of supposedly harmless nostrums pretending to be valuable remedies for hay fever and other minor affections. LOCAL ANESTHETICS. 189 Cocain, which is benzoyl ecgonin, shows a cer- tain chemical analogy to atropin and aconifin, which resemble it somewhat in their action on sensory nerves, and it is also related to phenol through the benzoyl group, since benzoic acid dif- fers from phenol only by having a COOH group in place of the OH of the phenol. The anesthetic action of phenol is second only to that of cocain. Aside from the systemic effect, which we need not fully detail here, cocain paralyzes sensory nerve endings with which it comes in contact and even nerve trunks when in sufficient concentration; if the solution is sufficiently dilute and the action not too long continued, the nerve endings rapidly re- turn to normal (the nerve trunk more slowly), when the application is discontinued and the co- cain removed by absorption into the general circu- lation, or evacuated. When a fairly strong solution (3 per cent.) is injected into the area about a nerve trunk, or an even weaker solution, 2 per cent., within the nerve sheath, both sensory and motor paralysis occur in about fifteen minutes, affecting, of course, the en- tire distribution of the nerve, the effect lasting for some hours after intraneural injection. Since aqueous solutions are not absorbed from the unbroken skin, they must be injected beneath the epidermis, at least, in order that they may come into actual contact with the nerve ends. When the solution is injected deeply into the muscular tissue the greater part of it passes into the general circulation and is lost so far as local action is concerned. To avoid this, it is better to inject the solution between the layers of the skin, at the same time limiting the circulation in the 190 PHARMACOPEIA AND PHYSICIAN. part as much as possible by compressing the blood vessels, preferably with a rubber band or other tight bandage. Practically, the same object may be achieved by the use of a solution of the alkaloid of the supra- renal gland immediately preceding the injection of the solution of cocain. The injection of the solu- tion of suprarenal alkaloid (epinephrin, adrenalin or one of the other trade preparations) causes a local vasoconstriction that in turn prevents the rapid absorption of the cocain solution into the general circulation, and also prevents, for the time being, the excessive hemorrhage that is so objec- tionable in minor operations. When it is neces- sary for the solution of cocain to diffuse through a part, a moment should elapse after the injection before applying the constricting bandage. The combined use of suprarenal alkaloid and of cocain has proved to be of particular advantage in the eye and in the nose. One reason, and prob- ably the most weighty one, is to be found in the fact that normal mucous surfaces have a tendency to absorb cocain verjr rapidly. When cocain is applied to mucous membranes, either in powder or in solution, it causes its local effects for a short time and is then absorbed, pro- ducing its systemic action. Herein lies one of the chief sources of danger of the many so-called hay- fever remedies, which virtually consist of cocain with some diluent powder, such as sugar of milk, and are intended to induce and to continue the truly terrible cocain habit. Owing to the brief action and rapid absorption, frequent repetition is necessary to secure relief in “colds” and the user is peculiarly liable to become LOCAL ANESTHETICS. 191 addicted to the habit which, in its baneful effects, is not exceeded perhaps, in the whole range of drug addiction, not even excepting alcoholism. As a matter of fact, many of the so-called hay-fever nostrums are intended primarily for supplying those who are already victims of the habit and who would find difficulty in buying the drug under its real name. This practice may be said to consti- tute a disgraceful example of the lack of control of the nefarious nostrum traffic by the law. We should be particularly careful to warn patients and others against the insidiousness of this type of self medication that our skirts may at least be kept clean in connection with this one phase of the evil. Cocain in solution is readily decomposed on boiling, but if the solution be made with sterile, cold water there will be little cause to anticipate sepsis from its injection with the usual precau- tions. The solution may be sterilized, however, by heating to 80° C. (176° F.) for half an hour at a time on two successive days, care being taken to eliminate all possible contaminations of even a trace of alkali. Eucain and stovain have the advantage of resist- ing decomposition by boiling, but, as just sug- gested, the disadvantage possessed by cocain is more apparent than real, and the general action of cocain, particularly its possible complications, being well known, that drug, no doubt, will con- tinue to hold first place as a local anesthetic, ex- cept where the ubiquitous detail man succeeds in frightening the more timid members of the profes- sion into an exaggerated idea of the various dangers attending the proper use of the official article, and 192 PHARMACOPEIA AND PHYSICIAN. into a corresponding credulousness concerning the entire harmlessness of the particular substitute in which he is interested. Cocain, when dropped into the eye, or taken in- ternally, causes an incomplete dilatation of the pupil by stimulating the sympathetic nerve, reac- tion to light being maintained, differing therein from atropin, which abolishes this reflex. OFFICIAL PREPARATIONS OF COCAIN. Cocaine Hydrochloriduai. — II. S. — Cocain Hydrochlorid, the most widely used preparation of cocain. is officially described as the neutral hydro- chlorid of an alkaloid obtained from several vari- ties of coca. It occurs as colorless, transparent crystals or a white crystalline powder. It is soluble in less than one part of cold water and in 2.6 parts of alcohol, but is insoluble in petroleum benzin and in ether. Cocain. — U. S. — This is an alkaloid obtained from several varieties of coca, resembling cocain hydrochlorid in many of its properties, but being only slightly (1-600) soluble in water. It is soluble in 5 parts of alcohol and even more soluble in ether and in petroleum benzin. The alkaloid co- cain is also soluble in about 12 parts of olive oil and it, or the oleate, is to be used in making solu- tions of cocain in oil. • Oleatum Cocaine. — U. S. — Oleate of Cocain contains 5 per cent, by weight of cocain in a mix- ture of oleic acid and olive oil. The liquid preparations of coca, the fluid extract and the wine, are never used externally, although, if applied to the mucous surfaces, or to the abraded skin, their use would not be devoid of danger, from LOCAL ANESTHETICS. 193 the absorption of the contained cocain, and other coca alkaloids. Cocain is used locally on mucous membranes to allay irritation and inflammation as in hay fever, but it should be used very guardedly and not be too long continued. It is very much less useful in this condition than was formerly supposed and it has been very largely replaced by the now com- monly used alkaloid of the suprarenal gland, which, it is claimed, allays the inflammation equally well and has the marked advantage of not inducing the habit. Solution of cocain is very commonly injected hypodermically, to produce local anesthesia during such slight operations as the evacuation of ab- scesses, the removal of splinters, bullets, and other foreign bodies. When there is considerable inflammation and ex- treme tenderness, stronger solutions are required than when a healthy surface is to be incised. In the former case, a syringe having a long, fine needle, is filled with a 4 per cent, solution of cocain hydrochlorid, the needle is then inserted obliquely, or almost parallel with the surface, between the layers of the skin, beyond the zone of increased tenderness, and a small drop of solution is forced beneath the epidermis; a white spot is seen in a moment and the needle is then advanced through that toward the more tender area without removing the point of the needle from beneath the epidermis : with each advance a drop of the solution is in- jected. When the needle has been passed under the epidermis for its full length, it is withdrawn and the point inserted into the most advanced blanched area ; in this way, using a curved needle, 194 PHARMACOPEIA AND PHYSICIAN. a complete circuit may be made of the seat of in- flammation. The object of injecting the solution between the layers of the skin is to secure anesthe- sia with a minimum of absorption into the general circulation The psychic effect on the patient of having pain- less injections made into such an extremely tender region tends to allay the nervous dread of the knife, which is a more important factor, than we, who are accustomed to seeing pain, are apt to realize. The injection of a solution of cocain into the hand is apt to prove ineffective when the trouble is deep seated, as in palmar abscess, and in such cases it is better to inject a small amount of a 2 or 3 per cent, solution around or into the nerve trunks in the forearm. The injection of strong solutions into nerve trunks has given rise to much trouble and it is preferable, therefore, to try to secure the effects from weak solutions. Anesthesia involving all the body below the site of the injection, may be secured by injecting about ten or fifteen minims of a 2 per cent, solution of cocain hydrochlorid into the subarachnoid cavity through a sterilized platinum needle which is in- serted at the side of the fourth lumbar vertebra. The patient must be placed in a sitting position, in order that gravity may not favor the passage of the solution up to the medulla. This method of using cocain (or any othetr drug) . is attended with so much danger that it is not justifiable except when for some reason, general anesthesia is not practicable. The anesthesia is induced in ten or fifteen min- LOCAL ANESTHETICS. 195 utes, with cocain, but its duration is very variable, lasting from half an hour to five hours. When the application of a constricting band is not feasible the previous injection of a solution of the suprarenal gland, as previously suggested, will delay the absorption of the solution of cocain into the general circulation. It should be remembered, however, that the use of a vasoconstrictor only de- lays and does not prevent the absorption of the co- eain. When a 'large amount of the cocain so- lution is necessary it will probably be prefer- able to use the infiltration method as proposed by Schleich. It is difficult to see what advantage is to be gained by the addition of morphin to a solution instead of directing the injection of the desired amount at once so as to secure its systemic effect. Schleich recommended solutions containing from 0.01 gm. (1/6 grain) to 0.2 gm. (3 grains) of cocain hydrochlorid and from 0.005 gm. (1/12 grain) to 0.25 gm. grain) of mor- phin hydrochlorid in 100 c.c. (3 fluid ounces) of 0.2 of 1 per cent, solution of sodium chlorid to which was added one-fourth of a drop of phenol. Strong solutions of cocain should not be used in carious teeth, and only small amounts of the weak solution. One or two drops of a 1 per cent, solu- tion often affords relief from toothache. Cocain is sometimes applied to hemorrhoids to lessen the pain and it may be said that its local use is much more rational than is that of opium, since the alkaloid morphin has no local analgesic or vasoconstrictor action, a fact to be remembered when prescribing urethral injections, and lotions for inflamed surfaces of the skin. Cocain has also been used, in small doses, to re- 196 PHARMACOPEIA AND PHYSICIAN. lieve nausea. It may be given alone or with other antiemetics. The following is an example of a combination with cerium oxalate, the latter being used empircally. R. Cocain* hydrochloratis gr. i 0106 Cerii oxalas gr. xvi 1 Aquae aurant. flor f. gi 30 1 M. Sig. : Shake the mixture and give one teaspoonful every half hour when needed. Many substitutes for cocain, of greater or less merit, have been brought forward by manufac- turers, and while they have been widely heralded as being superior to cocain, they are not free from disadvantages; though the manufacturers have not, as yet, devoted much time or space to the exploitation of these several disadvantages or dangers. Their further consideration, however, does not belong in a treatise on the Pharmacopeia. THE ATROPIN GROUP. Atropin, which will be mentioned among the analgesics, act locally as an anesthetic, its effects resembling those of cocain, but being weaker. Atropina. — U. S. — Atropin is officially de- scribed as an alkaloid obtained from Atropa Bel- ledonnn and from other plants of the same fam- ily. As it occurs in commerce, it is usually con- taminated by a small amount of hyoscyamin from which it can not be readily separated. Atropin is soluble in 450 parts of water and in 1.5 parts of alcohol. It is very poisonous, the average dose being 0.0004 gm. (1/160 grain), and it should, therefore, be tasted with the utmost cau- tion and only in dilute solution. ■ Atrophy Sulphas. — U. S. — This is the sul- LOCAL ANESTHETICS. 197 phate of the alkaloid atropin. In its physiologic properties and dose, atropin sulphate corresponds closely to atropin. It is soluble in less than one part of water and in about four parts of alcohol. Oleatum Atropina.— U. S. — Oleate of Atro- pin is a mixture of equal parts of oleic acid and olive oil containing 2 per cent, of atropin, in solu- tion. Extractum Belladonna Foliorum. — U. S. — Extract of Belladonna Leaves is directed to be made with a menstruum consisting of two parts of alcohol and one part of water, and should contain, when assayed according to the process given in the Pharmacopeia, 1.4 per cent, of mydriatic al- kaloids. Unguentum Belladonna. — U. S. — Belladon- na Ointment contains 10 per cent, of extract of belladonna leaves in a mixture of hydrous wool fat and benzoinated lard. Ehplastrum Belladonna. — U. S. — Belladon- na Plaster is now directed to be made by mixing 30 parts of extract of belladonan leaves with 70 parts of adhesive plaster, and corresponds closely with the widely used, commercial, rubber-base plasters. It is further directed that spread bella- donna plasters should yield, when assayed by the process given in the Pharmacopeia, not less than 0.38 nor more than 0.42 per cent, of mydriatic alkaloids. Eluidextractum Belladonna Badicis. — E. S. — Fluidextract of Belladonna Boot is directed to be made with a mixture containing four parts of alcohol and one part of water, and should yield, when assayed by the process given in the Phar- 198 PHARMACOPEIA AND PHYSICIAN. macopeia, 0.5 per cent, of mydriatic alkaloids from belladonna root. Linimentum Belladonna. — U. S. — Belladon- na Liniment is virtually a solution of five parts of camphor in a sufficient quantity of fluidextract of belladonna to make 100 parts. Fluidextractum Stramonii. — U. S. — This is directed to be made from the leaves of Datura Stramonium with a menstruum containing two parts of alcohol and one part of water. The fin- ished fluidextract is required to contain 0.35 per cent, of the mydriatic alkaloids from stramonium. Extractum Stramonii. — TJ. S. — Extract of Stramonium is made by evaporating the fluidex- tract to the required consistency, and should con- tain 14 per cent, of mydriatic alkaloids. Unguentum Stramonii.— IT. S. — Stramonium Ointment contains 10 per cent, of extract of stram- onium in a mixture of hydrous wool fat and ben- zoinated lard. Atropin and the extracts of belladonna and of stramonium, in the form of ointments, belladonna plaster and belladonna liniment are very common- ly employed as local applications for the relief of the various neuralgias. The members of the atro- pin group are said to be more efficacious in facial than in other neuralgias, but they are also used for the intercostal variety and for lumbago. Belladonna plasters are very commonly used, particularly by the laity, for a variety of pains, often serving merely to protect the surface, or for the retention of body heat. Suppositories of extract of belladona are fre- quently used with benefit in the treatment of hemorrhoids. LOCAL ANESTHETICS. 199 They may be directed somewhat as follows : R. Extra eti belladonnse fol grs. i 1 06 Olei theobromatis 3ii 8| M. Ft. suppositoria No. viii. Sig. : One every four hours, as directed. Belladonna ointment may be used for the same purpose. It may be directed to be spread on a little cotton which is placed in contact with the piles and they are then replaced in the rectum. If they still tend to protrude a pad of cotton is placed over the anus and held in position by a bandage. For men the bandage may be attached to the sus- penders, both back and front, when the severity of the attack is not such as to compel the patients to lie down. It must be remembered that the extract of bel- ladonna, whether applied as a suppository or oint- ment, is rapidly absorbed and the amount so used must not exceed the therapeutic dose. ACONITE. Aconite owes its action almost entirely to aconi- tin, an alkaloid which, like cocain, is composed of a base united to an aromatic acid. Closely re- sembling aconitin in its local action is veratrin. They both cause irritation w r hen applied to the mucous membrane. The effect of aconitin when taken by the mouth is very characteristic, the local effect being a tin- gling and then a disagreeable sensation in the throat which has been variously termed itching or “scratching.” Applied to the skin aconitin causes sensory stimulation, which is succeeded bv local anesthesia without the production of rubefaction. 200 PHARMACOPEIA AND PHYSICIAN. Aconitin is much less efficacious than cocain as a local anesthetic, and, of course, its injection is wholly inadmissible, but it is much more useful in the form of a liniment which is to be applied to the unbroken skin, through which aconitin may pene- trate to a slight extent. Aconitine — U. S. — An alkaloid obtained from the official aconite, the tuberous root of Aconitum napellus. There are a number of closely related species of aconite that contain alkaloids which differ widely in their physiologic action and dose. The now official aconitin is the purified crystalline alkaloid of the official root and should not be con- founded with the amorphous alkaloid formerly official or with any one of the more potent alka- loids obtained from other species of aconite. Aconitin is soluble in 3,200 parts of water and in 22 parts of alcohol. On account of the poison- ous character of this alkaloid it should never be tasted, except when in very dilute solution. Average dose: 0.00015 (0.15 mg. or 1/400 grain). Fluidextractum Aconite — IT. S. — Fluidex- tract of Aconite is directed to be made from the powdered root of Aconitum napellus with a men- struum composed of three parts of alcohol and one part of water. It should contain no less than 0.4 per cent, of aconitin. Tinctura Aconite — U. S. — This tincture now represents 10 parts of the crude drug, instead of 35 parts, as formerly official. It is made with a menstruum containing 7 parts of alcohol and 3 parts of water, and the finished tincture should contain 0.045 per cent, of aconitin. LOCAL ANESTHETICS. 201 YERATRIX. Somewhat closely related to aconitin, in its vari ous properties and uses, is veratrin, which is offi- cial in several well known forms. Yeratresta. — TJ. S. — The official Veratrin is a mixture of alkaloids obtained from the seeds of Asagrcea officinalis. It occurs as a white or a grayish-white amorphous powder that is soluble in about 1,750 parts of water and in 2.2 parts of alcohol. Oeatuat Yeratrixjl — TJ. S. Oleate of Yera- trin contains 2 per cent, of veratrin in a mixture of equal parts of oleic acid and olive oil. IJxguextum Yeratrixee. — pi. S. — Yeratrin Ointment contains 4 parts of veratrin with 6 parts of expressed oil of almonds and 90 parts of ben- zoinated lard. LOCAL USES OF ACOXITIN. Aconitin is sometimes used locally in the form of an ointment (from 1 to 100 to 1 to 500), or in the form of an oleate, made similarly to the offi- cial oleates of atropin or of veratrin, of 2 per cent, strength, for the relief of rheumatism and neu- ralgia. Inasmuch as it is absorbed in these forms from the unbroken skin, and much more rapidly from wounds or mucous membranes, it must be used with caution. For facial neuralgia it may be prescribed as follows : R. Aeonitini gr. iii Alcohol q. s. to dissolve Adipis 3iv M. Ft. unguentum. Sig. : Apply a very little of the ointment over the seat of the pain. 202 PHARMACOPEIA ARB PHYSICIAN. The fluidextract of aconite may be further con- centrated and used in the form of an ointment, or it or the tincture of aconite may he used as a lini- ment, applied on cloth, and a hot pad or water bot- tle laid over the surface. For muscular rheumatism a liniment composed of equal parts of the tincture, or a corresponding amount of the fluidextract and soap liniment may be rubbed on the surface, or, if desired, this lini- ment may be further varied by the addition of chloroform liniment, or other alcohol soluble rubefacient in place of the soap liniment. The following is the formula recommended by Magitot for toothache. IJ. Tincturae aconiti Chloroformi, aa m. xlv 3 Tincturae benzoini m. cl 10 M. Apply as needed. PHENOL. Phenol, or carbolic acid, has been considered under the subject of antiseptics. Applied to the skin, pure or in concentrated so- lution, it causes tingling and some pain with the formation of a white eschar and a rapidly induced partial or complete anesthesia of the part. It is so prone to absorption when weak solutions are used that its usefulness is interfered with to a great extent. Phenol. — U. S. — The Acidum Carbolicum of former pharmacopeias occurs as separate needle- shaped crystals or as a white crystalline mass that is soluble in about 20 parts of water, but is freely soluble in alcohol, glycerin or in fixed or volatile oils. Phenol will absorb or dissolve from 15 to LOCAL ANESTHETICS. 203 20 per cent, of water, and then occurs as a color- less or slightly reddish liquid. Phenol Liquefactum. — U. S. — Liquefied Phe- nol should contain not less than 86.5 per cent, by weight, of absolute phenol and about 13.6 per cent, by weight of water. Glyceritum Phenolis. — U. S. — Glycerite of Phenol consists of 20 parts of liquefied phenol and 80 parts of glycerin, by measure. TJnguentum Phenolis. — TJ. S. — Ointment of Phenol is now directed to contain 3 per cent, of phenol, in white petrolatum. Phenol is rarely if ever used for the production of anesthesia preliminary to incising the skin, but, in the form of the glycerite or, preferably, the ointment, it is very useful in allaying the pain of small ulcers and burns. It may momentarily in- crease the pain, but this is soon followed by less- ened sensibility. It is, of course, obvious that the use of phenol is not permissible where large surfaces are to he treated. When antisepsis is not of especial importance the ointment is to be preferred, as the continuous application of even comparatively weak aqueous solutions to the extremities has caused gangrene. CHAPTER VIII. GENERAL ANESTHETICS. The subject of general anesthesia concerns the surgeon much more than it does the physician, but, as in the matter of antisepsis, the physician must have some knowledge of this subject, and we shall, therefore, briefly consider the more important members of the group of general anesthetics, their uses and their probable limitations. Narcotics have been used from time imme- morial, for producing unconsciousness during sur- gical operations, but nitrous oxid has been in use longer than any other agent now employed for in- ducing general anesthesia. It is more than 100 years since Sir Humphrey Davy first suggested this use for nitrous oxid, but his suggestions met with no response, and it was not until many years later, in 1844, that Horace Wells, a dentist of Hartford, Conn., employed it for that purpose and thus in- troduced what he was pleased to term “ a new era in tooth-pulling.” It was at one time supposed that nitrous oxid caused unconsciousness merely through asphyxia, and while this is a very important factor, it has been shown that nitrous oxid also causes a depres- sion of the central nervous system resembling that of the methane derivatives such as chloroform and ether, and complete anesthesia has been produced without asphyxia by using a mixture of oxygen and nitrous oxid under pressure. This would probably constitute an ideal method of inducing GENERAL ANESTHETICS. 205 anesthesia were it not for the mechanical difficul- ties and the expense that it necessarily involves. Nitrous oxid is usually administered only for a short time, it being necessary to discontinue it so soon as marked cyanosis of the face occurs, after which the anesthesia lasts for about a minute or two. It is the safest agent which we possess for general anesthesia, the death rate being approxi- mately one in half a million cases, but aside from its use in dentistry and for inducing unconscious- ness preliminary to other anesthetics, its applica- tion is extremely limited. It is impossible to estimate the value to man- kind, and to surgery in particular, of the introduc- tion of anesthetization with ether by Morton and Jackson just fifty years ago. Its use by Dr. Craw- ford W. Long, in Georgia, antedates by more than two years the real work of Morton and Jackson in introducing the method, but the greatest credit is due those men for their splendid achievement in gaining general recognition for this boon to hu- manity. Shortly after the introduction of general anes- thesia by the use of ether Sir J. Y. Simpson an- nounced his discovery of the use of chloroform as an anesthetic, and this latter agent soon dis- placed ether almost entirely in many parts of the world. Even at present chloroform is used almost exclusively in several European countries. From time to time other agents have been pro- posed as substitutes for chloroform and ether, and some of them have enjoyed a greater or less popu- larity for a time, only to sink into obscurity. In this connection we may mention a few of 206 PHARMACOPEIA AND PHYSICIAN. those which will he remembered even by the younger generation of physicians, and which have not yet fallen into complete disuse. Ethyl bromid and bromoform have been used to some extent as general anesthetics, and it has been suggested that the typical bromid action might be obtained from them, but the action is that of the entire molecule. Both of these have passed almost completely from use as general an- esthetics, largely, perhaps, because of the unstable character of the substances themselves and the ac- companying uncertainty of the action of the de- composition products. Petroleum ether, or benzin, because of its cheapness, is sometimes used in vivisection experi- ments, blit not on man. The use of mixtures of varying composition ap- pears to offer a peculiarly interesting field for ex- perimentation in connection with general anesthe- sia. Of the several mixtures that have been used from time to time, that popularly known as the A. C. E. mixture, containing 1 part of alcohol, 2 parts of chloroform and 3 parts of ether, is per- haps the one that has been used most widely. This, also referred to occasionally as the one-two-three mixture, was, at one time at least, quite popular in England. While it has been urged against this mixture that the differences in volatility of the three substances prevent the anesthetist knowing just what he is administering, it is a fact that the vapors of all three tend to pass off together, and, furthermore, the object is to induce anesthesia and to avoid an excess of the anesthetic and the action of the mixture seems to be as easily controlled as GENERAL ANESTHETICS. 207 that of chloroform, while not so much is required as of ether alone. The alcohol and chloroform raise the boiling point of the mixture above the temperature of the lungs, and this probably secures some of the advantages claimed by Schleich for the mixture of ether, chloroform and benzin. A mixture containing 57 parts of ether and 43 parts of chloroform has been suggested as having some advantages over either of its component parts. It was at one time quite widely recom- mended under the title of M. S. mixture, but ap- pears to have fallen into disuse, having probably no advantage over the better known A. C. E. mix- ture mentioned above. Dr. Carl Ludwig Schleich of Berlin some years ago recommended the admixture of 5 per cent, of petroleum ether, or benzin, with ether and chloro- form, as a general anesthetic. This preparation had been used by Schleich in nearly 500 cases in which he obtained excellent results, such as ab- sence of excitement and of the excessive salivary discharge so frequently seen with ether, while the depressing effect of chloroform on the heart was not observed. Despite these and other advantages, which he cited at the time, the mixture never at- tained much popularity, and even Schleich himself appears to have discontinued its use in favor of an ethyl chlorid mixture. The mixture of ether, chloroform and ethyl chlorid has been proposed at different times and in varying proportions ; the one proposed by Schleich contains 2 parts of ethyl chlorid, 4 parts of chloro- form and 12 parts of ether, and is fairly repre- sentative of this class. The advisability of using mixtures of any kind, 208 PHARMACOPEIA AND PHYSICIAN. for general anesthesia, is still an open question, particularly in view of the fact that the several chemical substances themselves are far from being absolutely stable, even under the most favorable conditions, chloroform particularly being readily decomposed and forming, as one of the possible decomposition products, the really dangerous sub- stance known as phosgene. MAGNESIUM SULPHATE. S. J. Meltzer has recently suggested the use of a solution of magnesium sulphate for inducing general anesthesia. For this purpose he advised the intraspinal injection of 1 c.c. (15 minims) of a 25 per cent, sterilized solution of magnesium sulphate for each 25 pounds of body weight. This method possesses no advantage over cocain used in the same way for producing anesthesia of the lower parts of the body, but general anesthesia is induced and persists for some hours, and the method, there- fore, may possibly prove serviceable in controlling the convulsions of tetanus. Marked depression of the respiration occurs, and Maury and Teague, working with guinea-pigs and injecting the solution intraperitoneally, have found that the repetition of the primary anesthetic dose, on the following day, sometimes causes death. It must, therefore, be used only with extreme cau- tion. The sudden introduction of a small quan- tity of this solution into the blood vessels will im- mediately prove fatal. SCOPOLAMIN-MOKPHIN AND SIMILAR SOLUTIONS. The constant search for less dangerous anesthet- ics than ether and chloroform brings many sub- stances into notice. Morphin and scopolamin have GENERAL ANESTHETICS. 209 found an ardent champion in Korff, who has used them for several years. He employs up to 0.035 gm. (y 2 grain) of morphin and 0.0013 gm. (1/45 grain) of scopolamin. Unconsciousness does not occur, and he claims absolute quiet must be maintained, while he stops operating long enough for pain to subside. He advises “drops” of chloroform or ether when necessary. The tongue must not be permitted to fall back into the throat. Its application in surgery must obviously be very limited. A discussion of a number of fatalities at- tending the use of morphin and scopolamin for general anesthesia will be found in La Semaine Medicale, Hov. 8, 1905, p. 529. Morphin sulphate alone or in combination with atropin sulphate is very commonly employed pre- liminary to chloroform or ether narcosis, and ap- pears to have well established uses in this connec- tion. E. Fraenkel reported some ten years ago that he had habitually used a mixture of morphin, atropin and chloral for hypodermic injections, pre- liminary to narcosis, for twenty-two years, without an accident. He claimed that this procedure les- sened to an extraordinary degree the amount of chloroform or ether used to maintain anesthesia. The solution used by Fraenkel was made as fol- lows : Morphin muriate gr. iiss |15 Atropin sulphate gr. % 015 Hydrated chloral gr- iv 25 Distilled water 3ss 15 1 He injected hypodermically from 1 c.c. to 1.25 c.c. (15 to 19 minims) fifteen minutes before the commencement of the ether or chloroform admin- istration. 210 PHARMACOPEIA AND PHYSICIAN. Fraenkel further asserts that this mixture is free from the objectionable side actions of morphin, being well borne by patients who could not take morphin by the mouth or hypodermically. ETHYL CHLORID. A substance which bids fair to rival chloroform and ether as a general anesthetic, under certain conditions at least, is ethyl chlorid. This substance is extremely volatile, boiling at from 12° to 13° C. (54.5° to 55.4° F.), and it is necessary, therefore, to keep it in sealed tubes. The ends of the tubes are drawn out to fine capil- lary tubes which are then sealed, or the capillary opening is closed by a metal cap which may be re- placed when a part of the contents of the tube has been used. When required for use the glass tip is broken off, or the metal cap unscrewed, when the heat of the hand causes the ethyl chlorid to vola- tilize, forcing out a fine stream which may be di- rected against the surface which is to be frozen for local anesthesia, or the stream may supply the vapor for inhalation to produce general anesthesia. Ethyl chlorid induces anesthesia more rapidly than ether does, and when it is withdrawn the pa- tient recovers more quickly, thus saving an average of some twelve minutes on each operation, hence it is likely to prove useful on the battlefield and in great calamities when a number of operations must be performed with a minimum loss of time. Figures purporting to give relative degrees of danger for various anesthetics are notoriously un- reliable, but it seems probable that ethyl chlorid is less dangerous than chloroform and somewhat more dangerous than ether. Among the objec- GENERAL ANESTHETICS. 211 tionable features of ethyl chlorid are increased cost, the explosive character of the vapor, extreme volatility, the accompanying waste of material and the difficulty of administration. ACTION OF CHLOROFORM AND ETHER. It would hardly be profitable to discuss here in detail the actions of chloroform and ether, but there are certain important points concerning them which are so frequently overlooked that we will consider them briefly. While there are records of as many as 40,000 consecutive anesthetizations with chloroform with- out a fatality, this is only possible in case of skilled anesthetists working with carefully selected cases. Certainly no such results are possible in ordinary practice, and with that alone we are concerned at present. We must always remember that the production of general anesthesia is a grave matter, in which death is an ever present possibility despite the ut- most care, and of which there is actual danger un- less caution is observed. The possibility of fatal complications in all cases of general anesthesia would appear to make it necessary that the patient or his friends be informed of this fact, if for no other reason than to protect the physician admin- istering the anesthetic. Each case must be carefully considered when se- lecting the anesthetic, and neither chloroform nor ether should be used exclusively. Ether being the safer, however, should have the preference, when it is not contraindicted, and chloroform should not be used unless the anesthetist is experienced and is reasonably skilled in the use of it. The following are some of the principal advan- 212 PHARMACOPEIA AND PHYSICIAN. tages and contraindictions of both of these agents : The vapor of ether is inflammable, that of chlor- oform is not, and the latter is to be preferred when operations are to be performed by gas or lamp- light. In this connection, however, we must not forget that chloroform vapor coming in contact with an open flame is readily decomposed into chlorin and hydrochloric acid, and that it will be necessary, therefore, to provide for free ventila- tion to eliminate these decomposition products. If ether must be used under such circumstances, the light- should be placed as high above the level of the mask as practicable, since ether vapor is heavier than air. The thermocautery can, of course, also ignite the vapor of ether. An acute cold is a contraindiction to the use of any anesthetic, but more particularly to the use of ether. Ether is also contraindieted in bronchitis, because of the great irritation caused by the rela- tively large amount necessary to maintain anes- thesia; it is likewise contraindicated in nephritis, since the kidneys take part in the excretion, and suffer from the irritant action. In extremely hot weather, that is, when the ther- mometer is above 93° to 95° F. (34° to 35° C.), ether is volatilized so rapidly that the atmosphere contains amounts which may prove objectionable, and it often becomes very difficult to maintain com- plete anesthesia. When it is absolutely imperative to reduce the stage of excitement to the minimum, or when it becomes necessary to secure complete anesthesia rapidly, ether is contraindicated and chloroform is to be preferred when it is not specifically contra- indicted for other and more important reasons. In GENERAL ANESTHETICS. 213 the latter event ethyl chlorid may be used, or pre- liminary unconsciousness may be induced by ni- trous oxid, and this followed up by the use of ether. Chloroform is very commonly preferred by ob- stetricians, but deep anesthesia is not usually in- duced in such cases. In fatty disease of the heart chloroform is con- traindicated because it also induces fatty degenera- tion of that organ, and for this reason it is not ad- visable to use it repeatedly on the same person in succeeding operations. Chloroform is much more toxic to the heart than ether, and there is a much narrower margin for safety between the amount necessary to induce an- esthesia and that which causes death, chloroform being thirty-six times as active as ether in induc- ing anesthesia, but forty-eight times as toxic. A matter of the greatest importance, especially for the unskilled anesthetist, is the very brief in- terval between the cessation of respiration and the- stopping of the heart beat with chloroform, giving; very little chance to resuscitate the patient after respiration has stopped. With ether the interval is much longer, and the prompt resort to artificial respiration, while the body is raised higher than the head, very commonly results in saving the pa- tient. This difference in the action of anesthetics and also the fact that the condition of anesthesia is a dangerous one, according to the degree to which it is carried, will be more fully appreciated if we have a clear conception of the several stages of an- esthesia and the rapidity with which a patient may pass from one stage into the other. These several stages are usually designated as: 214 PHARMACOPEIA AND PHYSICIAN. 1 , the stage of excitement; 2, the narcotic and anodyne stage ; 3, complete anesthesia ; 4, paraly- sis and death. The acceleration of the circulation noticed in the first stage is similar to that produced by the inges- tion of alcohol or alcoholic beverages, and the pro- duction of this stage was one of the uses to which ether was put long before it was used as an anes- thetic in surgical operations. From this stage the patient usually passes quite gradually into the second or narcotic stage. In the narcotic stage sensibility becomes im paired, but there is not infrequently a persistence of reflex action which manifests itself in a form of delirium or wild excitement. This is usually an indication of faulty anesthetization and is a com- plication that can be avoided in many instances by the more careful preparation of the patient for the anesthetic. In the majority of instances, however, the patient passes rapidly into the third stage, that of complete anesthesia. This difference in the action of anesthetics and there is complete absence of reflex action, even of the conjunctiva, which is usually, though erron- eously, advocated as the most satisfactory test for complete anesthesia. A satisfactory surgical anes- thesia is indicated by complete relaxation of nearly all of the muscles , of the body, regular breathing, deep inspirations and a fully relaxed lower jaw. The widely prevailing though barbarous habit of touching the conjunctiva should never be re- sorted to. By the careful administration of the anesthetic this stage of surgical anesthesia may be continued for a considerable period of time, but we must GENERAL ANESTHETICS. 215 never forget that it is ever bordering on, and may at any moment pass into, the fourth or paralytic stage, when respiration ceases, the heart heats be- come feebler, and, unless vigorous and prompt restorative measures can be resorted to, may cease entirely. THE ADMINISTRATION OF ETHER. While it has been asserted that the administra- tion of anesthetics is an art that can not be taught or learned, but must be acquired, it is also true that there are certain points or rules that have been sufficiently well established to warrant their being heeded, and the general conduct of anesthetization can best be illustrated, perhaps, by giving the method pursued by an ordinarily careful anes- thetist. The patient is made thoroughly comfortable, in a recumbent position, on a table or wheel stretcher, if in a hospital, with a pillow just sufficient to raise his head but slightly. The mouth is freed from false teeth and other foreign materials, and the lips and nose are an- ointed with petrolatum to avoid the accompanying irritation from contact with the anesthetic. A pad of moistened gauze is then placed over the eyes to avoid irritation by the fumes of the anes- thetic. All these several stages should be carefully ex- plained to the patient so as to assure him that every possible precaution is being taken to provide for his comfort and well-being, and to gain his confidence, for the more important feature of ad- ministering the anesthetic itself. After the patient has been prepared and his con- fidence gained by explanation of the several stages 216 PHARMACOPEIA AND PHYSICIAN. of the preparation, he is allowed to accustom him- self somewhat gradually to the taste and smell of ether. To accomplish this the cone or gauze con- taining the anesthetic is held some slight distance from his face, and gradually brought closer as the patient becomes more and more accustomed to the inhalation. If the anesthetist has been successful in gaining the confidence of the patient he will find that the latter will pass through the prelim- inary stages of anesthesia without a struggle, and that complete relaxation will be secured with a minimum of the anesthetic. When a patient has been completely anesthetized very little of the anesthetic will suffice to maintain the condition and the. further efforts of the anes- thetist can be devoted to observing the respiration and the surface reflexes of the patient in order to prevent his reverting to the second stage of anes- thesia, or passing on into the much-to-be-dreaded stage of paralysis of the respiratory center. With chloroform the passing from one stage of anesthesia to the next is much more rapid than with ether, less of the anesthetic is used, more air must be allowed, and there is, of course, a cor- respondingly smaller margin of safety in the stage of complete surgical anesthesia. Since all of us can not become expert anesthet- ists and yet must at times perform that office, this advantage of ether is well worth consideration. The greatest immediate danger from inhalation of ether or chloroform, but more especially of the latter, is the administration of the vapor in too great concentration. One hundred volumes of air require approximately from three to four volumes of ether vapor, and 100 volumes of air require GENERAL ANESTHETICS. 217 about one volume of the vapor of chloroform to in- duce anesthesia, but an increase of from two to three volumes in the concentration of the ether, or of only one volume of chloroform in 200 of air will prove fatal in a short time. While we do not actually measure the relative volumes of air and vapor, as a rule, these figures will serve to show the comparative danger of the two substances, for it' is many times more difficult to avoid overstepping narrow boundaries than broad ones. When a perfectly safe ratio is maintained the delay in inducing anesthesia often proves vexa- tious, and the anesthetist may be urged to expedite the operation by increasing the concentration, but he should never -forget the grave responsibility which he has assumed and should never permit the impatience of others to induce him to exceed the limits of caution, save only in those grave emer- gencies where delay in operating may mean death to others who are awaiting their turn. OFFICIAL ANESTHETICS. JEthylis Chloriduh. — U. S. — Ethyl chlorid occurs as a colorless, transparent, very volatile liquid, having a characteristic, rather agreeable odor and a burning taste. It is only slightly sol- uble in water, but is readily miscible with alcohol. Ethyl chlorid is a haloid derivative, and is pre- pared by the action of hydrochloric acid gas on ab- solute ethyl alcohol. It is usually marketed in hermetically sealed glass tubes, and when liberated at ordinary room temperature volatilizes almost in- stantly. The resulting gas is very inflammable 218 PHARMACOPEIA AND PHYSICIAN. and the substance itself should never be used in proximity to an open flame or fire. For local anesthesia the liquid in a fine spray is applied to the surface to be anesthetized. The average amount necessary to induce general anesthesia is from 5 to 10 c.c. (75 to 150 minims). FEther. — U. S. — Ether is a transparent, color- less, volatile liquid having a characteristic odor and a pungent, sweetish taste. It should contain 96 per cent, by weight of absolute ether or ethyl oxid and about 4 per cent, of alcohol containing a little water. The per cent, content of ethyl oxid or absolute ether in a given specimen is a matter of consider- able importance when the substance is to be used for anesthesia. The official ether, when exposed to air, absorbs moisture, thus materially re- ducing the anesthetic value of the ether. The practice that has long been followed of sending out ether in hermetically sealed cans is an efficient safeguard against this absorption of moisture. Chloroeormum. — U. S. — Chloroform is a heavy, clear, colorless liquid having a characteristic ethereal odor and a burning, sweet taste. It should contain not less than 99 per cent, by weight of ab- solute chloroform and from 0.6 to 1 per cent, by weight of alcohol. Chloroform when not pure is readily decom- posed, forming chlorin compounds that may prove to be extremely dangerous to the patient. Even chloroform that corresponds to the requirements of the Pharmacopeia may be decomposed in the presence of damp air and heat, and the substance should, therefore, be carefully preserved in small, well-stoppered bottles. CHAPTER IX. EXPECTORANTS. The prevalence of coughs and “colds” in the winter months is sufficient evidence of the import- ance of this class of agents. Their use in domestic practice — largely as “patent medicines,” so-called — probably exceeds that directed by the physician as ten to one. Physicians are supplied liberally with literature by manufacturers of proprietary remedies of this type, but the pharmacology of this literature is not always worthy of the faith that some physicians place in it. As an example we quote from a circu- lar distributed exclusively to physicians: “In se- vere and frequent cough, when little mucus is se- creted, as shown by the scanty viscal sputum, mor- phin, or, better, its derivative, ethyl-morphin, is indicated, which increases secretion and lowers ex- citability of the respiratory center.” For compari- son with this interested statement by the manufac- turers we quote from the article on opium in Wood’s Therapeutics (11th ed., 716) : “Its ten- dency to cheek secretion forbids its use, however, in a very large proportion of cases, notably in those in which there is persistent dryness of the bronchial mucous membrane.” Sollmann, Cushny and oth- ers state that morphin possesses the same property, though to a lesser degree than opium. In their proprietary medicine circular manufac- turers usually advocate the use of some certain 220 PHARMACOPEIA AND PHYSICIAN. remedy for all coughs, but we may be pardoned if we again quote W ood for comparison : “It is plain that the medical practitioner must study in each individual case the relations between the cough .and the amount of work required/’ The discovery of a medicinal agent is the signal for a host of imitators whose product may differ, if at all, merely in the substitution of an ethyl for a methyl group, or of one harmless acid radical for another. These are presented in increasing num- bers to the physician, who can by no possibility remember them all. Or, some well-known drug, whose length of service, if not merit, entitles it to some respect, is seized on to serve as a basis for fabulous claims, perhaps long since voiced, dis- proved and forgotten. There is still another interesting phase con- nected with these various nostrums. Many of us pride ourselves on the fact that we use only “eth- ical” preparations and also that we insist on know- ing just what we are prescribing or using. It must be rather embarrassing, therefore, to find that even the public is more exacting in this respect than we are and that the manufacturers of popular medicines, when they do advertise the composition of their particular mixture, publish a full and complete formula and not an incomplete one such as we frequently find in the advertising pages of medical journals, or in the circulars that come to our desk. The expectorants official in the United States Pharmacopeia afford a great variety of choice. In- numerable combinations are possible, but we shall merely suggest a few of these, in connection with some of the drugs and preparations available. EXPECTORANTS. 221 It should be remembered that coughing serves to remove mucus from the respiratory tract and usually requires no treatment. If, however, the cough becomes unduly severe, it may require alle- viation; if the secretion is scanty it may be in- creased or rendered more liquid. Acute bronchitis may be divided into two gen- eral stages, with certain expectorants useful in each stage, but this is not to be taken as a rigid classification. The first stage — that of dryness of the mucous membrane, with considerable cough — calls for sed- atives ; the second — that of free secretion — re- quires stimulant expectorants. SEDATIVE EXPECTORANTS. Among the official sedative expectorants to be used in the first, or dry, stage of cough, we have the following: Ipecacuanha. — U. S. — Ipecac is the dried root of Cephaelis Ipecacuanha (Brotero), A. Bichard (Fam. Rubiacece) . It is known commercially as Bio, Brazilian or Para ipecac, or the corresponding portion of C. acuminata , Ivarsten, known commer- cially as Carthagena ipecac, yielding, when assayed by the process given in the Pharmacopeia, not less than 2 per cent, of ipecac alkaloids. Ipecacuanha was first described by Piso and Markgraf, in 1648, in their natural history of Brazil. The drug ap- pears to have been well known to the natives of Brazil and to have been much prized for a variety of therapeutic purposes. It was introduced into Europe, about 1675, by John Helvetius, of Paris. The Carthagena variety of ipecacuanha is a com- 222 PHARMACOPEIA AND PHYSICIAN. paratively recent introduction, being first noted as a distinct variety, about 1870. Ipecacuanha is of- ficial in all pharmacopeias, but up to the present time the Pharmacopeia of the United States is the only one to recognize the Carthagena variety as being the equal of the Brazilian. Pul vis Ipecacuanha. — U. S. — Average dose: Expectorant, 0.050 gm. (1 grain) ; emetic, 1 gm. (15 grains). Fluidextractum Ipecacuanha. — U. S. ; — Fuidextract of Ipecac.— This should contain 1.75 per cent, of alkaloids. Average Dose: Emetic, 1 c.c. (15 minims); expectorant, 0.05 c.c. (1 minim). Pulyis Ipecacuanha et Opii. — U. S. — Pow- der of Ipecac and Opium (Dover’s powder). This contains 10 per cent, of ipecac, 10 per cent, of pow- dered opium and 80 per cent, of sugar of milk. Average Dose: 0.500 gm. (7% grains); used chiefly as a diaphoretic. Syrupus Ipecacuanha. — U. S. — Svrup of Ipe- cac. This contains 7 per cent, of fluidextract of ipecac and 1 per cent, of acetic acid in a mixture of glycerin, sugar and water. Average Dose: Expectorant, 1 c.c. (15 min- imus) ; emetic, 15 c.c. (4 fluidrachms). Vinum Ipecacuanha. — U. S. — Wine of Ipe- cac. A mixture of 10 per cent, of fluidextract of ipecac, 10 per cent, of alcohol and 80 per cent, of white wine. Average Dose: 1 c.c. (15 minims). When the bronchi are inflamed and the secretion is scanty or thick and tenacious, nauseants, such EXPECTORANTS. 223 as ipecac, lead to increased secretion which secures its removal by coughing. The choice of nau- seants is guided by the general condition of the patient, ipecac being preferred to antimony and potassium tartrate in those eases (children and weakly persons) in which great depression would be dangerous. The active principle of ipecac is not usually employed in the pure state as an ex- pectorant, the syrup of ipecac being preferred, as the tannin present retards absorption and prolongs the action. The expectorant dose of nauseants is always very much less than the emetic— approximately one- tenth in the case of ipecac. The average doses given are approximate and the expectorant dose is to be repeated every two or three hours ; the emetic dose is to be repeated half-hourly until effective. For croup in small children few remedies enjoy a greater reputation than syrup of ipecac, which is given alone in doses of from ten to thirty drops, repeated at intervals of thirty minutes until vom- iting occurs. The preparations of ipecac are seldom used alone as expectorants, but are usually added to mixtures of allied use. The following may be considered a typical pre- scription for ipecac to be used in teaspoonful doses every two hours; for the syrup of ipecac a corre- sponding amount of fluidextract or wine may be substituted. When an opiate is imperatively de- manded 15 c.c. (4 drachms) of camphorated tinc- ture of opium may be added without other change : R. Syrupi ipecacuanh® 3vi 25 1 Ammonii chloridi 3iss 6| Syrupi tolutani, q. s. ad §iii 100 1 224 PHARMACOPEIA AND PHYSICIAN. Senega. — U. S. — Boot of Polygala Senega — This is one of the few drugs of American origin that has found a place in every recent pharmaco- peia. It contains a saponin which is locally irri- tant, but which is not absorbed ; hence, the drug is not depressing. It is almost invariably used in small amount as an addition to other expectorants. It has the disadvantage of an unpleasant acrid taste. The official preparations are: Fluidextracttjm Senegje. — U. S. — Average dose, 1 c.c. (15 minims), and Syrupus Senega. — U. S. — This contains 20 c.c. fiuidextract of senega in 100 c.c. Average Dose: 4 c.c. (1 fluidrachm). See also compound syrup of squill. Another irritant nauseant more notable for its abuse than use is : Sanguinaria. — U. S. — Rhizome of Sanguinaria canadensis (bloodroot). This drug, usually omit- ted by modern therapeutists or dismissed with a line, contains sanguinarin, belonging to the mor- phin group, and causing depression of the respira- tory center. It is mentioned here more particu- larly because of its widespread use by the nostrum makers. The common name — bloodroot — appears to possess considerable psychical effect. The In- dians, probably, displayed more wisdom in its use than we do ; they only applied it externally, as war paint. The only official preparation is : Fluidextractum Sanguinaria. — II. S. Average Dose: 0.1 c.c. (1% minims). The “Compound Syrup of White Pine' - ’ of the National Formulary represents the “popular” ex- EXPECTORANTS. 225 pectorant. It is not recommended, however, as it is too complicated. 1 ANTIMONY. Antimony and potassium tartrate is a more depressing nauseant than the drugs above men- tioned. It may be used on robust persons, but not with safety on children or the infirm. Its mode of action is similar to that of ipecac, and here, too, we have a variety of official preparations. Antimonii et Potassii Tartras. — U. S. — Antimony and Potassium Tartrate; tartar-emetic. Colorless, transparent crystals or a white, granu- lar powder, soluble in 15.5 parts of water. This is the most popular and widely used of the medicinal compounds of antimony, and is now official in all recent pharmacopeias. Average Dose: Expectorant, 0.005 gm. (1/10 grain) ; emetic, 0.03 gm. (% grain). Yinum Antimonii. — TJ. S. — Wine of Antimony. This contains 0.4 per cent, of antimony and potas- sium tartrate in solution in 1 part of alcohol and 5 parts of white wine, and enters the well-known compound mixture of glycyrrhiza — a deservedly popular expectorant. Average Dose: Of the wine 1 c.e. (15 minims). 1. The following is the formula for the Compound Syrup of White Pine : White pine hark (pinus strobusi . . . . Jiiss 75 1 Wild cherry bark oiiss 75 Spikenard root 3iiss 10 Balm of Gilead buds 3iiss 10 Sanguinaria root 3ii 8 Sassafras bark .’ grs. cv 7 Morphin sulphate grs. viiss 5 Chloroform 3iss 6 Sugar Sxsvss 750 Alcohol Water Syrup (TJ. S.), of each to make Oil 1000 226 PHARMACOPEIA AND PHYSICIAN. Tartar emetic is also an ingredient (0.2 per cent.) in the compound syrup of squill. For the administration of antimony and potas- sium tartrate, the official compound mixture of glycyrrhiza (6 per cent, wine of antimony, 0.024 per cent, antimony and potassium tartrate) is used alone or with 4 gm. (60 grains) ammo- nium chlorid to 60 c.c. (2 ounces). A typical prescription containing wine of anti- mony follows: R. Vini antimonii 3iv 15 1 Aquae chloroformi, q. s. ad 3hi 100 1 A teaspoonful every two hours. Apomorphina: Hydrochloridum. — U. S. — Apomorphin Hydrochlorid. — The hydrochlorid of an alkaloid prepared from morphin by the abstrac- tion of one molecule of water. It is soluble in 40 parts of water, in the same proportion of alcohol, practically insoluble in all other solvents. Apomorphin is much less useful as an expector- ant than as an emetic, its action being brief. Average Dose: Expectorant, 0.002 gm. (2 mg. or 1/30 grain) ; emetic, 0.005 gm. (5 mg. or 1/12 grain). Ammonii Chloridum. — U. S. — A white cryst- alline powder, without odor, having a cooling sa- line taste, permanent in air, soluble in 2 parts of water and in 50 parts of alcohol. As sal ammoniac, this substance has been known from a very early time. It is popularly supposed to have been first obtained from the neighborhood of the Temple of Jupiter Ammon, in Northern Africa. Ammonium chlorid was known to the Arabian physicians and was described by Geber. It is now EXPECTORANTS. 227 official in all pharmacopeias. Wood recom- mends this salt in the stage just before secretion becomes free ; for this purpose the following may be used: Trochisci Ammonii Chloridi. — U. S. — Bach troche contains 0.1 gm. (IV 2 grains) ammonium chlorid and 0.2 gm. (3 grains) extract of glycyr- rhiza. Ammonium chlorid is much used as an addition to compound mixture of glycyrrhiza in the propor- tion of 4 gms. (60 grains) to 60 c.c. (2 ounces), and it may be added to nearly any expectorant mixture which is not strongly alcoholic. STIMULATING EXPECTORANTS. Balsamum Tolutanum. — U. S. — Balsam of Tolu is a balsam obtained from Toluifera bal- samum, a yellowish-brown plastic solid that has a pleasant aromatic color and a mild aromatic taste. It is readily soluble in alcohol, nearly insoluble in water. Balsam of tolu was first described by Monardes, a Spanish physician, about 1574. The drug, it is said, was collected in a district called Tolu, near Carthagena, and appears to have been well known to, and used by, the natives of Northern South America. Balsam of tolu, at the present time, is a widely used and popular drug and is official in all the leading pharmacopeias. Average Dose: 1 gm. (15 grains). Syrupus Tolutanus. — U. S. — Syrup of Tolu, containing the water-soluble principles of 5 per cent, of tincture of tolu in syrup. Average Dose: 15 c.c. (4 fluidrachms) . Tinctura Tolutan^:.— U. S. — Tincture of Tolu, a 20 per cent, solution of tolu in alcohol. 228 PHARMACOPEIA AND PHYSICIAN. Average Dose: 2 c.c. (30 minims). The mildest of the stimulant expectorants is syrup of tolu, if, indeed, this can be considered as anything more than a flavored syrup. The balsam is not frequently used in medicine, but may be given in the form of an emulsion made with acacia and water and. sweetened with sugar. The benzoic acid and volatile oil in the balsam give it the advantage of being mildly antiseptic, the syrup, however, being too weak to be effective in the dose usually employed. Balsamum Peruvianum. — U. S. — Balsam of Peru may be used in the same dose and for the same purpose as balsam of tolu. Attention is called to the fact that the urine of persons taking such amounts of these balsams gives a precipitate with nitric acid which may be mis- taken for albumin, but the precipitated resins dis- solve in alcohol, while albumin does not. Benzoinum. — U. S. — This balsamic resin is also a harmless stimulant, useful in bronchial irrita- tion. Tinctura Benzoini. — U. S. — A 20 per cent, solution of benzoin in alcohol, or : Tinctura Benzoini Composita. — IT. S. — “Turlington’s balsam,” commonly called “Friar’s balsam” (containing benzoin, aloes, storax and tolu), may also be given. Average Dose : 1 c.c. (15 minims) every two hours. The fact that these expectorants are harmless is a very great advantage — and is a point to be par- ticularly remembered in the treatment of small children, in whom opiates and such depressants as antimony and potassium tartrate are to be avoided. EXPECTORANTS. 229 Syrupus Picis Liquids. — U. S. — Syrup of Tar. — Containing one-half of one per cent, of the soluble principles of tar in syrup, is mildly stimu- lant and the taste is not unpleasant. Average Dose: 4 c.c. (1 fluidrachm). Tar itself has a disagreeable acid taste and is not often used in substance. Tprpini Hydras. — U. S. — Terpin Hydrate. — This is a body closely related to turpentine, camphor, etc. It occurs in colorless, lustrous, rhombic prisms, or a white crystalline powder, nearly odorless, of a slightly aromatic and some- what bitter taste, soluble in about 200 parts of water and in 10 parts of alcohol. Average Dose: 0.1 gm. (2 grains) in capsules or elixir. Owing to its slight solubility in water, the elixir must be strongly alcoholic and glycerin be substituted for syrup — a serious objection to its general use. It is very commonly associated with codein, which is not to be recommended for rou- tine practice. It may be prescribed as the unofficial Elixir of Terpin Hydrate and Coclein Sulphate. Dose : Two teaspoonfuls, containing 0.15 gm. (2 grains) ter- hydrate and 0.024 gm. (14 grain) codein. Terpin hydrate has been known for some time, but was not used in medicine until after Lepine published the results of his physiologic investiga- tion in 1885. It is supposed to possess the anti- septic and stimulating effects of turpentine with- out possessing its irritating properties. The sub- stance soon became popular and was included in the United States Pharmacopeia for 1880. It is official in the German Pharmacopeia and in the French Codex. 230 PHARMACOPEIA AND PHYSICIAN. Terpin hydrate has been suggested as a remedy in a variety of ailments, but it appears to be useful mainly as an expectorant, enjoying a reputation particularly among the nostrum venders. It is in reality, useful in aiding to get rid of secretion from the bronchial mucous membrane. Tekebenum. — U. S. — Terebene. — This is a polymerization product derived from turpentine, which it closely resembles. It is a colorless liquid, having a rather agreeable odor and an aromatic, somewhat terebinthinate taste, readily soluble in 3 times its volume of alco- hol, but only slightly soluble in water. First obtained by Soubeiran and Capitaine about 1841, it was introduced into medicine by Dr. William Murrell about 1885; it was made official in 1890 and in the British Pharmacopeia of 1898. It is used in much the same conditions as terpin hydrate ; its immiscibilitv with the mixtures usu- ally employed as expectorants has interfered in no small way with its employment. It may be pre- scribed in alcoholic solution, in capsules or in the form of an emulsion. Average Dose: 0.5 c.c. (8 minims). Scilla. — U. S. — Squill. The bulb of Urginea maritima, containing several potent principles, it is exceedingly irritant and in large doses toxic. Average Dose: 0.1 gm. (2 grains). Of all official drugs used in the treatment of cough, few are better known than squill, the syrup being the most popular of its preparations. This drug is both stimulant and nauseant ; hence, it is used in both stages of bronchitis. Syrupus Scilla. — U. S. — Syrup of Squill. This represents 5 per cent, of squill ; made from EXPECTORANTS. 231 vinegar of squill, and, therefore, containing dilute acetic acid; it is, of course, incompatible with am- monium, and other, carbonates — a fact not infre- quently lost sight of by the prescriber. Acetum Scillje. — JJ. S. — Vinegar of Squill. This represents 10 per cent, of the drug extracted with dilute acetic acid. Average Dose: 1 c.c. (15 minims). Fluidextractum SciLLiE. — U. S. — Average Dose, 0.1 c.c. (2 minims). Tinctura SciLLiE. — U. S. — This represents 10 per cent, of the drug. Average Dose: 1 c.c (15 minims). These last three preparations of squill are sel- dom employed, but the following is widely used : Syrupus Scill.e Compositus. — U. S. — Com- pound Syrup of Squill (Hive Syrup). This repre- sents 8 per cent, of the fluidextracts of squill and senega and 0.2 per cent, of antimony and potas- sium tartrate or about 0.01 gm. (% grain) to the teaspoonful. Average Dose: 2 c.c. (30 minims). The use of squill as an emetic is not free from danger and the drug is seldom so employed alone. Creosotum. — U. S.— (or Guaiacol. — TJ. S., which constitutes up to 90 per cent, of creosote) is used as a stimulant expectorant. There is con- siderable diversity of opinion as to its mode of ac- tion. It seems to possess little germicidal action so far as the lungs are concerned. When it is ad- ministered in a bland oil very large doses are tol- erated, but these are not necessary for its expector- ant effect. Numerous compounds of creosote and of guai- acol have been suggested as substitutes for the ofB- 232 PHARMACOPEIA AM) PHYSICIAN. cial products, but it is not probable that they pos- sess any decided advantages over the official. Those which are less poisonous are probably ab- sorbed from the alimentary canal to a much less degree than are the official creosote and guaiacol. Among the guaiacol compounds is the proprie- tary “Ethacol,” containing ethyl-morphin, a fact to be carefully borne in mind, as the name of the preparation is not nearly so suggestive of morphin as of guaiacol. The manufacturers of this article recommended morphin or ethyl-morphin in bron- chitis for increasing secretion ! ANODYNES. When the irritability of the throat causes excessive coughing, anodynes are indicated. Morphin, how- ever, must only be used with the greatest caution owing to its tendency to check secretion, “free cir- cular therapy” to the contrary notwithstanding. Codeina. — IT. S. — Codein. Very soluble in al- cohol, much less soluble in water. CODEINiE PlIOSPHAS. — U. S. Codeine Sulphas. — IT. S. — Both are quite sol- uble in water, but not in alcohol. Average Dose: 0.003 gm. (3 mg. or 1/20 grain). Codein, rather than its salts, is suited for com- bination with terpin hydrate, since both require al- cohol as solvent. Codein has come very largely into use in expec- torant mixtures in recent years, partly because its action resembles that of morphin without disturb- ing digestion or causing constipation in moderate doses, partly, no doubt, because manufacturers have popularized it in order to avoid the stigma attaching to the general use of morphin and opium. EXPECTORANTS. 233 Coclein undoubtedly lessens cough, but, as al- ready stated, this is not always desirable. Codein phosphate or sulphate, being soluble in water, may be added to almost any cough mixture which is not alkaline. The following is suggested as a simple prescrip- tion containing codein : R. Codeina- sulph grs. viii |5 Ammonii chloridi 3iss 6| Syrupi pruni virg. q. s. ad §iii 100| M. Sig. : A teaspoonful every two or three hours. Compound mixture of glyeyrrhiza, syrup of tar, syrup of squill or syrup of tolu may be substituted wholly or in part, for the syrup of wild cherry. Ammonium chlorid is not well suited for com- bination with terpin hydrate, since the latter re- quires a strongly alcoholic menstruum which pre- cipitates ammonium chlorid. Numerous substitutes have been introduced for morphin and codein, but it has not been demon- strated that they possess all the advantages and none of the disadvantages of the officials. It must not be forgotten that the habit may be formed with any of the morphin derivatives, including codein. The bromids of ammonium, potassium and so- dium are safer than morphin, and are frequently beneficial when anodynes are indicated. Their doses should, however, be more than proportion- ately reduced for children. Hydrocyanic acid may be added to expectorant mixtures, but its action is fleeting and it must be frequently repeated. Acidum Hydrocyanicum Diltttum. — TJ. S. — Contains 2 per cent, absolute HCN. 234 PHARMACOPEIA AND PHYSICIAN. The average dose is 0.1 c.c. (l 1 /^ minims). DEMULCENT EXPECTORANTS. Demulcents are frequently employed to allay the irritation of the mucous membrane, and they pos- sess the great advantage of being harmless. They may be administered in the form of lozenges or troches. The following demulcents may be used as ve- hicles : Syrupus ACACIiE. — U. S. Mucil ago Acacije. — U. S. Glycyrrhiza. — U. S.- — Licorice Boot is so well known as to require but little comment. Its prep- arations afford a variety of forms for administer- ing it. Fluidextractum Glycyrrhiza. — U. S. — This is the Fluidextract of Licorice Boot, from which a satisfactory syrup may be prepared by mixing 25 c.c. of the fluidextract with enough syrup to make 100 c.c. Average Dose: 2 c.c. (30 minims). Extractum Glycyrrhiza Purum. — U. S. — This is a semi-solid extract prepared from the root and is well adapted as an addition to extempora- neous mixtures. Average Dose: 1 gm. (15 grains). TrOCHISCI GLYCYRRHIZA ET OpII. — U. S. — These contain 0.005 gm. (5 mg. or 1/12 grain) of opium. Glycyrritizinum Ammoniatum. — U. S. — Am- moniated Glycvrrhizin is an excellent demulcent; it is readily soluble in water, but incompatible with acids. Average Dose: About 0.25 gm. (4 grains). EXPECTORANTS. 235 PULVJS GLYCYRRHIZA COMPOSITUS. — U. S. — Compound Powder of Glycyrrhiza, a laxative, con- taining senna, washed sulphur, glycyrrhiza, sugar and oil of fennel, and is popularly believed to be a desirable adjuvant to expectorant medicines. Average Dose: 4 gm. (60 grains). Mistura Glycyrrhiza Composita. — Com- pound Mixture of Glycyrrhiza, brown mixture, con- taining purified extract of glycyrrhiza and acacia, each 3 per cent., syrup 5 per cent., with camphor- ated tincture of opium 12 per cent., wine of an- timony 6 per cent, and spirit of nitrous ether 3 per cent. Average Dose: 8 e.c. (2 fluidrachms) . This is a deservedly popular expectorant. It is very often prescribed alone, but is also much used as a vehicle for other expectorants, particularly ammonium chlorid. Ammonii Carbonas. — U. S. — Ammonium Car- bonate. This consists of white, hard, translucent, striated masses of a strong odor of ammonia with- out empyreuma, and a sharp, saline taste, slowly but completely soluble in about 4 parts of water and decomposed by hot water. A condition deserving especial mention is that in which the mucus is particularly thick and te- nacious, requiring liquefaction ; for this purpose, ammonium carbonate is frequently added to other expectorants; it has the disadvantage of an un- pleasant taste, which can not be disguised with di- luted acids because these decompose the carbon- ates. The cough of chronic bronchitis requires the use of one of the stimulant expectorants, such as terebene or terpin hydrate, bearing in mind the 236 PHARMACOPEIA AND PHYSICIAN. avoidance of those which will prove objectionable with continued use. While urging the advantage of using the phar- macopeial expectorants, we particularly suggest that the physician consider the several ingredients of any nostrum instead of accepting the absurd and often grotesque claims of the manufacturer. CHAPTER X. ANALGESICS AND SOPORIFICS. Analgesics and soporifics are among the most important articles in the materia medica, and at the same time, owing to their abuse, among the most harmful. Pain, accompanied by sleeplessness, occurs in a great variety of conditions, often with an inten- sity or persistency that imperatively demands alle- viation. When such a condition requires medi- cines for a long time there is danger that the pa- tient will learn the name of the remedy employed and continue its use after the actual necessity for it has passed. Certainly no other class of reme- dies requires more painstaking care on the part of the physician, not only in the choice of the par- ticular agent to be used, but also in the regulation of the dose. The way to secure the best results in the treat- ment of such conditions is by acquiring an inti- mate knowledge of the ~ various remedies in this class and by learning how to use them singly or in combination as may be required. In a given case a combination of hyrated chloral and potassium bromid may be necessary, while in another the latter alone may suffice. The more dangerous hydrated chloral should never be used when the less harmful bromid will serve the pur- pose . 1 1. Should the physician desire to use a compound mixture of hydrated chloral and potassium bromid of the bromidia 238 PHARMACOPEIA AND PHYSICIAN. If we find that scarcely any two successive pa- tients demand exactly the same prescription of but two ingredients, how very much less is the proba- bility of finding any considerable number each re- quiring a “shotgun” prescription of five or six substances of widely different action, agreeing only in the one property of producing unconscious- ness. It should be obvious that the conscientious use of analgesics and soporifics demands the thought- ful selection of the remedy with the careful com- putation of the dose according to the necessities of the individual case — a condition manifestly im- possible when one relies on complex, ready-made mixtures, with doses and indications suggested by an interested layman — the manufacturer. The greater the number of individuals who acquire such harmful habits the greater are the profits of the nostrum maker. It is well known that the habitual use of opium, hydrated chloral, the bromids and other narcotics type he may have the “Mistura Chloralis et Potassii Bromidi Composita” of the National Formulary compounded, as fol- lows : R. Chlorali hydratis Potassii bromidi, aa 3i-gr. xv Ext. eannab. ind. Ext. hyoscyami, aa gr. % 04 Aquas q. s. ad 3vi The hydrated chloral and the potassium bromid are dis- solved in a little water and the extracts are then dissolved in the solution of the salts mixed with some powdered pumice stone, and the mixture filtered. Each teaspoonful will contain approximately 1 gm. (15 grains) each of hydrated chloral and potassium bromid ; 0.008 gm. (Vs gr.) each of extract of Indian cannabis and extract of hyoscyamus. The mixture should be used with caution, and it will usually be found advantageous to omit the extract of Indian cannabis. This mixture is unscientific in the extreme and we do not commend its use. ANALGESICS AND SOPORIFICS. 239 is widespread, but there are few who appreciate the full extent of these practices, or in how far physicians are responsible because of the careless use of these agents, either in simple form or as an ingredient of some nostrum. For more convenient consideration we shall di- vide these remedies into the opium, atropin, ace- tanilid, hyrated chloral and bromid groups, the first three being more properly analgesics and the last two soporifics, though no absolute distinction can be drawn between them. The widespread use of opium and morphin for local action— injections and lotions — is based on an erroneous idea. Opium contains gum which is a demulcent, a rather expensive one, however, while its active principle, morphin, must be ab- sorbed before it can produce its effects, which are constitutional, not local. OFFICIAL PREPARATIONS OF OPIUM. The importance of opium and morphin are such that their actions and uses should be carefully studied in standard works of the day, and we shall pass to the minor members of the group after enumerating the official preparations. The danger that the patient will form the truly terrible opium habit from even a short use of the drug or of any of its derivatives should always be borne in mind, and when it is necessary to use them they should be masked. Hypodermics in pain have come to be almost synonymous with mor- phin in the minds of the laity. This idea should be uprooted both by the use of the method for many other substances and by avoiding it as much as possible with morphin. The odor and the taste 240 PHARMACOPEIA AM) PHYSICIAN. of opium and of the tincture, unfortunately, are well known and they should be disguised if possi- ble. To disguise the identity of opium and its prep- arations it is customary with some practitioners to employ the old designation thebaica for opium, tincture thebaica for the tincture. The use of the deodorized preparations of opium is also to be rec- ommended for this same purpose. The official titles, properly coming under the heading opium, are not only numerous, but varied and important. Opium and granulated opium are never used directly in the practice of medicine, but powdered opium and deodorized opium are fre- quently prescribed. Opii Pulyis. — IT. S. — When assayed, by the process given in the Pharmacopeia, this should yield not less than 12 per cent, nor more than 12.5 per cent, of crystallized morphin. This require- ment is somewhat higher than the provision adopted, for the International Standard, which limits the morphin contents of powdered opium to 10 per cent. Average Dose : IT. S. P. powdered opium is 0.050 (50 mg. or 1 grain). Opium Deodoratum . 2 — IT. S. — This is pow- dered opium which has been treated with purified petroleum benzin to remove the caoutchouc, wax, 011 and the odorous substances that are present; the alkaloidal strength and the dose of deodorized 2. This preparation is superior to the widely used pro- prietary preparation of opium “Svapnia.” over which it has the advantage of economy, activity and even general reliabil- ity, since the accompanying directions for assay are not alone accurate, but are readily followed by any one versed in chemical assay work. ANALGESICS AND SOPORIFICS. 241 opium are the same as for the official powdered opium. Extractum Opii. — TJ. S. — Assayed to contain 20 per cent, of morphin. This preparation is now little used, except in suppositories and the official opium plaster. Average Dose: 0.030 gm. (30 mg. or % grain). Pin: la: Opii. — U. S. — These are each composed of opium, 0.065 (1 grain), and soap 0.020 (1/3 grain ) . These pills constitute a very ancient form of administering opium. There are five liquid preparations, the least use- ful of which will be mentioned first : Yinum Opii. — U. S. — Containing 10 per cent, of opium in fortified white wine, aromatized with 1 per cent., each, of cinnamon and cloves. It re- sembles the well-known “Laudanum of Syden- ham.” Average Dose: 0.5 c.c. (8 minims). Acetum Opii. — IT. S. — Vinegar of Opium, for- merly known as black drop, Lancaster drops or Quaker drops, has long been known and extensively used. It contains 10 per cent, of opium and 3 per cent, of nutmeg in diluted acetic acid, sweetened with sugar. Average Dose: 0.5 c.c. (8 minims). Tinctura Opii. — L. S. — Tincture of Opium is the well-known and widely used laudanum, and consists of 10 per cent, of opium in diluted alcohol. Average Dose: 0.5 c.c. (8 minims). Tinctura Opii Camphorata. — TJ. S. — This, also known as paregoric or paregoric elixir, is the only one of the compound preparations of opium now official. It is so well known as a mild anodyne 242 PHARMACOPEIA AND PHYSICIAN. and sedative that further notice is not necessary. Average Dose: 8 c.c. (2 fluidrams). This amount contains about 0.03 gm. ( )/£> grain), each, of powdered opium, benzoic acid, camphor and oil of anise. Tixctura Opii Deodorati. — U. S. — Deodor- ized Tincture of Opium is practically a 10 per cent, aqueous extract of opium that has been treated with purified petroleum benzin to remove the odor- ous and other objectionable constituents, and sub- sequently preserved by the addition of 20 p£r cent, of alcohol. This, like the simple tincture of opium, is directed to yield, on assay, not less than 1.2 per cent, nor more than 1.25 per cent, of mor- phin in crystals. The average dose is 0.5 c.c. (8 minims) . While there has been some controversy as to who originated this particular preparation, there has never been any difference of opinion as to its possibilities and uses. From the sedative elixirs of nearly a century ago to the Scotch oats essence of the present day there have been many attempts to exploit deodorized or masked opium preparations, as harmless vegetable compounds. Another class of preparations, like “McMunn’s Elixir of Opium,” has been exploited as embodying some wonderful discovery in the treatment of opium. 3 The official deodorized tincture is in every way distinctly su- perior to all of these nostrums, because, as noted 3. “Papine” would be a gem among these if the claims made for it were true, hut we can not believe that any prep- aration of opium “containing the pain relieving principle (which we know to be morphin) can be “a safe opiate for children under one year.” This affords a good example of the audacity of the nostrum vendor who seeks to delude the physician and induce him to foster such vicious habits even in the cradle. ANALGESICS AND SOPORIFICS. 243 under deodorized opium, it has the advantage of economy, efficiency and reliability. There are but three other galenical preparations of opium official in the present Pharmacopeia. Tinctura Ipecacuanha et Opii. — U. S. — Liquid Dover’s powder. This is of practically the same strength as the well-known powder of ipecac and opium. Average Dose: 0.5 e.c. (8 minims). Pul vis Ipecacuanha et Opii. — U. S. — This has been noticed under ipecac (see Chapter IX). It contains 10 per cent., each, of ipecac and of pow- dered opium. Average Dose: 0.500 gm. (7^2 grains). Trochisci Glycyrrhiza et Opii. — U. S. — These have been previously noticed. MORPHIN AND CODEIN. The alkaloids, morphin and codein, are of nearly as much interest as opium. Morphin was discovered by Sertiirner, a German apothecary, in 1805, and was used in medicine as early as 1820. There are four official prepara- tions : Morphina. — U. S. — This alkaloid, obtained from opium, occurs as colorless or white shining rhombic prisms or as fine needles or as a crystal- line powder. It is odorless and has a bitter taste. Average Dose : 0.010 gm. (1/5 grain). Morphina Acetas. — U. S. — This salt of mor- phin should be kept in well-stoppered, dark amber- colored bottles, and a minute quantity of free ace- tic acid should be present to prevent decomposi- tion. Average Dose: 0.015 gm. (^4 grain). 244 PHARMACOPEIA AXD PHTSICIAy. Morphine Hydrochloridum. — U. S. — Like the acetate, this should be kept in well-stoppered dark bottles. Average Dose: 0.015 gm. grain). Morphines Sulphas. — U. S. — Like the other morphin salts, this should be kept in well-stop- pered dark bottles. Average Dose: 0.015 gm. ()4 grain). Sulphate of morphin is much the most fre- quently used in this country, while the hydro- chlorid is generally given the preference in Eu- rope. The acetate is the most readily soluble in water but is quite unstable, losing acetic acid on exposure to the air, and, as the alkaloid morphin requires 3,300 parts of the water for solution at ordinary temperatures, considerable care should be exercised in the use of old. and possibly decom- posed, samples of morphin acetate. While the new Pharmacopeia gives 0.015 gm. (14 grain) as the average dose of the salts of morphin. we believe that this is too high as the “average” dose. Codein and two of its salts are official : Codeina, codeina? phosphas, codeinfe sulphas. Codein, in addition to being obtained from opium, is also prepared from morphin by methyl- ation. It was discovered by a French chemist. E. Robiquet, in 1832. but was not generally used in the practice of medicine until many years later. It was admitted into the IT. S. Pharmaeoepia in 1880; the phosphate and the sulphate are now official for the first time. The sulphate is the form most frequently employed in this country, though it appears to be but little known abroad, where the phosphate is mainly used. The phosphate was ANALGESICS AND SOPORIFICS. 245 considered under ‘‘Expectorants.” Codein has been considered a somewhat uncertain drug, owing to its frequent contamination with morphin, but the Pharmacopeia provides a test for its purity, and particularly for detecting the presence of the more poisonous alkaloid. The phosphate being readily soluble in 2.5 parts of water, is particularly well suited for hypoder- mic use; or it may be prescribed alone in syrup or combined with hydrated chloral or the bromids ; in the latter case the mixture should be directed to be shaken before using. The average dose of codein or of any of its salts is 0.03 gm. (30 mg. or % grain). Apomorphi^l® Hydro chloridum. — IT. S. — which was also mentioned under “Expectorants,” has been recently brought to notice as a hypnotic, in doses of 0.002 (1/30 grain). It is said to have the great advantage of not producing a drug habit. Heroin and dionin are proprietary articles of the morphin group possessing some advantages, but they are not free from danger. The heroin habit is beginning to be common and should be carefully guarded against. Cannabis Ixdica. — U. S. — Indian Cannabis is a well-known member of the opium group. It occurs in dark-green or brownish compressed masses, having an agreeable narcotic odor and characteristic taste. It appears to have been used by the Hindoos from very early time. It was also known to the Egyptians and to Dioscorides, but it was not intro- duced into England until about 1835. Average Dose: 0.05 gm. (1 grain), but rarely used in substance. 24G PHARMACOPEIA AND PHYSICIAN. Extractum Cannabis Indict. — U. S. Average Dose: 0.05 c.c. (1 minim). Pinctura Cannabis Indicje. — U. S. — repre- sents 10 per cent, of the drug extracted with alco- hol. Average Dose: 0.5 c.c. (10 minims). At one time the cannabis indica was supposed to have great virtues as an antispasmodie, analgesic and narcotic, and it was highly recommended by a few physicians as a vasomotor stimulant, uterine stimulant, etc. It is now but little used and there seem to be few conditions in which one of the prep- arations of opium could not, advantageously, be used in its stead. 4 Two other members of the opium group are sanguinaria, which we have had occasion to men- tion elsewhere, and the feebly-acting Lactucarium. — U. S. Average Dose: 1 gm. (15 grains). Tinctura Lactucarii. — U. S. — This is a 50 4. It may be worth while to notice the importance attached to the extract of cannabis indica by the makers of bromidia, who claim that their preparation is the only hypnotic that has stood the test in every country for thirty years. Since all the other constituents are very commonly used, one must infer that they consider the “genuine imported extract of cannabis Indica of exceptional value. Bromidia, it is claimed by the manufacturer, contains 15 grains each of hydrated chloral and potassium bromid, and % grain each of genuine imported extract of cannabis indica and extract of hyoscya- mus, to the teaspoonful. Thus a single repetition of the dose — one teaspoonful — might prove fatal, since 30 grains of hydrated chloral have caused death ; but the manufacturers advise hourly doses so long as may be necessary to Induce sleep. The extravagant claims made by the manufacturers of this nostrum have Induced many physicians to use It in preference to prescribing the several official constituents ac- cording to Individual needs, and to-day it is offered direct to the public at cut-rate prices. ANALGESICS AND SOPORIFICS. 247 per cent, solution of lactucarium in diluted alcohol. Average Dose: 2 c.c. (30 minims). Syrupus Lactucarii. — U. S. — This is much more commonly employed than the tincture, its popularity being largely due to a nostrum. Average Dose : 8 c.c. (2 fluidrams) . THE ATROPIN GROUP. The atropin group includes the crude drugs yielding the mydriatic alkaloids, such as atropin, hyoscyamin and hyoscin, or scopolamin, all of the latter being closely related chemically. The actions of atropin and its congeners are so important and so complex that it is entirely beyond the scope of the present article to attempt any- thing like a complete description of them. The reader can not avail himself of this potent and im- portant class of agents without a careful study of their pharmacologic and therapeutic actions. We shall, therefore, call attention to a few more im- portant applications and contraindications without entering deeply into the reasons. Atropin is useful as an analgesic mainly when the pain is of spasmodic origin and when the appli- cation may be made directly to the nerve ends of the affected tissues. In the pains of lead colic this may be accomplished by the internal use of one of the preparations of belladonna, preferably a pill of the extract coated with salol or keratin. The most prominent action of atropin is seen in the dilation of the pupil, but the more rapidly act- ing and less enduring homatropin hydrochlorid is usually preferred for this purpose, if the object is merely to examine the eye — atropin, if it is de- 248 PHARMACOPEIA AND PHYSICIAN. sired to paralyze accommodation for some time, as in inflammatory conditions. While the mydriatic effect is so similar with the different members of this group, it must be remem- bered that they have very dissimilar actions on the brain. The crude drugs and their preparations belong- ing to this class are so numerous and so well known that it is hardly necessary to enumerate them. Be- sides Belladonna Boot and Leaves, Hyoscyamus and Stramonium Leaves, a member now official for the first time, is Scopola. Scopola. — U. S. — The dried rhizome of Scopola carniolica (Jacquin) (Fam. Solanacece ) , yielding, when assayed as directed in the Pharmacopeia, not less than 0.5 per cent, of its alkaloids, has little odor and a sweetish, afterward bitterish, acrid taste. Though described by Dr. Scopoli in 1771, it attracted but little attention from the medical profession until it was used in manufacturing “belladonna” plasters. Average Dose: 0.04 gm. (2/3 grain). Fluidextractum Scopola. — IT. S. Average Dose: 0.05 c.c. (1 minim). Scopolamine Hydrobromidum. — IT. S. — This is chemically identical with Hyoscins Hydrobrom- idum I". S. It has been used in the treatment of nervous excitement, particularly of the insane. It often induces quiet sleep at night — not usually in the day — and may also lessen sexual excitement. Atropin, on the other hand, has been used to stim- ulate the brain in cases of depression. Average Dose: 0.0005 gm. (0.5 mg. or 1/125 grain) . ANALGESICS AX I) SOPORIFICS. 249 Hyoscyaminje Hydrobromidum, U. S., and HyoscyamiilJ Sulphas. — II. S. — These are used very much as Hyoscin is. Average Dose: 0.005 gm. (0.5 mg. or 1/120 grain) . None of the mydriatic alkaloids should be used as soporifics except in case of urgent need, as the benefits may be more than counterbalanced by the disadvantages. Hyoscin and hyoscyamin are of lit- tle use directly in relieving pain; hence, they can hardly be considered as analgesics. Any of these alkaloids may be given alone as tablet triturates or as compressed tablets, hypoder- mically or alone in aqueous solution. The following is a common method of exhibit- ing belladonna, particularly in asthma : It. Tinctur* belladonnas fol. Tincturse lobelise, of each 3ii 10 1 Spiritus aetheris nitrosi, q. s. ad. . . 3 iii 100 1 Of this a teaspoonful is given every hour or two until relief is obtained. The bromids of ammonium, sodium or potas- sium may be used with the prescription given, but in that case adjuvant or aromatic elixir should be substituted for the spirit of nitrous ether, and, as in every case when bromids or iodids are combined with alkaloids, the mixture is directed to be shaken. The extracts of the crude drugs are much to be preferred to the alkaloids as additions to purga- tives, since the latter would be largely absorbed from the stomach, whereas the local action on the intestine is desired. 250 PHARMACOPEIA AND PHYSICIAN. THE ACETANILID GROUP. The enormous growth of the traffic in proprie- tary remedies mainly composed of acetanilid and allied substances is probably the most potent fac- tor in arousing physicians to a realization of the part they play — often unconsciously — in further- ing the selfish schemes of unprincipled manufac- turers. The Council on Pharmacy and Chemistry of the American Medical Association has shown that antikamnia, phenalgin, salacetin and am- monol are mere mixtures of acetanilid with other substances, and we can no longer prescribe these acetanilid mixtures under the impression that we are using true chemical compounds. It is probable that acetanilid figures more extensively in self- drugging than does any other single substance. The following are official : Acetanilidum. — U. S. — Acetanilid, antifebrin, phenylacetamid, the monacetyl derivative of anilin, occurs in colorless crystalline laminae or powder, permanent in air, odorless, of a slightly burning taste, and very slightly soluble in water. In was first prepared by Gerhard in 1852, but was not used medicinally until nearly thirty years later, when it was introduced under the trade- mark name of antifebrin. It is now employed very extensively, its extreme cheapness — less than 2 cents an ounce — causing it to be used as the basis of many pretended synthetics. Average Dose: 0.20 gm. (3 grains). Pulvis Acetanilidi Composites. — U. S. — This has been made official to serve as a substitute of uniform standard for the host of more or less similar compounds, such as we have enumerated ANALGESICS AND SOPORIFICS. 251 above, which have come into such unfortunate vogue. The official preparation consists of 70 per cent, of acetanilid, 10 per cent, of caffein and 20 per cent, of sodium bicarbonate. Average Dose: 0.3 gm. (5 grains). Acetphenetidinum. — U. S. — Acetphenatidin, better known as phenacetin, is official in the Brit- ish, German and other European pharmacopieas as Phenacetinum. It is officially described as Acet- para-phenetidin, a phenol derivative, the product of the acetylization of para-amido-phenetol. Phenacetin occurs as white glistening scales or a tine crystalline powder, odorless and nearly taste- less. It is soluble in 925 parts of water and in 12 parts of alcohol. Antipyrinum. — U. S. — Antipyrin is official in France as Analgesin, in Great Britain as Phena- zonum, and in Germany as Pyrazolonum — phenvl- dimethylicum. Chemically, it is described as phenyl-dimethyl-pyrazolon, and is obtained by the condensation of phenyl-hydrazin with aceto-acetic acid and subsequent methylation of the product. Antipyrin occurs as a colorless, almost odorless, bitter tasting, crystalline powder, that is readily soluble in water and soluble in about 1 part of alcohol. 5. It should be noticed that the dope of acetanilid in the* mixture is larger than the official dose of acetanilid ; yet it is supposed to act more effectively when mixed with so- dium bicarbonate. It is to be regretted that such a combi- nation has been given official recognition. The reason, of course, is evident — persistent advertising of certain nostrums has created an abnormal demand for acetanilid combined with a supposed heart stimulant. But, as it Is extremely improb- able that caffein does counteract the harmful effects of acetanilid, it is not wise to recognize such a combination even to meet a supposed demand. 252 PHARMACOPEIA AND PHYSICIAN. Average dose: 0.250 gm. (4 grains). Antipyrin was first prepared by Dr. L. Ivnorr of Erlangen, in 1884; it was investigated physiologic- ally by Professor Filehne, who reported it as an active antipyretic. It will be more satisfactory to consider the therapeutics of these antipyretics collectively, with occasional comments on the separate members of the group. They are mostly used for headache and for the reduction of temperature in fevers of an intermit- tent type, but it must not be forgotten that they do not remove the underlying cause, and that the use of these drugs in continued fevers is liable to be harmful, since the temperature is sure to return to its former height, or to go even higher, when the action of the antipyretic has worn off. The alarming collapse that may follow even a moderate dose of acetanilid serves as a warning against its use when there is reason to suspect any tendency to that condition. On the other hand, a sudden lowering of the temperature in fever may result in collapse symptoms wholly independently of the nature of the remedy employed. Acetanilid has the greatest and phenacetin the least tendency to produce collapse among the official preparations of this nature. It is to overcome this tendency that caffein is used in the official compound acetan- ilid powder, but it is doubtful if it is of any great value in guarding against this collapse. There can be little doubt that many of the sudden deaths, of which we so constantly read, occurring without ap- parent cause on the streets and elsewhere, are in reality due to overdosing with nostrums containing acetanilid. ANALGESICS AND SOPORIFICS. 253 Women should be particularly cautioned against the promiscuous use of nostrums of this type dur- ing menstruation. When it is remembered that antipyrin and ace- tanilid are derived from phenylhydrazin, and anilin — active blood poisons — it is not surprising that the official derivatives possess the properties of these drugs in a minor degree. A peculiar cyanosis is often seen about the ears, the lips and the nails, particularly after large doses of acetanilid, due to its action on the red blood cells ; this has been noticed even in the absence of hemoglobin in the blood. Acetanilid in large doses causes destruction of red blood cells, and methemoglobin may be thrown into the plasma. The collapse seen after ingestion of the anti- pyretics, particularly acetanilid (least with phen- acetin) is due to several causes. Probably the most frequent cause is the mere lowering of the temper- ature which exposes the collapse actually existing but hidden by the high temperature. This result is not to be charged to the antipyretic. It is treated exactly as collapse from any other cause would be — by stimulation. Yery large doses of the antipyretics act on the heart muscle, causing de- pression. and on the vasomotor center, causing col- lapse. The acetanilid habit is not rare and it leads to a deplorable condition, but the symptoms generally disappear when the drug is withdrawn. Profuse perspiration is a disagreeable effect, more frequently seen after acetanilid and anti- pyrin than after phenacetin. If this is so annoy- ing as to demand interference, a hypodermic in- 254 PHARMACOPEIA AND PHYSICIAN. jection of 0.5 mg. (1/150 grain) of atropin will be found effective. Bedness and irritation of the skin are frequently seen after the use of the various antipyretics of this group. They are probably due to vasomotor changes. Antipyrin in solution has been used extensively to check the bleeding of superficial wounds, and all the various members of this group are to some ex- tent antiseptic. While so much space has been devoted to the contraindictions and untoward effects of these agents, it is not with a view of discouraging their use, but rather that the physician may avoid the disappointments which arise from their use in un- favorable conditions. Acetanilid may be given alone in powder or in capsules, in adjuvant or aromatic elixir, or sus- pended in syrup or mucilage of acacia. The com- pound acetanilid powder affords a convenient form for the relief of headache. A dose of 0.3 gm. (5 grains) in powder or capsule is usually effective; this may be repeated once in an hour if necessary, but further repetition is to be avoided. Compressed tablets of such insoluble substances as phenacetin and acetanilid are not recommended as they disintegrate slowly. An acetanilid powder, containing ammonium carbonate instead of caffein, is used in the German Hospital of Philadelphia, 6 when it is desired to avoid the cerebral stimulation of caffein. 6 . R. Acetanilid Sodii bicarb., of each grs. xxii 1 1 5 Ammon, carb aa grs. xi |75 This is sufficient for ten powders of about 0.3 gm. (5 grains) each, one being given every three or four hours to reduce fever. For headache one is given and repeated, if necessary, in an hour. ANALGESICS AND SOPORIFICS. 255 Antipyrin is very soluble in water and in alco- hol, and hence it may be given in simple aqueous solution, in aromatic elixir or in powdered form. Acetphenetidinum (phenacetin), being less ob- jectionable than acetanilid and antipyrin, may be expected to replace them very largely now that the price is reduced. Its insolubility in water has led to its extensive use in powder and in capsules. A combination of phenacetin, caffein and sodium bromid has attained considerable popularity; these may be combined in various ways. i. * * * * * 7 CHEMISTRY OF THESE PREPARATION'S. A brief review of the chemistry of the antipy- retic group will show the relationship of the various members to each other. Quinin being a derivative of quinolin, many at- tempts were made to produce it synthetically, with the resulting discovery of a number of quinolin derivatives which possess antipyretic properties. i. R. Acetphenetidlni (phenacetin) ... .grs. xv 1 Caffein grs. viil 5 Sodli bromldi 31 4 Elixir adjuvant 51 30 The mixture is to be shaken and two teaspoonfuls given as a dose. This is often used for headache, one dose being usually sufficient. Still another, widely used, mixture containing acetanilid, is a migraine elixir that is being exploited by a number of manufacturers. A representative formula, for a preparation of this kind, may be given as follows : R. Acetanilidi gr. xxx 21 Caffeinse gr. iii |2 Sodii bromidi 3ii 81 Alcoholis 31 4 Elixir aromatici, q. s. ft Jiii 100 1 Average dose 5 c.c., or 1 teaspoonful. If 20 c.c. of tincture of cardamon be added to this, or if adjuvant elixir (which is also official), be used instead of the aromatic, the appearance of the mixture will be much enhanced and the psychical effect increased. 250 PHARMACOPEIA AXD PHYSICIAN. but all of them dangerous because of their ten- dency to produce collapse. All of these are now practically obsolete. Another substance having antipyretic collapse action is phenylhydrazin, which is of interest be- cause of its derivative, antipyrin. Hydrazin N,H 4 (or H,N — NH 2 ), which is formed by the union of hydroxylamin and ammonia, usually exists in com- bination with an organic radical. Starting with the benzene ring, C 6 H G , or H C X X HC CH I I HC CH \ x C H benzene phenol (carbolic acid) is formed by replacing an H with OH. If this OH in turn be displaced by the hydrazin radical, phenyl hydrazin is formed thus : C[OH H]HN-NH> x x HC CH I I + HC CH x X C H phenol + hydrazin = CH3N2+H2O HC CH I I HC CH X X C H phenyl-hydrazin + water. Though many derivatives of phenyl-hvdrazin have been exploited, antipyrin and its compounds are the only ones in general use. When the practitioner uses drugs which at best are so potent for harm he will do well to employ them in their simplest form rather than in such unofficial combinations as hypnal (chloral and an- ANALGESICS AND SOPORIFICS. 257 tipyrin) or salipyrin (salicylic acid and antipy- rin) . Acetanilid or phenyl-acet-amid is obtained by the action of boiling glacial acetic acid on anilin, or phenyl-amid, as it may be termed. By intro- ducing “acet” before “amid” the chemic name is derived. CNH[B HO]OC.CH, CNH. OC.CH 3 + H 2 0 HC CH HC CH 1 1 + — 1 1 HC CH HC CH \ / \ / Phenyl-amid + acetic = acetanilid + water (anilin) acid When other acid radicals replace that of acetic acid similar compounds are formed, which are in no wise superior to the official. Thus we have benz- anilid and exalgin (or methyl acetanilid), the lat- ter differing from acetanilid only in having a CH 3 group replacing an H. It will be understood from its chemistry why acetanilid can be prepared so cheaply and, there- fore, why it is so extensively employed in the nos- trum traffic. Phenetidin is important as the basis of the phen- acetin group. Chemically it is the ethyl ether (sulphuric, so called) of amido-phenol. If an amid group (NH„) replaces the H in the para position (opposite to the OH) of phenol COH / \ HC CH I I HC CH \ / C H Phenol. COH / \ HC CH CH CH \ / c nh 2 Para-amido-phenol 358 PHARMACOPEIA AND PHYSICIAN. we have para-amido-phenol, and if the OH is then replaced by ether we have phenetidin. Various acid radicals may replace an H of the NH 2 . If it be the acetic radical we have phenacetin, if lactic acid we have lactophenin. These formulas may appear complex, but a care- ful examination of them will show the relationship existing between the various members of the group. If the practitioner finds the official phenacetin un- suited to his purpose in a given case, it is not probable that another compound, differing merely in the nature of an acid radical, will prove more beneficial. Among the phenetidin series there are, besides the official phenacetin, many in which the syllable “phen” indicates the phenetidin source. They in- clude phenocoll, salophen, lactophenin and many others. We shall have occasion to mention urethane ethyl carbamate) among the hydrated chloral group, and it may be said that several of its deriv- atives have been used as antipyretics, but they do not merit further consideration here. In connection with the subject of antipyretics we may mention a number of substances which, except historically, are now of little interest. Kairin, discovered by Dr. 0. Fisher in 1882, was the first of the coal-tar compounds to be introduced as an antipyretic on the strength of physiologic experiments. It was also one of the first of the medicinal synthetic chemicals to be patented. The older physicians may remember its widespread use and some of the exaggerated claims that were made for it and how, despite this, it fell into dis- favor and was soon forgotten. ANALGESICS AND SOPORIFICS. 259 Thallin, made by Dr. Skraup in 1884 and inves- tigated in the clinic of Nothnagel, soon shared the fate of kairin, despite liberal advertising. Resorcinol. — IT. S. — Rescorcin (U. S. P. 1890) discovered by Hlasiwitz and Borth about 1862, was used as an antiseptic and later as an antipyretic, but was found to be too dangerous for the latter purpose. It may be absorbed even after external application, when its effects resemble those of phenol (carbolic acid). The official salicylic acid, discovered in 1839, was introduced as an antiseptic in 1873 and later as an antipyretic. The salicylates now find their greatest usefulness in the treatment of acute rheu- matism. They will be discussed later. THE HYDRATED CHLORAL GROUP. The hydrated chloral group includes, besides hy- drated chloral, chloralformamid (chloralamid), paraldehyd, ethyl carbonate (urethane), sulphon- methane (sulphonal) and sulphonethylmethane (trional). Several of these preparations are so well known that we may dismiss them in a few words, but some of them may be profitably dis- cussed at greater length. It is easy to drug anyone into unconsciousness, but the members of this group do not possess cura- tive properties and at most they only secure rest and sleep for the patient. Hydrated chloral is dangerous and we wish to point out some of the dangers attending its use, either alone or in the nostrums which contain it. 8 8. Attention has been called to Bromidia, which is di- rected to be given in as much as teaspoonful doses every hour until sleep Is produced, pain being mentioned as one 260 PHARMACOPEIA AND PHYSICIAN. All authorities agree that it is unjustifiable to use large doses of hydrated chloral, either alone or in combination with other official drugs. When a moderate dose of hydrated chloral fails to induce sleep in cases of severe pain, it is very much more rational to give a dose of morphin, or other anal- gesic, than to repeat the hydrated chloral indefi- nitely. The hydrated chloral habit is not rare, and if its sale at cut rates in the shape of nostrums with fanciful names is to go on unchecked, we can hardly hope to see any diminution of the baneful practice. When we employ hydrated chloral and sodium, or potassium bromid in simple solution it is with full cognizance of the danger, but because the exigencies of the case demand their use, and we only use them with caution . * * * * * * 9 In a general way the contraindications for hydrated chloral are the same as for chloroform. In the present addition of the Pharmacopeia it is official as : Chlcralum Hydkatum. — IJ. S. — Hydrated chloral. of the indications for its use. Since hydrated chloral is not an anesthetic, except in unsafe doses, it is readily seen how dangerous this advice is, particularly when we are dealing with such intense pain as that encountered in appendicitis, even admitting that the preparation contains the other in- gredients claimed. 9. A fairly safe and very efficient hypnotic commonly used in Bellevue Hospital in New York affords a convenient form of using sodium bromid with hydrated chloral. R. Chloral! grs. xx 1 30 Sodii bromidi grs. lxxx 5 30 Syr. aurantii cort 3iv 16 Abus q. s. ad 3i 30 M. Two teaspoonfuls are given at a dose, and this may be twice repeated at intervals of an hour if necessary, but more than two doses are rarely required in the absence of severe pain. The hydrated chloral may be slightly increased in the pre- scription, in which case the dose should not be repeated more than once. ANALGESICS AX D SOPORIFICS. 261 Average Dose: 1 gin. (15 grains). Of the unofficial, more or less closely related drugs, hypnal (antipyrin and hydrated chloral) has been mentioned. Dormiol is a combination of amvlene hydrate and hydrated chloral, while chloralose, a combination of hydrated chloral and glucose, partakes of the action of morphin and is rather expensive. Chloretone, a more recent product, is not entirely devoid of danger and is not always so certain in its action as hydrated chloral, while butyl chloral hydrate or croton chloral hy- drate, is one of the older compounds that has been found wanting and is now little used. Of the official compounds of this group we have : Chloraeformamidum. — U. S. — Chloralforma- mid. Chloralamid. This has practically the same action as therapeutic doses of hydrated chloral, the latter being formed in the body by decomposition of chloralformamid. Average Dose: 1 gm. (15 grains). Paraldehydum. — U. S. — Paraldehyd, a trans- parent liquid, is slower in its action than hydrated chloral, but also safer. It has the disadvantage of a persistently disagreeable taste and odor. It is locally irritant and should not be used in irritable conditions of the stomach. It may be prescribed dissolved in 10 parts of water or in aromatic elixir, and is best administered cold, or followed by a cold drink. Average dose: 2 c.c. (30 minims). SulphonmethajStum. — IT. S. — Sulphonmeth- ane, sulphonal, diethylsulphonedimethylmethane, and SULPHONETHYLMETHANUM. — IT. S. — Sulphon- ethylmethane, trional, disulphonmethylethyl- 2G2 PHARMACOPEIA AND PHYSICIAN. methane, may be considered together as they differ chemically only in the addition of an ethyl group in the latter. Average Dose (either) : 1 gm. (15 grains). The therapeutic action of these two preparations is practically identical, and the closely related tetronal might also be included in this statement. Trional is somewhat more soluble than sulphonal. While these substances are safer than hydrated chloral they are not wholly free from danger, as fatal cases of poisoning have been reported and the sulphonal and trional habits, while of more recent origin, bid fair to equal, if not to exceed, the chlo- ral habit in the number of their victims. These agents are usually given in powder, and owing to their slow absorption, should be given about two hours before they are expected to act. To insure more speedy action they may be given in solution, for which purpose they are dissolved, or at least suspended, in a cup of hot milk. JEthylis Carbamas. — U. S. — Ethyl Carbam- ate, urethane. This is a new official preparation which is claimed to be much safer than hydrated chloral, to which it would be distinctly superior but for the fact that its action is not so certain and because tolerance is soon acquired. It is best given in water, in which it is very soluble. The average dose is 1 gm. (15 grains). THE BROMID GROUP. The bromid group is so well known that it re- quires little therapeutic consideration here, but it is of considerable historic, as well as of practical, interest. Potassium bromid was introduced by Balard about 1826. who supposed it to have proper- ANALGESICS AND SOPORIFICS. 263 ties analogous to those of potassium iodid. It was not until some time after 1850 that the present, sedative, uses of the bromids were accidently dis- covered. During the past four decades the sev- eral alkaline bromids have received considerable attention and several of them are now official in every pharmacopeia. In our own Pharmacopeia, in addition to monobromated camphor, hydro- bromic acid and the hydrobromids of a number of alkaloids, we have ammonium, potassium, lithium, calcium, sodium and strontium bromids official. The average dose of any of these alkaline bromids is 1 gm. (15 grains). The abuses that have arisen in connection with substances belonging to this group are largely due to the misrepresentations that are made in connec- tion with the efficiency or the character of the nostrums containing them. Strontium salts, particularly the bromid, were brought forward some years since, at exorbitant prices, as being infinitely superior to the corre- sponding compounds of other elements. Experi- ence has shown that, in the main, these claims were unfounded, though many, even now, claim that strontium bromid disturbs the stomach less than the corresponding sodium or potassium salt. An- other claim that is frequently made by manufac- turers of nostrums like “Peacock’s Bromides,” is that they use “chemically pure” salts. Exactly what is meant by this claim it is difficult to say, but the Pharmacopeia gives us a number of readily ap- plied tests by which the salts themselves may be tested. The manufacturers of nostrums, on the other hand, not infrequently add the very sub- stances that are considered contaminations. CHAPTER XI. CIRCULATORY STIMULANTS. The subject of circulatory changes is entirely too extensive for anything like a comprehensive treat- ment in the limited space that can be allotted to it here. We shall endeavor, however, to discuss some of the indications for influencing these changes and try to indicate how they may be brought about. The term “heart tonic” has been so loosely em- ployed that it is better to avoid it altogether, or to use it only with reference to those drugs which, acting directly on the heart, improve the muscular tone. The heart is but one, and in some respects even a minor, factor in the question of blood pressure, on which the state of the circulation largely depends. Hence, while a “heart tonic” implies an agent which improves the action of the myocardium, the actual changes in the circulation depend not alone on the amount of work done by the central organ, but on the combination of that and the constriction or dilatation of the blood vessels. Since the relative amounts of blood existing in the veins and arteries, and the amount which passes through a certain area or organ in a given time are dependent on several more or less closely related factors, we may direct our efforts toward influencing one or more of these factors when we wish to increase or diminish the blood supply of an organ, or when we wish to hasten the transfer of blood from veins to arteries. CIRCULATORY STIMULANTS. 265 An increase in the rate of the heart or strength of the beat, without a compensating change, either in the heart itself or in the blood vessels, will, of course, increase the general circulation, and con- versely, a diminished action would lessen the cir- culation, but so delicately is the complex circula- tory mechanism adjusted that such a simple change probably never occurs alone in the intact body, though it may at times predominate over other accompanying changes. THE MECHANISM OF STIMULATION. The simplest means of increasing the blood pres- sure consists in increasing the strength of the in- dividual beats, whereby the heart is more com- pletely and more forcibly emptied, and securing just enough slowing to enable the heart to dilate more fully and to become filled with a larger vol- ume of blood. These two actions insure a larger volume of blood being thrown into the aorta in a given length of time than occurred under previous conditions. An increased volume of blood with in- creased force, must, of course, insure an increased circulation in those areas in which there is no great change in the caliber of the smaller vessels. A high blood pressure on the other hand may be most simply reduced by slowing the heart with- out increasing its strength, or by acting on the ves- sels peripherally or through the vasomotor centers, causing dilation. The accumulation of an undue amount of blood in the veins is relieved by increasing the efficiency of the heart as mentioned for raising the blood pressure— by slowing and strengthening its beat — for. as we have seen, this improves the drainage 200 PHARMACOPEIA AND PHYSICIAN. from the veins by lengthening the diastole, while the strengthening throws a larger volume of blood into the arteries. We may arrange the agents affecting circulation into two groups as follows : Those mainly affect- ing the heart, directly or indirectly; those mainly affecting the vessels, directly or indirectly. The most important group of circulatory stim- ulants consists of digitalis and a number of sim- ilarly acting substances. While, as is well known, barium chlorid has to some extent a similar action to digitalis, nearly all the other members of this group that are of therapeutic importance are somewhat allied chemically; for the most part the active principles of these drugs are glucosids or resins. The exact chemistry of the drugs of this class is still obscure, despite numerous investiga- tions, and it demands but little consideration here ; their pharmacologic action, however, serves to ex- plain their therapeutic indications, and may aid in choosing the one best suited to a given condi- tion. The circulatory conditions demanding stimula- tion are mainly those in which undue relaxation oc- curs, and in which an imperfectly acting heart, in- cluding such conditions as valvular insufficiency and stenosis, permits the blood to accumulate in the veins. Any increase in the work of the heart must tend to relieve these conditions, particularly if there is at the same time just sufficient slowing to secure complete distention of the heart with blood during diastole. An increase in the strength of the contraction more completely squeezes the venous blood out of the heart muscle, which is then supplied with a CIRCULATORY STIMULANTS. 267 larger proportion of arterial blood. The increased force of the pulse wave must first be felt more strongly in the coronary artery than elsewhere, since there is less inertia to be overcome in the much shorter column of blood between the aortic valve and the opening into the coronary artery. The longer diastole then permits a more perfect supply to the capillaries in the heart, thus improv- ing the nutrition of the heart to an even greater de- gree than would correspond to the extra work thrown on the ventricles by their being compelled to contract against an increased arterial pressure. As we have just said, the slowing of the heart should be just sufficient to enable the heart to be- come fully distended, for a greatly slowed heart would suffer in lessened nutrition, because, other things being equal, the rate of flow through the coronary circulation varies with the number of the pulsations in a given space of time. This improved nutrition of the myocardium is the first essential for a sustained increase in the force of the beats, either from a more energetic ac- tion of the imaltered heart or after hypertrophy; because, however, such a muscle might be stimu- lated to unusual activity, exhaustion and paralysis must follow unless nutrition keeps pace with the work performed. Langendorff has shown experi- mentally that the energy of the heart is enor- mously influenced by the available blood supply. A drug might affect one or more phases of the heart beat, or the local and central action may be in part antagonistic and the effect on the blood pressure in the general circulation will in the lat- ter case be dependent on the kinds of influence and the degree to which each is excited. Slight slowing with increased strength of con- 2C8 PHARMACOPEIA AX D PHYSICIAN. traction may improve the nutrition, and it will be readily understood why it is difficult to secure equally perfect nutrition of the heart when it is made to beat more rapidly, since the only factor here which makes for an improved coronary circu- lation is the more frequent squeezing out of venous blood by the contractions while all other conditions are unfavorable, a greater number of contractions, each throwing out less blood and meaning more energy expended for a given amount of work per- formed — a more frequent overcoming of the iner- tia of the blood in the arteries — so that a very rapid heart soon exhausts itself. For these reasons we do not often seek to raise blood pressure or to improve the general circulation by increasing the rate of the heart unless it is extremely slow. Shock and collapse are conditions that are due to depression of the respiratory, cardiac and vaso- motor centers. The depression of the vasomotor center permits the vessels to dilate and the blood gravitates to the vessels of the splanchnic area, which are capable of holding a very large amount. This dilatation is accompanied by a fall of pres- sure in the general circulation, less blood goes to the centers and to the coronary circulation, the heart beats more feebly and the respiration be- comes weaker. This condition obviously calls for prompt stimulation of the circulation. It is ap- parent, however, that a stimulation of the heart alone would only result in increased work while its own nutrition would not be correspondingly improved because the pressure in the coronary cir- culation can not be greatly increased while the voluminous vessels of the splanchnic area offer CIRCULATORY STIMULANTS. 2G9 cavernous spaces for the blood which is pumped from the heart. Stimulation of the constrictor mechanism of the vessels is urgently demanded in collapse, and this is secured in the mildest cases by gravity determin- ing the blood to the head when the head is placed lower than the body. The centers are toned up by the better blood supply, and this increased tone of of the vasomotor center causes constriction of the splanchnic vessels, raises the blood pressure and improves the general circulation, which in turn further tones up the centers as well as the heart, which is also stimulated by the improved tone of the cardiac center. The respiration is improved at the same time owing to the improved tone of the respiratory center. Dr. George Crile has devised a pneumatic suit whereby pressure may be applied to the surface of the limbs, thus forcing a large amount of blood into the body and head, and gravity (lowering the head) may be made to assist in driving it to the head — the essential fact being to supply the medulla oblongata with blood. PHYSIOLOGIC SALT SOLUTION. Heat, mainly supplied by hot water bottles, should be used with any other measures in shock. The amount of fluid in the vessels may be consid- erably increased by injecting, under aseptic pre- cautions, into a vein, or even under the skin, nor- mal saline solution, or as it is better to term it, physiologic salt solution, made by dissolving 9 grams of sodium chlorid in enough water to make one liter, (approximately 132 grains of sodium chlorid to 1 quart of water.). The solution should 270 PHARMACOPEIA AND PHYSICIAN. be boiled (to render it sterile) and then cooled to about 40° C. (104° F.). As noted above this solution may be used hypodermically or it may be injected directly into a vein. Another, and at times a very satisfactory, method of attaining the same result is to inject slowly one or two liters of this solution into the rectum, whence it is readily absorbed into the circulation. Drugs which act on the vasomotor centers are indicated in collapse but the simple means just enumerated serve, as explained, to tone up the centers in mild cases by an improved blood sup- ply, and they are of course preferable to mere stimulation by drugs. Then, too, in proportion to the urgency of the case is the difficulty of secur- ing stimulation of the centers. In profound shock the stimulants of the vasomotor centers ap- pear to have no lasting effect, or to increase the trouble. In collapse of a mild character, however, a vaso-constrictor acting more powerfully on the vessels of the splanchnic area causes the general blood pressure to rise, more blood goes to the cen- ters, and they are placed in a better tone, exactly as is the case when gravity sends the blood to the head. Hot alcoholic drinks are very commonly em- ployed in collapse and shock; they probably act reflexly from the stomach. Some clinicians maintain that morphin im- proves a weakened heart. As a depressed center is less susceptible to shock from reflex influences, morphin may lessen shock or depression due to pain and the center will then be able to exert a better influence on the heart. It has often been claimed that opium or morphin caused an in- CIRCULATORY STIMULANTS. 271 creased supply of blood to the brain by dilating the vessels of that organ, and this may account for an increasd circulation in the cardiac center and hence an improvement in the heart. The de- pression of the respiratory center by morphin is rather strong evidence against any stimulation of the cardiac center however. Morphin has no direct action on the heart and its vasomotor effects are variable. THE DIGITALIS GROUP. The pharmacologic action of digitalis and that of its available active principles have been more extensively studied than has been done in the case of any other member of the group. The isolated frog’s heart, and later the mammalian, has been used to determine the action on that organ apart from the influence through the centers. The rate of the isolated mammalian heart is either in- creased or little affected by digitalis or its prin- ciples, but Gottlieb and Magnus found that the strength of the individual contractions is increased by it and that more actual work is done by the isolated heart. In the intact mammal digitalis slows the heart by stimulation of the vagus cen- ter, and the strength of the beat is increased by the action on the myocardium. The vasomotor centers are stimulated at the same time. The direct results of these several actions have been de- tailed in the introductory paragraphs. Digitoxin, the most active of the principles that have been isolated from digitalis, has essen- tianllv the same action on the circulatory system as the drug itself, but being insoluble in water it is slow in producing its effects. Albert Fraenkel has 272 BHARMACOPEIA AND PHYSICIAN. found that about sixty hours elapsed after a single effective dose was injected, hypodermically, into a cat before the typical action was induced. Digitalin, or “Digitalinum verum,” is somewhat more soluble in water and its action was elicited in twenty-four hours after a dose, corresponding in activity to that of digitoxin just mentioned, was injected into a cat, while strophanthin (ob- tained from strophanthus seeds), which is very soluble in water, produced its effects much more rapidly. The therapeutic action of these three sub- stances is very similar, but Gottlieb and Magnus found that digitoxin is capable of restoring an irregularly beating heart to rhythmic pulsations to an astonishing degree ; indeed, they were able to restore isolated and perfused hearts to strong reg- ular beats after they had gone into delirium cordis. Digitalis and other members of this group have the great disadvantage of causing cumulative ef- fects when used continuously for some time. Digi- toxin produces these effects more readily than strophanthin and digitalin. Fraenkel was able to continue the administration of digitalin daily for many weeks at near the toxic dose without cumulative action. No habituation occurred in this period, however, thus disproving the claims of Heide, based on a much more shorter period of ex- perimentation, that such takes place. Gastric irritation is the first evidence of a toxic action from a single toxic dose or from cumulative action, and digitalis, or any of its congeners with- out exception, must be stopped for a time when cumulative effects are seen. When the heart is slowed by any member of the digitalis group the action is very persistent. CIRCULATORY STIMULANTS. 273 Fraenkel concludes that the duration of the ac- tion on the heart is proportioned to the stability of the union which takes place between the drug and the mechanism affected, but that the interval elapsing between the time of administration and the beginning of the action is proportional to the insolubility of the principle. Gottlieb and Magnus in experimenting on the isolated heart found that digitoxin caused a constriction of the coronary arteries, but that this did not occur after stroph- anthin. The following official drugs belong to the digi- talis group. As noted before, there are other drugs and chemicals that possess a somewhat sim- ilar action, but it must be evident to all that noth- ing is to be gained, and that much harm may re- sult from giving heed to unwarranted and exagger- ated claims of the nostrum maker who lauds a preparation which ostensibly depends on some little known drug, such, for instance, as the several species of cactus. By far the most interesting as well as the most important of the official drugs of the group now under consideration is: Digitalis. 1 — U. S. — This consists of the dried 1. From what we know of the chemistry of this partic- ular drug, and from the action of the known isolated proxi- mate principles, it would appear that in this connection it was particularly unfortunate that the committee on revision did not see its way clear to adhere more strictly to the pro- posed international standards for the formulas of potent med- icaments and direct, for the extraction of digitalis, the pro- posed 70 per cent, alcohol in place of the diluted alcohol of the U. S. Pharmacopeia. The stronger alcohol would have had the advantage of insuring a more ready and more com- plete solution of the active principles, of answering better as a preservative and of materially reducing the amount of inert extractive now contained in the official tincture. 274 PHARMACOPEIA AND PHYSICIAN. leaves of Digitalis purpurea , collected from the sec- ond year’s growth at the commencement of flower- ing. This drug is official in all pharmacopeias and is generally considered as being particularly sus- ceptible to chemical change. It should be care- fully preserved and should not be kept for more than one year. Average Dose: 0.05 gm. (1 grain). While the chemistry of digitalis is far -from be- ing thoroughly understood, there are a number of proximate principles derived from digitalis that are now being marketed in a commercial way and which have well-defined chemical as well as physio- logic properties; several of them are being ex- tensively used in this country as well as abroad. The most potent of these unofficial articles is : Digitoxin : This, as has been noted before, is sol- uble in alcohol but is nearly insoluble in water. The older and in some respects better known French preparations, variously called digitalin, crystallisee, or French digitalin, closely resemble digitoxin in physical properties and also in physio- logic activity. Digitalin (Digitalinum verum, Kiliani) : This is a white amorphous glucosid that is readily sol- uble in alcohol but only slightly soluble in water. While it is less toxic than digitoxin and may be given in much larger doses, it closely resembles that principle in its therapeutic action and uses. Digitin (Merck) : This is also readily soluble in alcohol and only slightly soluble in water. While still available it is now generally thought to be physiologically inactive as a circulatory stimu- lant. Digitalein ( Schmiedeberg) : This is readily CIRCULATORY STIMULANTS. 275 soluble in water and is probably a mixture of sev- eral proximate principles. Digitalin “German” : This occurs as a yellow- ish white, amorphous powder that is soluble in both water and alcohol. It is said to consist of a variable mixture of Digitalinum verum (Kiliani), digitalein and digitonin. The following are official : Extractum Digitalis. — U. S. — This is made from the fluidextract by evaporation. Average Dose: 0.01 gm. (10 mg. or 1/5 grain). Fluidextractum Digitalis. — U. S. — Fluidex- tract of Digitalis is made with diluted alcohol. Average Dose: 0.05 c.c. (1 minim). Infusum Digitalis. — U. S. — Infusion of Digi- talis contains 1.5 per cent, of digitalis, 10 per cent, of alcohol and 15 per cent, of cinnamon water. Average Dose: 8 c.c. (2 fluidrams). Tixctura Digitalis.— U. S. — This now repre- sents 10 per cent, of the crude drug in diluted alcohol in place of 15 per cent, as formerly offi- cial. Average Dose: 1 c.c. (15 minims). Strophahtiiinum. — U. S. — This is a glucosid, or mixture of glueosids, obtained from strophan- thus. Average Dose: 0.003 gm. (0.3 mg. or 1/200 grain). Strophanthus. — U. S. — This consists of the ripe seeds of Strophanthus Kombe. It is preferably administered in the form of the official tincture. Tinctura Strophanthi. — IT. S. — This prep- aration now represents 10 per cent, of the drug in 65 per cent, alcohol, and is double the strength of 276 PHARMACOPEIA AND PHYSICIAN. the tincture official in the U. S. Pharmacopeia, 1890. Average Dose: 0.5 c.c. (8 minims). Apocynum. — U. S. — This is the dried rhizome of Apocynum cannabinum, or of other closely allied species of Apocynum. This drug is said to have been used by the American Indians in various ail- ments, and has long been in use as a household remedy. More recently it has again attracted at- tention by its possible uses as a circulatory stimu- lant, though the practical results that have been attained so far do not appear to warrant its use in all cases. The only official preparation is: Fluidextractum Apocyni. — U. S. — The Fluidextract of Apocynum is directed to be made with a mixture of 10 per cent, of glycerin, 60 per cent, of alcohol and 30 per cent, of water. Average Dose: 1 c.c. (15 minims). Conv allaria. — TJ. S. — This consists of the dried rhizome and roots of Convallaria majalis. Average Dose: 0.5 gm. (7y 2 grains). Fluidextractum Convallaria. — TJ. S. — This is made with a mixture of 65 parts of alcohol and 35 parts of water. Average Dose: 0.5 c.c. (8 minims). THERAPEUTIC ACTIONS OF THE DIGITALIS GROUP. Digitalis will he referred to under the heading of diuretics (Chapter XIII), for which purpose the infusion is usually to be preferred. As a circulatory stimulant one of the drugs of the digitalis group is indicated when the heart is weak and rapid and the blood pressure low, con- ditions which arise under a variety of circum- stances. CIRCULATORY STIMULANTS. Al- in cardiac dilatation with weak systole digitalis affords an ideal remedy as may be readily under- stood from the pharmacologic action. In pneu- monia the right ventricle suffers primarily and digitalis is indicated, for, while it affects the right ventricle less than the left, and the auricle least, this does not affect its usefulness in this condition, because the nutrition of the heart — both left and right — is supported by the improved coronary cir- culation, a most important factor, as we have seen, when extra work is thrown on the heart, and the pulmonary circulation is not affected by the gen- eral vasoconstrictor action of the digitalis. In this connection, the lengthened diastole, while it undoubtedly affords a better chance for the empty- ing of the pulmonary veins, is a factor of but minor importance. The use of digitalis in mitral insufficiency is familiar to all and the pharmaco- logic action readily explains its usefulness in this connection. Digitalis and its congeners are said to be harm- ful in some cases of mitral stenosis, and they may fail to prove beneficial in insufficiency of the aortic valves. It is suggested that in this condition the blood may gravitate from the brain through the aortic valve during the lengthened diastole. The action of the drugs must be carefully observed in these conditions and they must be withdrawn if they appear to be doing harm. Drugs of the digitalis series are contraindicated in cases of fatty degeneration of the heart, since a heart so weakened could scarcely support the addi- tional burden imposed by the increased arterial tension, nor can hypertrophy be expected to occur in such a heart. They are also contraindicated in 278 PHARMACOPEIA AND PHYSICIAN. all conditions in which an increasing blood pres- sure would be dangerous, for instance, in aneu- rism. With digitoxin particularly, one must constantly watch for the first symptoms of cumulative action, usually gastric disturbance, and it, or other mem- bers of the same group, should be temporarily withdrawn when suggestive symptoms occur. The tincture of digitalis contains a larger pro- portion of the alcohol-soluble digitoxin than does the infusion, in which the digitoxin present is held in solution by means of digitonin. Digitoxin being the most irritant of the known principles of digi- talis, the infusion, containing digitalin principally, will often be preferred. When the heart is weak and irregular digitoxin is probably the most efficient remedy we possess for restoring it to normal contraction. An alcoholic solution of digitoxin may be used to advantage, provided it be well diluted with water when ad- ministered. It is altogether too irritant for hypo- dermic injection, but if the claim made by Cloetta to the effect that he has succeeded in preparing a stable, water-soluble form of digitoxin. which is not very irritant, is substantiated, a distinct advance will have been made in digitalis therapy. The dose of digitoxin as given by the different authors is somewhat variable. Cushny states that 1/12 mg. (1/750 grain) of crystalline digitoxin may be°given three times daily. Schmiedeberg recommends 1/5 mg. (1/330 grain) of the crys- talline digitoxin three times daily. This is the dose used by Marx with good results in Xaunyn’s clinic. The physician will do well not to exceed this latter dose too greatlv. bearing in mind that CIRCULATORY STIMULANTS. 279 cumulative effects may. and sometimes do, develop quite suddenly, even with a dose which has been apparently harmless. Digitoxin and digitalin, pure or in the leaf, are changed into substances with a convulsive action in the presence of moisture, by bacteriologic ac- tion, hence old infusions should not be used nor should such leaves be employed which bear evi- dences of not having been properly dried and care- fully preserved. Digitoxin and digitalin may be kept dissolved in alcohol and diluted as required. The dose of digitalin, or digitalinum verum, is from 2 to 6 mg. (1/30 to 1/10 grain) three times daily. Digitoxin may be prescribed as follows : JDigitoxini (cryst.) gr. 1/12 [005 Alcoholis q. s. ad 3iii 100 1 M. Ft. solutio. Sig. : One teaspoonful in a little water three times a day. Digitalin can be prescribed in the same way but 0.05 is used in place of 0.005 gm. thus : Digitalini veri gr. i 1 05 Alcoholis q. s. ad 3iii 100] M. Ft. solutio. Sig. : One teaspoonful in water three times 1 daily. The tincture of digitalis, diluted with water, is given alone three times a day. Owing to the slow excretion it is not necessary to repeat the dose more frequently, and the drug should be stopped for two days about once a week to avoid cumu- lative effects, whether one of the active principles or a Galenic preparation of digitalis is being used. Sollmann has suggested that strophanthin may deserve an even greater popularity than digitalis, and this suggestion has found support in more re- cent investigations. Strophanthin is now official. 280 PHARMACOPEIA AND PHYSICIAN. whereas the active principles of digitalis have not as yet been included in our Pharmacopeia. Strophanthin causes but little vasoconstriction and it therefore deserves the preference over digi- talis and its principles when increased blood pres- sure is to be avoided. Thus, when dilatation of the heart is due to high blood pressure from in- creased arterial tension, strophanthin may be used, or if digitalis is employed, a vasodilator such as nitroglycerin or one of the nitrites should be given at the same time. Because of its more prompt effect on the heart, strophanthin may be employed to usher in the action when digitalis is to be employed. This promptness of action would also render it prefer- able to digitalis in shock or collapse were it not that the vasoconstrictor action is wanting. Digitalis, or one of its principles, may be given several hours before an operation when there is reason to apprehend shock, so that its action may coincide with the time that shock occurs instead of waiting till that condition has actually developed before giving the slowly acting remedy. Strophanthus seed and the tincture were for- merly of very variable quality, but at the present time they are fairly uniform. Strophanthin. the active principle of strophan- thus seed, is of constant composition, is very solu- ble in water and may, therefore, be dispensed in simple solution. However, it undergoes decompo- sition, in aqueous solutions, and it is, therefore, better to prescribe it in diluted alcohol : 0.01 gm. (1/5 grain) may be directed to be dissolved in 150 c.c. (5 fluidounces) of diluted alcohol and one CIR C ULA TORY 8 TI M l LA N TS. 281 teaspoonful of this solution, diluted with water, given three times a day. Dr. H. C. Wood, Jr., recommends Canadian hemp as a satisfactory and reliable circulatory stimulant, but as his published work appears to have been done with a fluidextract of Apocynum cannabinum and as the Pharmacopeia itself recog- nizes closely allied species of apocynum, that may or may not have similar physiologic properties and therapeutic uses, it may be well to await the re- sults of further investigations before trusting too duplicity in the possible results to be obtained from this drug. Other official members of this group have little to recommend them in preference to the more prominent ones just described. It might be added that the alkaloid of the supra- renal gland is not suited for long continued admin- istration. It does not influence blood pressure when given by the stomach, and but slightly or not at all when injected just beneath the skin. When injected into the muscle there is a transient rise of blood pressure. Its local use has been dis- cussed at greater length in connection with as- tringents (Chapter AC). STRYCHNIN. Strychnin, unlike digitalis, has no preceptible direct action on the heart, but produces its circu- latory effects wholly by its influence on the centers, except in so far as the local action on the alimen- tary canal is concerned ; this may be disregarded in the present consideration of strychnin, which is commonly injected hypodermically when its eir- culatorv effects are desired. 282 PHARMACOPEIA AXD PHY SIC I AX. Therapeutic doses of strychnin cause a rise of blood pressure by stimulation of the vasomotor center ; the reflexes are increased, leading to im- proved tone of the voluntary muscles, and in- creased muscular activity always tends to increase the heart rate; this tendency, however, is counter- acted by the stimulation of the vagus center by strychnin, the heart being slowed or showing little change in frequency. When the slowing is exces- sive there is a fall of blood pressure despite the vasoconstriction, but this does not usually occur. If the tendency to increased frequency predomin- ates over the vagus stimulation the rise of blood pressure is further augmented. As strychnin operates readily to produce its ef- fects it is a most valuable remedy when a quick rise of blood pressure is required. So rapidly are its effects elicited that convulsions may occur in a frog within two minutes of the injection of a toxic dose, and after massive doses rabbits may give a single convulsive leap into the air and be appar- ently lifeless from paralysis of the respiratory and other centers when they strike the operating table. Biberfeld has investigated its mode of action on the respiratory center. He depressed the res- piration by morphin. after which strychnin was injected; this usually resulted in a greater in- crease in volume, (sometimes even exceeding that before the administration of morphin). than in frequency. It has been suggested that morphin depressed the reflex excitability, while strychnin tends to make all reflex efforts maximum. Biberfeld agrees with previous investigators that CIRCULATORY STIMULANTS. 283 strychnin does not cause increased irritability of the center for sensory impulses coming from the lungs, but considers the chemic stimulation of the blood the essential factor. 2 The following preparations are official : Steychnina. — IT. S. — : This is an alkaloid ob- tained from nux vomica; it is also obtainable from other plants of the Loganiaeece. Strychnin is only slightly soluble in water 1/6400, but is soluble in 110 parts of alcohol. Strychnin.® Sulphas. — IT. S. — This is the salt of strychnin that is most extensively used in this country ; it contains five molecules of water and approximately 78 per cent, of strychnin alka- loid. Strychnin sulphate is soluble in 31 parts of water and in 65 parts of alcohol. 2. Owing to the frequency with which poisoning by strych- nin occurs, its toxicology deserves brief mention here. As is well known, strychnin causes a characteristic type of convulsion rather closely resembling tetanus. The amount of the alkaloid that is necessary to produce this toxic effect is much greater, however, than is usually supposed ; but, on the other hand, when once a large amount has actually en- tered the circulation, there is little hope of ultimate recovery. As death is due to paralysis of the' respiratory center life may be prolonged, and a possible recovery brought about, by carrying on artificial respiration. This, however, should be begun before natural respiration ceases or even before' it be- comes very greatly depressed. Strychnin requires several days (3 to 8) for its total elimi- nation. Diuretics hasten elimination and may be of benefit when the amount of the poison that has been taken does not greatly exceed the minimum fatal dose. Cushny advises strong tea (infusion) when the patient is seen with the strychnin in the stomach. This advice seems to be based on a misconception of the capacity of tea tannin for forming the insoluble tannate. The fact that strychnin acts directly by paralyzing the re- spiratory center fully explains the possible danger that may result from the use of a stomach tube, and it will not be nec- essary to repeat this frequent caution. 284 PHARMACOPEIA AND PHYSICIAN. On the continent of Europe the preference is Usually accorded to the nitrate. This is official in our Pharmacopeia as : Strychnine Nitras. — U. S. — This represents 84 per cent, of strychnin alkaloid and is soluble in '42 parts of water or in 120 parts of alcohol. The average dose of either of the official prep- arations is given as 0.001 gm. (1 mg. or 1/64 gr.). Strychnin is useful in all forms of low blood pressure because of its action on the vasomotor center. There can be little doubt of the beneficial ef- fects of strychnin in many cases of shock or col- lapse, but when irrecoverable shock exists it ap- pears to depress further the centers after an ex- tremely brief stimulation. 3 To secure its greatest usefulness in conditions of this kind strychnin should be given hypodermic- ally, or to secure an even quicker action it should be injected deeply into the muscle of the arm or thigh. This method of hypodermic injection is usually to be preferred as it is le-s painful than in- jections just beneath the skin. Strychnin is one of the best respiratory stimu- lants and in an emergency large doses may be given. It is always to be remembered that strych- nin is a remedy for the crisis and is not to be 3. Crile defines surgical shock as an exhaustion of the vasomotor centers, the cardiac and respiratory centers being only secondarily involved, and collapse as due to a suspen- sion of the functions of the cardiac or vasomotor centers or to hemorrhage. Of course, an exhausted or paralyzed structure can not be stimulated. Sollmann defines both shock and collapse as a sudden depression of the activity of the medullary center ; if of reflex origin, shock : if direct, collapse. We employ the terms in the latter sense. A depressed center may be stimulated. CIRCULATORY STIMULANTS. 285 used as digitalis is, to maintain blood pressure for a considerable length of time. When paralysis of the limbs is due to a lesion in the cord which completely blocks the transmis- sion of nerve impulses strychnin can do no good, since it has no peripheral action, but if the paraly- sis results from a lesion in the brain the increased reflexes which strychnin causes will serve to delay muscular atrophy. It may also serve to restore the tone of the reflexes when these are lowered by functional disturbances of the cord. Thus incon- tinence of feces and urine may be relieved when these are due to the lowered reflex centers for the sphincters of the bladder and anus. Caffein is closely related to staychnin, to which, however, it is greatly inferior, so far as any in- fluence on the circulation is concerned. It stimu- lates the vasomotor and respiratory centers and is useful, therefore, in the treatment of poisoning by morphin and other narcotics, in the form of strong tea, but strychnin serves the same purpose and more efficiently. Hoffmann noticed that theobromin possessed a stimulant action on the myocardium, similar to that shown by caffein, but no vasoconstrictor effect. In therapeutic doses of either agent, however, this cardiac effect is of little importance. ATROPIN. Atropin causes acceleration of the heart by par- alyzing the vagus endings, and this also causes an increased systole and a lessened diastole. The rate of the heart may be twice as great as under normal conditions, the result being a considerable •280 PHARMACOPEIA AND PHYSICIAN. increase in the output of the heart in a unit of time. The effect on the circulation of the increased heart action is supplemented by the constriction of the arterioles of the splanchnic area, due to stimulation of the vasoconstrictor center by atro- pin, which also stimulates the vasodilator center for the vessels of the skin, particularly those of the face and neck, but this is of comparative^ little influence on the general blood pressure which rises in response to the two actions just mentioned. The influence of atropin on the heart rate is much less in children and in old age than it is be- tween the ages of 20 and 60 years, because the vagus inhibition is slight at the extremes of life in man. The vagus is much more active in some animals than in others. In this respect the dog re- sembles man. Atropin majf cause a brief but unimportant slowing of the heart, due to stimulation of the cen- ter. preceding the acceleration which depends on the paralysis of the vagus endings. While it has been undeniably shown that atropin may power- fully stimulate the myocardium, this effect with therapeutic doses is so slight that it may be en- tirely disregarded. Atropin acts as a stimulant to the respiratory center, but it is inferior in this re- >pect to strychnin ; it increases the rate, and prob- ably the depth, of the respiration. The central action of atropin is exerted mainly on the motor area, but it has been suggested that the differences between the action of atropin, caffein and strychnin on the various parts of the central nervous system are in degree rather than in kind. Thus, while caffein acts mainly on the CIRCULATORY STIMULANTS. 287 higher centers in man, stimulating the psychic functions, it is capable of causing strychnin-like convulsions in the frog. All three act as powerful respiratory stimulants in mammals. Atropin is official as : Atropina. — U. S. — Atropin is an alkaloid pre- pared from Air o pa Belladonna , or from other plants of the same family. It is soluble in 450 parts of water and in less than 2 parts of alcohol. Atropine Sulphas. — U. S. — This salt of atro- pin is official in many if not all pharmacopeias and is the best known and most widely used prep- aration of the atropin group. It is soluble in less than one part of water and in 4 parts of alcohol. Average Dose: (Alkaloid or salt) 0.0004 gm. (0.4 or 1/160 gr.). Atropin is indicated when the heart is consider- ably slowed. For this purpose the average dose given above is not usually sufficient, about 1 mg. (1/65 grain) being necessary to increase the rate; so large a dose being necessary to produce paralysis of the vagus endings in the heart. If must be remembered, however, that in children and in the very old (after 70) the effect to be expected is much less than that seen between the ages of 20 and 60. This larger dose causes stoppage, or, at least, a marked diminution of salivary secretion with consequent dryness of the mouth and throat. While atropin has been used in shock and col- lapse, it can have but little influence on blood pres- sure or respiration in such cases. Atropin may be used to determine Avhether an abnormally slowed or intermittent heart results from central influences or from causes within the heart itself, since it cuts off all impulses from the center arriving through 288 PHARMACOPEIA AND PHYSICIAN. the vagus, but produces no appreciable effect if the cause lies within the heart. Atropin has been used to prevent the reflex stop- page of the heart occurring at the commencement of anesthesia, but it has been shown that there is no danger of such a catastrophe if the anesthetic is not used in too great concentration. Poisoning by certain fungi which contain mus- carin, while rare, may best be treated with moder- ate doses of atropin. Pilocarpin is also antag- onized in nearly all its actions by atropin, but the latter does not counteract the cardiac effects of phvsostigmin which acts on the myocardium. The value of atropin in opium poisoning has been much disputed. It seems to possess no ad- vantage over caffein and strychnin in such cases and it has the disadvantage of adding to the de- pression of the respiratory center if more than a small dose is given. Clinical experience seems to have abundantly proved that small doses of atro- pin are corrective for ordinary doses of morphin, and it is almost universally so used . 4 Atropin is usually given hypodermically when the central effects are desired. CAMPHOK. Camphora. — U. S. — Camphor is a white, vola- tile, solid substance having a crystalline structure and a characteristic aromatic odor and taste. Cam- phor has been used in the Far East for many cen- turies, but was not known in Europe until intro- 4. A widely used combination consists of morphin sul- phate 0.015- gm. ( J 4 grain) and atropin sulphate 0.0004 gm. (1/160 grain) prepared in the form of the now popular hy- podermic tablets or dissolved in distilled water sufficient for one dose. CIRCULATORY STIMULANTS. 289 duced by the Arabians. It is now official in all pharmacopeias. Average Dose: 0.12 gm. (2 grains). Aqua Camphors. — TJ. S. — This is a saturated solution of camphor in distilled water. It is fre- quently used as a vehicle for other medical sub- stances. Average Dose: 1 c.c. (2 fluidrams). Spiritus Camphors. — U. S. — This is a 10 per cent, solution of camphor in alcohol. Average Dose: 1 c.c. (15 minims). Linimentum Camphors. — U. S. — This prep- aration, variously known as camphor liniment and camphorated oil, contains 20 per cent, of camphor dissolved in cottonseed oil. While largely used as a mildly rubefacient local application it is not in- frequently used for hypodermic injections or for the internal administration of camphor in the form of an emulsion. The average dose would be about half of that given under spirit of camphor. In shock or collapse camphor is given by the stomach, producing a feeling of warmth and prob- ably acting reflexly for the most part. The respir- atory and vasomotor centers, as well as the heart muscle, are stimulated, thus causing a rise of blood pressure. The heart is usually slowed and the contraction strengthened. Camphor is almost insoluble in water and only slightly volatile at the body temperature, and its action, therefore, is very uncertain; 0.03 gm. (!4 grain) may improve the pulse in some cases while twenty times as much may he required in others, hence but little reliance can be placed on it in crises, though it is very often effective. The spirit, diluted with water, is fre- quentlv used for internal administration. A num- 290 PHARMACOPEIA A XL) PHYSICIAA. ber of camphor derivatives have been employed from time to time, but they have not been shown to possess any advantages over camphor itself, or one of its more simple preparations. Camphor is frequently employed as a diapho- retic, particularly in combination with other agents, because of its stimulation of the vasodila- tor centers for the cutaneous vessels. As noted above, camphor water alone has little therapeutic value and is useful mainly as a vehicle for other substances. Camphor may be given in pill form, in capsules or in the form of an emul- sion. Probably the best method of administering camphor consists in suspending the finely pow- dered substance in twenty parts or more of milk. For this purpose from twenty drops to one tea- spoonful of the spirit of camphor may be directed to be given in one or two tablespoonfuls of milk. The several preparations of camphor are com- monly employed externally as a mild rubefacient, but the action of camphor when applied in this way is largely, if not entirely, a local one. MUSK. Moschus. — U. S. — This substance has been used in Europe for several centuries, and in China and other far Eastern countries from time im- memorial. The poi’tion that is now official is de- scribed a? •'‘The secretion from the preputial fol- licles of ]\[oschus moschiferus” (musk deer), an animal which inhabits Thibet and other parts of Central Asia. Average Dose: 0.25 gm. (4 grains). Tinctura Moschi. — IT. S. — This represents 5 per cent, of musk in diluted alcohol. CIRCULATORY STIM ULANTS. 291 Average Dose: 1 c.c. (15 minims). Musk was brought forward nearly a century ago as a powerful circulatory stimulant, and S. Solis- Cohen recently recommended it as an efficient and dependable remedy when it can be obtained of good quality, but it is extremely expensive and subject to gross adulteration. Musk probably resembles camphor in its action on the centers and has the advantage of greater solubility in proportion to the amount required. Castor fiber and sumbul root, which have been recommended as substitutes for musk, are entirely devoid of any such central action as that claimed for the latter. Musk may be given in capsules, or in some cases the tincture may be preferred. AMMONIUM PREPARATIONS. While ammonia, as one of the products of the decomposition of nitrogenous materials, was known from a very early period, the volatile salts of this substance were not available in Europe as medi- cines until after the thirteenth century, when Ray- mundus Lulius first produced ammonium carbon- ate from urine. The stimulating action of this salt, it is said, was known for many centuries to the Hindoos, and was probably known to the Arabians. It is now official as: Ammonii Carbonas.— U. S.— This is a white, hard, translucent solid having the characteristic odor of ammonia and a sharp saline taste. The official salt is described as being “a mixture of acid ammonium carbonate and ammonium car- bamate.” Average Dose: 0.25 gm. (4 grains). Aqua Ammoni.e. — IT. S. — This is an aqueous 292 PHARMACOPEIA AMD PHYSICIAX. solution of ammonia containing 10 per cent., by weight, of gaseous ammonia. Average Dose: 1 c.c. (15 minims). Spikitus Ammonite Aromaticus. — U. S. — This is a hydroalcoholic solution containing 3.4 per cent, of ammonium carbonate, 9 per cent, of ammonia water and 70 per cent, of alcohol aroma- tized with oil of lemon, oil of lavender flowers, and oil of nutmeg. Average Dose: 2 c.c. (30 minims). The volatile salts of ammonium, in the form of the well-known “smelling salts,” are very com- monly employed by inhalation for their reflex ef- fects on the respiratory and cardiac centers. The aromatic spirit of ammonia when taken by the stomach has a similar action. Other actions of am- monium salts have been enumerated in previous chapters. The water of ammonia, when taken internally, merely acts as a caustic alkali. It is seldom so used. The aromatic spirit is usually added to water at the moment of taking. Smelling salts consist of varying mixtures of ammonium carbonate, or of ammonium chlorid with potassium carbonate, and spirit of ammonia, to which oil of lavender flowers is usually added as an aromatic. ALCOHOL AND DERIVATIVES. Alcohol, or distilled spirit, was probably intro- duced into Europe by the Arabians in the 10th or 11th century. 5 Apart from the several forms of alcohol that are official we have : 5. According to Pereira the Arabians obtained their knowl- edge of distilled spirit from the Chinese, who knew and used distilled spirit at a much earlier period. CIRCULATORY STIMULANTS. 293 Spiritus Frumenti. — L T . S.- — An alcoholic liquid obtained by the distillation of the mash of fermented grain, such as Indian corn, rye, wheat and barley, or their mixtures. To conform with the official requirements whisky should be at least four years old and comply with a number of phy- sical requirements and chemical tests that are now provided. Spiritus Vint Gallici. — U. S. — Brandy. This is an alcoholic liquid obtained by the distillation of the fermented unmodified juice of fresh grapes. Like whisky it should be at least four years old and should conform to the tests for identity and purity that are described in the Pharmacopeia. iP.TiiER.- — TJ. S. — Ether or ethyl oxid was dis- covered by Valerius Corclus, about 1540, and de- scribed as “Oleum vitrioli dulci.” The prepara- tion appears to have been entirely forgotten and was rediscovered by Frobenius, a London apoth- ecary, about 1730. Sulphuric ether, the name given it at that time,, although long known to be a misnomer, is still re- tained in connection with commercial varieties of the substance. Average Dose: 1 c.c. (15 minims). Spiritus aEtheris. — U. S. — This contains 32.5 parts of ether and 67.5 parts of alcohol. Average Dose: 4 c.c. (1 fluidram). Spiritus JEtheris Compositus. — U. S. — This preparation, more popularly known as Hoffmann’s anodyne, contains 2.5 per cent, of ethereal oil, in addition to the ether. It has no evident advantages over the simple spirit of ether and may be given in the same dose. Alcohol in the form of whisky or brandy is 294 PHARMACOPEIA AND PHYSIC I AX. much used in shock or collapse in connection with other agents such as strychnin and digitalis. Its value is strongly asserted by some authorities and disputed by others. Ordinary doses of alcohol have little effect on the circulation in animals, but clinical evidence seems to prove that alcohol does possess some value in the conditions mentioned, particularly when a very brief respite for the heart tides over a crisis. Spirit of ether may he given by the stomach, or used by hypodermic injection, and probably acts reflexly on the centers in such cases. ERGOT. Ergot has been recommended in shock and in hemorrhage in inaccessible locations. The use in the latter condition is based on its undoubted power of causing vasoconstriction in certain areas. It is much less useful than strychnin in shock be- cause of its slow action, and in hemorrhage there is no reason to expect a greater vasoconstriction at the bleeding point than elsewhere and a rise in the general blood pressure beyond that necessary to sustain the circulation in the medulla, is contra- indicated in hemorrhage. This, of course, does not apply to postpartum hemorrhage, because er- got has a specific action on the uterus, causing a firm contraction and thereby closing the bleeding vessels by compression. Sollmann and Brown have recently studied the action of ergot when injected intravenously into dogs . 6 They found that it influenced the general circulation but little, particularly when the blood pressure was much lowered, and that it caused a 6. The Journal A. M. A., July 22. 1905, p. 229. CIRCULATORY STIMULANTS. 295 temporary fall in the blood pressure with speedy recovery, generally followed by an unimportant rise. The effects were mainly due to the action of the heart, as the vasomotor action was very slight. The further discussion of its obstetrical use does not belong here. Ergota. — U. S. — The sclerotium of Claviceps purpurea, gathered from rye, and not more than one year old. While ergot has been used in Germany for cen- turies as a household remedy, it was not generally recognized as an efficient drug until some time after 1777, when Desgranges published several es- says on the use of ergot. The vasoconstrictor properties of this drug ap- pear to be due to the alkaloid cornutin, discovered by Kobert in 1884, and more fully described by Keller in 1894. Extractum Ergots. — U. S. — This is a hydro- alcoholic extract of ergot partially purified by the addition of hydrochloric acid subsequently neutral- ized with sodium carbonate. It should represent eight times its weight of ergot. Average Dose: 0.25 gm. (4 grains). Fltjidextractum Ergots. — IT. S. — This is di- rected to be made with diluted alcohol that has been acidified by the addition of acetic acid. Average Dose: 2 c.c. (30 minims). Vinum Ergots. — IT. S. — This represents 20 per cent, of the fluid extract of ergot in fortified white wine. Average Dose: 8 c.c. (2 fluidrams). Ergot is preferably given in the form of the fluidextract without other additions. There are 296 PHARMACOPEIA AND PHYSICIAN. a number of water-soluble preparations on the market at the present time that are intended for hypodermic use, which, it is claimed, possess all the active principles of ergot, without the odorous and nauseating constituents. CHAPTER XII. CIRCULATORY DEPRESSANTS. The circulation may be depressed by acting on those structures the stimulation of which causes an increase in blood pressure. Hence we might divide these agents into two groups: 1. Those acting on the heart mainly, directly or through the centers. 2. Those acting for the most part on the vessels, directly or indirectly. An agent which slows the heart without caus- ing a compensating increase in the strength or the amplitude of the contraction, or a constriction of the vessels, must cause a fall in the arterial pres- sure, as will he readily understood by reference to what has previously been said in regard to acceler- ation of the heart causing a rise in pressure. Here, too, we have in every case a combination of effects, and the resulting change in the circulation must depend on the predominance of one or another. As a matter of fact, we have no circulatory depres- sant which is used therapeutically to slow the heart by direct action on the myocardium, but there are a number which induce slowing by in- direct action. ACONITE. Therapeutic doses of aconite cause slowing of the heart by stimulating the vagus center, with- out materially affecting the strength of the in- dividual contractions or the condition of the vaso- motor center. The result, therefore, is a fall in arterial pressure. 298 PHARMACOPEIA AND PHYSICIAN. The lessened cardiac action is accompanied by a decline in the temperature, whether this was pre- viously normal or that of fever. The effect is commonly ascribed to the change in the circula- tion, but it has not been proved that the heat regulating center is not involved in the action. It will be noticed that the effects of digitalis and aconite on the circulation are diametrically opposed, except for the slowing of the pulse rate, which both induce. Toxic doses of aconite act directly on the heart, causing acceleration with diminished force of con- traction. In mammals the acceleration is pre- vented for a time by the vagus stimulation, and the heart is actually slowed, but in reality only a therapeutic dose has been absorbed in the early stage of the action; this stimulation rapidly gives place to depression and then to paralysis of the center, the acceleration becoming marked and be- ing soon followed by great irregularity. Delirium cordis occurs before the heart stops in diastole. Paralysis of the respiratory center is usually the immediate cause of death, hence atropin is capable of saving a certain percentage of animals experi- mentally poisoned with a barely fatal dose of acon- ite. If an excessive dose has been taken even ar- tificial respiration will prolong life only for a short time, as the heart soon becomes paralyzed after the phenomena enumerated above. Despite the fact that it was well known and long in use as a poison, particularly for wild ani- mals, aconite is a comparatively recent addition to our materia medica, having been introduced by an Austrian physician, Storek. about 1762. Aconitum. — U. S. — This is the dried tuberous CIRCULATORY DEPRESSAXTS. 299 root of Aconitum napellus, collected in autumn. When assayed by the process given in the Phar- macopeia it yields not less than 0.5 per cent, of aconitin. Average Dose: 0.05 gm. (1 grain). The official preparations of aconite are as fol- lows : Fluidextractum Aconite — U. S. — This is made with a mixture of 75 parts of alcohol and 25 parts of water and should contain 0.4 per cent, of aconitin. Average Dose: 0.05 c.c. (1 minim). Tinctura Aconiti. — U. S. — This preparation has been materially reduced in strength and now represents 10 per cent, of the crude drug, or ap- proximately one-third of the strength of the tinc- ture that was official in the Pharmacopeia for 1890. It may be added that the change was made in conformity with the recommendations of the inter- national conference for the unification of formulas of potent medicaments and that, in addition to be- ing in harmony with this international standard it will be foimd to be more uniformly active than the stronger but more variable tincture official in the earlier pharmacopeias. Average Dose: 0.6 c.c. (10 minims). Aconitina.- — II. S. — This is an alkaloid ob- tained from aconite. It is the most active and most potent substance in the Pharmacopeia. The acon- itin now official is the crystalline alkaloid and should not be confounded with the amorphous substance formerly official or the comparatively weak eclectic preparation of aconite. 300 PHARMACOPEIA AND PHYSICIAN. Average Dose: 0.00015 gm. (0.15 mg. or 1/400 grain). Aconite finds its greatest usefulness in cases of high blood pressure with a strong, rapid heart, par- ticularly in fever in robust persons. It then simply slows the heart, lessening its output and causing a fall in temperature and in arterial tension. Fever alone is not an indication in every case for the use of aconite. In continued fevers and in any case in which the heart is feeble or the arterial tension low from any cause (even though the pulse may be rapid), aconite is contraindicated. Since the antipyretic benzene derivatives have come into general use the employment of aconite in fever has correspondingly declined, but we have seen that the synthetic antipyretics are far from being the harmless substances that the manufac- turers would have us believe, and aconite deserves to be used more frequentty in suitable cases of fever. “Colds” are troublesome forms of congestion re- sulting from circulatory disturbances which are often relieved by repeated small doses of aconite. For this purpose 3 drops (about 1 minim) of the tincture of aconite of the present Pharmacopeia, which would be equivalent to about 1 drop (1/3 minim) of the tincture official in the Pharma- copeia, 1890, well diluted with water, may be given every fifteen minutes for two hours, then hourly until relief is obtained. Aconitin is so intensely irritant that it is not suitable for use without great dilution, and as there is’ some chance of confusing the much more po- tent article now official with the eclectic or the CIRCULATORY DEPRESSANTS. 301 amorphous preparations, it will be found prefer- able to use the tincture of aconite in nearly every case, more particularly since this is now required to be of a definite aconitin strength. Because of its irritant action aconitin is not adapted for hy- podermic use, but it may be given, largely diluted with water, as follows : R. Aconitin (crystalline) gr. 1/16 1 004 Alcoholis 3iv 15 1 Aquse q. s. ad §iv 120 1 Sig. : A teaspoonful may be taken every three hours. The disadvantage, not to say danger, of trying to weigh such small amounts is apparent, and serves to further illustrate the advantage of using the tincture. The tincture is usually given alone, except for the water used in diluting it. VERATRUM. Yeratrum rather closely resembles aconite in its therapeutic action, and it was widely used at one time for the reduction of fever. The extent of its use was largely due to its popularization in the form of Norwood’s Tincture of A 7 eratrum, but it seems to possess no advantage over aconite, and it is now but seldom used internally. Yeratrum. — IT. S. (Yeratrum Viride. — IT. S. P., 1890) — Under the single heading veratrum the Pharmacopeia now recognizes the dried rhi- zome of Veratrum viride or of Veratrum album. While it is true that there is no marked difference between the two drugs some physicians prefer the American root and therefore should specify “Yera- trum viride, U. S. P., 1890.” Average Dose: 0.12 gnu (2 grains). 302 PHARMACOPEIA AND PHYSICIAN. The official preparations are: Fltjidextractum Veratki. — IT. S. — This is di- rected to be made with alcohol. Average Dose: 0.1 c.c. (1 y 2 minims). Tinctura Yeraxri. — U. S. — This preparation represents 10 per cent, of the crude drug in alco- hol and is practically one-fourth the strength of the corresponding preparation in the Pharmacopeia for 1890. Average Dose: 1.0 cc. (15 minims). Veratrina. — U. S. — This is a mixture of alka- loids obtained from the seeds of Asagrcea officinalis. Veratrin should not be confounded with the eclec- tic preparation of the same name. Average Dose: 0.002 gm. (1/30 grain. THE NITRITES. The nitrites, organic as well as inorganic, lower the blood pressure by causing vasodilation. Thera- peutic doses exert but little influence directly on the heart. It has been shown that the nitrites act on the muscles and nerve endings of the arterioles, and that even the veins undergo dilatation. Any considerable dilatation of the arterioles and veins of the splanchnic area must inevitably lead to a decline in the general arterial pressure, regardless of the action on the heart. In man the heart actually does show acceleration in the first stage of the action with amyl nitrite because of the depression of the vagus center; the blood pressure remains high and the vasodilation affects the face and neck, because of depression of the vasoconstrictor centers for those areas; but as the dilatation extends to the splanchnic and other areas the general arterial pressure falls. CIRGULA TOR Y DEPRESSANTS. 303 There has been some diversity of opinion in re- gard to the effect of amyl nitrite on the cerebral circulation. Leonard Hill agrees with those who believe that there are no nerves controlling the di- ameter of the cerebral arteries, and he declares that the arterial pressure in the brain simply fol- lows that in the carotids. Wiggers has found that adrenalin constricts the cerebral vessels and we have Elliott’s dictum, based on his masterly re- search, that the constrictor effect of adrenalin on vessels is proof of sympathetic nervous control. Brodie and Dixon also found that the action of adrenalin is exerted on nervous elements. Should Wiggers’ results be confirmed there would be little reason to doubt that the nitrites do affect the cali- ber of the cerebral vessels. The nitrites are capable of causing some dilata- tion of the vessels in excised nruscles when the nerve endings are not concerned ; hence they must also act on the muscular elements of the vessels to some extent. The nitrites produce methemogiobin in the blood, but do not cause the destruction of' the cor- puscles, as other methemogiobin formers do, and in man this does not arrest oxidation completely, because the tissues reduce methemogiobin slowly. This is not an important factor, however, with the therapeutic doses of the nitrites. 0. Loeb suggested as a possible explanation of the value of amyl nitrite in angina pectoris that the coronary vessels, like those of the face and brain, may be dilated at first, before the action on the general circulation begins. Filelme showed that the therapeutic dose of amyl nitrite caused vasodilatation by central action, and Loeb found 304 PHARMACOPEIA AND PHYSICIAN. it did not affect the vessel tonus independently ex- cept when in such concentration as to prove poison- ous. Small doses were found to have no constant effect on the vessels of the coronary circulation in the excised heart. Amyl nitrite acts very rapidly when inhaled, but the action is over in about twenty minutes. The effects of glyceryl trinitrate or nitrogly- cerin are much more slowly induced and they per- sist for some hours. Sodium nitrate is decomposed by the hydrochloric acid of the gastric juice, thus giving rise to irritation of the stomach. Glyceryl trinitrate is not decomposed in the stomach, but it has the disadvantage of often causing headache. In some cases this action does not occur after the drug has been used for some time. Glyceryl trini- trate is decomposed in the blood, with the libera- tion of the nitrous acid radicle, hence it acts like the nitrites. Spieitus Glycerylis Nitratis. — U. S. (Spiritus Gloyoini. — IJ. S. P., 1890) — Com- monly, though incorrectly, termed nitroglycerin, is an alcoholic solution containing 1 per cent, by weight of glyceryl trinitrate. Average Dose: 0.05 c.c. (1 minim). Amylis Nitris. — U. S. — This is a liquid con- taining about 80 per cent, of amyl nitrite. Average Dose: 0.2 c.c. (3 minims). Sodii Nitris. — U. S. — This usually occurs in white, or nearly white, fused masses, soluble in less than two parts of water. The salt deliquesces on exposure to air and is also gradually oxidized to sodium nitrate and thus becomes unfit for use. Average Dose: 0.06 gm. (1 grain). CIRCULATORY DEPRESSANTS. 305 The nitrites, and glyceryl trinitrate, are of prime importance in the depression of the circula- tion and may be used when it is deemed necessary to lower the blood pressure, for example, when a weakened heart is becoming- exhausted by contract- ing against a great arterial resistance, and the con- tractions are incomplete, as in arteriosclerosis. A slight lowering of the aortic resistance often en- ables the heart to contract more perfectly while a coronary vasodilation secures a better nutrition of the heart. This group is contraindicated, however, when the blood pressure is already low (however weak and rapid the heart may be), because a certain de- gree of arterial tension is absolutely essential for maintaining the coronary and medullary circula- tions. Amyl nitrite is to be preferred when a speedy action is desired, as in acute attacks of angina pec- toris. When the constriction of the vessels is of spasmodic origin the nitrites usually give relief, but in the later stages of arteriosclerosis, when most of the muscular tissue has been replaced by fibrous, thus narrowing the lumen of the vessels, it is obvious that such vessels can not be caused to dilate by any means. It must not be forgotten that while relief is often obtained in the acute attacks of the early stages of angina pectoris, the nitrites are merely palliative and in no sense curative. The nitrites, and more particularly amyl nitrite, are indicated in vasomotor spasm occurring in any disease, un- less specifically contraindicated by other condi- tions. The action of amyl nitrite is very speedily eli- 30G PHARMACOPEIA AND PHYSICIAN. cited when it is inhaled, but when spasm of the respiratory muscles interferes with the inhalation it may be injected into the deep muscles of the thigh. Spirit of glyceryl trinitrate is to be preferred in chronic conditions of abnormally high blood pres- sure, because of its more protracted action. One minim is given three times a day, or the dose is increased till effective. It may be injected hypo- dermically or given by the stomach, as it passes through that organ unchanged, and, therefore, causes no such disturbances as are seen with so- dium nitrite. While this substance is usually considered as be- ing extremely poisonous, it is said that more than 12 c.c. (3 fluidrams) have been given in the course of a day with no bad effects. Aqueous solutions of glyceryl trinitrate are unstable and are fre- quently quite worthless. The spirit sometimes gives almost immediate relief in headache, when this is attended with high blood pressure, but, on the other hand, it may increase the headache if the blood pressure is low. As is well known the head- ache which glyceryl trinitrate commonly causes is one of the greatest objections to its use. The nitrites, and particularly the spirit of glyceryl trinitrate, may be used to counteract the vasoconstrictor effect of digitalis or strychnin when the action is undesired. Because of its ready decomposition spirit of nitrous ether does not yield enough of the nitrous acid radicle to exert any therapeutic action on the circulation. The action of the spirit is exerted re- flexlv as in the case of alcohol and ether. The spirit of nitroglycerin may be given in CIRCULATORY DEPRESS AX TS. 307 simple solution in order to avoid the measuring of such small doses as one minim. It may be pre- scribed as folows : R. Spiritus nitroglycerini m. xv 1| Aqu* gii 60| The dose of this solution is a teaspoonful. Large amounts should not be prescribed or dispensed. The following illustrates the method of prescrib- ing sodium nitrate: R. Sodii nitritis gr. xv 1| Aquae (recently boiled) §ii 601 This solution should he kept well corked. The dose is one teaspoonful. The well-Jvnown “pearls” of amyl nitrite afford the most convenient form for dispensing that sub- stance; they must be kept cool to avoid loss by breakage, and when used, one is crushed in a hand- kerchief and the contents inhaled by the patient at once. Bloodletting was formerly in vogue as a routine procedure when it was desired to reduce the blood pressure, but in healthy animals the vasomotor center exercises such perfect control over the blood pressure that the loss of blood produces very little lasting effect unless it is so great as to cause col- lapse symptoms. While the loss of a moderate amount of blood is well borne by robust patients, and in some cases may even prove beneficial, acon- ite and the nitrites are nearly always to be pre- ferred as temporary measures, while the control of the diet (including liquids) and the use of saline purgatives will serve to diminish the amount of blood for a longer time in suitable cases. Hydrated chloral is one of the most effective 308 PHARMACOPEIA AND PHYSICIAN. agents in onr possession for lowering the blood pressure by depressing the vasomotor centers and while this action is much employed in laboratory experiments, it is not elicited in man by perfectly safe doses such as are used to induce sleep. CHAPTER XIII. DIURETICS AXD DIAPHORETICS. Diuretics and diaphoretics may be considered together since they are often used for the same purpose, the one being used to supplement the other, and because the same agent which produces diuresis under certain conditions, may cause dia- phoresis when these conditions are slightly changed. Diuretics may be divided broadly into those which influence the circulation, and those which act on the secretory cells of the kidney. Though the same agent may possess both actions to some extent, Ave shall consider these remedies with ref- erence . to the principal effect according to this classification. While the exact mechanism of urinary secretion remains a problem, the indications for diuresis and the method of causing it are fairly clear. When the official remedies all fail to produce this effect we may usually attribute the failure to the condition of the kidney, feeling sure that the secre- tory cells are incapable of performing their func- tion and that nothing short of the creation of new cells can be effective. Even this task is not beyond the powers of some of the much vaunted mineral waters and nostrums if we are to believe the state- ments made in the circulars and other advertise- ments of the proprietors. 310 PHARMACOPEIA AND PHYSICIAN. Diuretics are especially indicated in dropsy of cardiac, or even of renal, origin, provided the cells are capable of free secretion. In renal dropsy agents of the first class (those which influence the circu- lation), or those which mildly stimulate the kid- ney cells without producing irritation, are to he preferred. If the renal cells are incapable of in- creased secretion, diaphoresis should be resorted to in order to give rest to the kidneys. Diuretics are also important in causing the re- moval of toxins and substances which form con- cretions (urates and phosphates). DIGITALIS. Nearly all authorities agree that digitalis is the most important of the official remedies in the treatment of dropsy of cardiac origin, its action being directed mainly toward the increase in the efficiency of the heart, with a consequently im- proved circulation in the kidney and increased diuresis. For this purpose the tincture is fre- quently employed, but, perhaps, the most efficient remedy is the combination of digitalis with squill and calomel, commonly called Niemeyer’s pills . 1 The official squill is too irritant to permit of its employment in nephritis. This is very important and should be borne in mind if one uses any of the 1. The formula for this pill is as follows : R. Pulvis digitalis Pulvis scilla\ aa grs. x | GO Hydra rg. chloridi mit grs. i % | OS This amount is to he divided into ten pills, or preferably, capsules. One of these pills every three hours will be found effective. The calomel is often omitted, or it may be re- placed by 0.06 .g. m. (1 grain) of the blue mass (massa hydrargyri) in each dose, if it is to be made into pills, or gray powder (hydrargyrum cum creta), if into capsules. DIURETICS -USD DIAPHORETICS. 311 much-heralcled diuretic nostrums which contain squill or its active principles. That squill is extremely active in causing a watery diuresis is true, but in overdoses it is equally potent to lessen or even to suppress the flow by reason of its irritant action. This may result in bloody urine. The dose of squill, in powder, is 0.05 to 0.1 gm. (one or two grains) every three hours until some nausea occurs. Rather closely resembling digitalis in its action on the heart and as a diuretic, if indeed, it may not surpass the older drug in the latter case, is strophanthus, which does not cause the same de- gree of vasoconstriction which sometimes interferes with or prevents the diuretic action of digitalis. It is mostly used in the form of the tincture. While strophanthus has some advantages, such as the more prompt action and a slighter tendency to cause cumulative effects, clinicians have not found it so generally useful as digitalis. The powerful action of strophanthin as a local anesthetic, though denied, has been well estab- lished. Apocynum has enjoyed a considerable reputation in domestic practice as a remedy in dropsy, but appears to be inferior to digitalis in the same group with which it belongs. Digitalis, strophanthus and apocynum and other preparations have been considered in Chapter XI. CAFEEIN. When cardiac stimulants or other agents cause such vasoconstriction as greatly to lessen the 312 PHARMACOPEIA AXD PHYSICIAX. amount of blood which passes through the kidney, and consequently the diuresis, a vasodilator is sometimes employed, but it is more rational to avoid the necessity for this when possible. When the object of diuresis is to get rid of fluid which has accumulated, it is, of course, better to avoid unnecessary amounts of water, and in such cases diuretics are given in solid, or at least con- centrated, form. Caffein is the most prominent of the official drugs which produce diuresis mainly by action on the kidney cells. While digitalis may act slightly on the kidney cells, but mainly on the heart, caffein, on the other hand, acts mainly on the cells of the kidney and much less on the heart. It may, however, cause such considerable vasoconstriction as seriously to lessen the amount of blood passing through the kidney and the diuresis in conse- quence, in that case the unofficial theobromin might be employed, as this is said to interfere much less with the circulation. Dr. G. 1ST. Stewart states that caffein causes a passing vasoconstriction in the kidneys with lessened diuresis, soon followed by vasodilation with increased diuresis. When cerebral excitement (a tendency to wake- fulness) is to be avoided, caffein is contraindi- cated. Caffein is a constituent of tea, coffee, kola, and more abundantly (5 per cent.), of guarana, which is official. Caffein is not very soluble in water or alcohol, but its solubility in water is greatly increased by such salts as potassium bromid, and sodium ben- zoate or salicylate; this well-known fact has been DIURETICS AND DIAPHORETICS. 313 appropriated as a "discovery” by manufacturers of certain nostrums. 2 Caffeina. — U. S. — This is a feebly basic (alka- loidal) substance obtained from Thea sinensis, Coffea arabica or other plants. It does not form stable salts. Average Dose: 0.05 gm. (50 mg. or 1 grain) . Two other soluble forms of caffein are: Caffeina Citrata. — U. S. — This consists of equal parts of caffein and citric acid. Average Dose: 0.1 gm. (2 grains). Caffeina Citrata Effervescent. — II. S. — This contains 4 per cent, of citrated caffein. Average Dose: 4 gm. (60 grains). Diuretin is a mixture of theobromin-sodium and sodium salicylate, while agurin consists of theo- bromin-sodium and sodium acetate. Diuretin is decomposed on exposure to the air and becomes much less soluble. When caffein or other diuretics produce a more than temporary vasoconstriction in the kidney, one drop of the 1 per cent, solution of nitroglycerin may be given at the same time. The usefulness of hot tea as a diuretic is too well known to require further comment. 2. The following mixture, to be varied according to needs, represents the method of using caffein in this soluble form : Caffein (alkaloid) | Sodium salicylate, each 3i 4| Cinnamon water to make oiii 100 1 Each teaspoonful contains about 0.2 gm. (3 grains) of caffein. Sodium benzoate or lithium salicylate or benzoate may be substituted for the sodium salicylate. This formula requires no unusual pharmaceutical skill to compound and the cost is very much less than that of the proprietaries used for the same purpose. PHARMACOPEIA AM) PHYSIClAX. 314 The official sugar of milk and the unofficial urea cause diuresis, probably by acting on the renal epithelium. SCOPARIUS. Scoparius. — IT. S. — This is sometimes incor- rectly classed with digitalis because it slows the heart, but it weakens the beat while digitalis strengthens it. The alkaloid, spartein, is respon- sible for the cardiac and vasoconstrictor effect of scoparius, but the diuretic effect is due to sc-oparin, a glucosid. Average Dose (of scoparius) : 1 gm. (15 grains) The infusion or decoction is recommended for producing diuresis, except in dropsy. 3 Spartein* iE Sulphas. — IT. S. — While this is ob- tained from scoparius it is not a diuretic. Average Dose: 0.01 gm. (1/5 grain), but this dose is sometimes considerably exceeded. IRRITANTS. Irritants which are excreted by the kidneys pro- duce diuresis but. of course, they must not be used in greater amounts than are necessary to produce a mild stimulation. They are contraindicated in nephritis. The use of calomel in connection with squill and digitalis has been mentioned. It is most useful in cardiac dropsy and its use is to be stopped when 3. Scoparius Potassium bitartrate, each 3ss 15 1 This quantity of material is to be added to 1 liter (1 quart) of water, in a suitable vessel, boil for ten minutes. Allow to cool and strain. A wineglassful of the resulting decoction may he given every hour. DIURETICS AND DIAPHORETICS. 315 the diuresis becomes free. It may be given in doses of 0.2 gm. (3 grains) three times daily, or in the form of Njemeyer’s pills. VOLATILE OILS. The irritants include a number of volatile oils which are much more frequently used for their an- tiseptic action on the urinary tract than for any slight increase in renal action which they may cause. They include such volatile oils as oil of turpentine and oil of juniper, which are more often used as diuretics than copaiba, cubeb and matico, which are employed mainly as antiseptics. HEXAMETHYLEXAMIX. The* volatile oils have been largely superseded as urinary antiseptics by the now official hexamethyl- enamin. 4 Hexamethylamixa. — IT. S— ( Hexamethylen tetramin). This is a condensation product pro- duced by the union of formaldehyd and ammonia. While free from the irritating effect of formalde- hyd it yet retains its antiseptic properties, the formaldehyd being gradually set free by dilute acids. Being an ammonium derivative, a solvent effect on uric acid has been claimed for it, just as for lithium salts. It is readily soluble in water and is best given in solution. Average Dose: 0.25 gm. (4 grains). This substance has been introduced with some slight modification under various names; usually 4. The official name is very cumbersome, but no satis- factory substitute has thus far been suggested. Hexamethyl- enamin was first brought before the profession by Sobering under the trade name of urotropin CScbering & Glatz), and it is still sold by them under this name. It is also on the market under various other trade names, such as amniform, cystogen and others. 316 PHARMACOPEIA AND PHYSICIAN. the modification is only sufficient to enable the manufacturers to say that their product is not identical with the official. For instance, helmitol is anhydromethylen citric acid with hexamethylen- amin. "[Triform embraces two other drugs of minor importance. The official preparation may be con- sidered at least equal to them, since it is not mod- ified by any useless or inferior products, and its purity is easily insured by chemical tests. UVA URSI. Another drug of this class which has been the subject of much dispute is uva ursi. Its principal usefulness is probably in catarrhal conditions of the urinary tract. It contains a glucosid, arbutin, which is decomposed, but partly perhaps in the kidney, but more abundantly in contact with catar- rhal mucous membrane, hydroehinon, an antisep- tic, being formed. Uva Ursi. — U. S. — The dried leaves of Arcto- stapliylos Uva Ursi, of which the only official preparation is : Fluidextractum Uvje Ursi.- — U. S. Average Dose: 2 c.c. (30 minims). Infusion of uva ursi is made according to the general formula for infusions by pouring 1 liter (1 quart) of boiling water on 50 gms. (1 oz. 5 drs.) of bruised uva ursi. The fluid extract or the infusion may be given alone three or four times daily. Chimaphila. — U. S. — The dried leaves of Chimaphila umbellata , commonly called pipsisse- wa. It was introduced in America by Dr. John S. Mitchell in 1803, and later into England. Its medicinal action closely resembles that of DIURETICS AND DIAPHORETICS. 317 uva ursi, to which, however, chimaphila is in- ferior. Fluidextractum Chimaphila. — U. S. There remains to be considered an important class of substances which are used as diuretics, but they are so well known that only a very brief notice is needed here. The acetates or citrates of sodium and potassium increase the alkalinity of the blood and lessen the acidity of the urine or render it alkaline; they also increase diuresis. Potassium bitartrate and nitrate are also widely used as diuretics, mainly as additions to mixtures. For this purpose they are largely diluted with water, the latter alone being the most commonly used of all diuretics. Cantharides is very rarely used for its effect on the kidneys, as it is extremely irritant. DIAPHORETICS. The methods used for producing diaphoresis are analogous to those employed for diuresis, con- sisting in those which influence the circulation and those acting on the sweat glands; but in addition, certain agents, notably solution of ammonium ace- tate, act on the sweating center. The circulation in the skin is readily influenced by the application of heat in numerous ways nnd by, what amounts to the same thing, the prevention of its loss by an impervious cover, such as oiled silk, or by agents which cause dilation of the ves- sels of the skin, such as hot alcoholic drinks and spirit of nitrous ether. Everyone is familiar with the sweating of nausea, and while any nauseant will cause diaphoresis, the only one which is gen- erally employed for this purpose is the powder of 318 PHARMACOPEIA AND PHYSICIAN. ipecac and opium, the well-known Dover’s powder. The only official substance used for the purpose which directly stimulates the secretion of sweat is pilocarpus and its alkaloid, pilocarpin. They do not act on the secretory cells as eaffein does or on the kidney, but by stimulation of the secretory nerves. Diaphoretics are employed to arrest “colds” in the early stages, to aid in getting rid of fluid ac- cumulation, as in dropsy, and to a lesser extent for getting rid of secretions. Diaphoresis often serves to relieve the kidneys or to supplement their ac- tion. Vegetable infusions which cause diuresis will usually cause diaphoresis at the same time if the patient is kept warm and measures are taken to increase the blood supply of the surface (rubbing, mustard, etc.). For the arrest of “colds” nearly anything caus- ing sweating seems to be effective, but the powder of ipecac and opium enjoys a particular reputa- tion. Pulvis Morphine Compositus. — U. S. — Com- pound powder of morphin, also known as Tully’s powder, containing 1.5 per cent, of morphin and 32 per cent, of camphor, has also been recommended, and is sometimes used, as a diaphoretic, in place of the older and more popular Dover’s powder. Average Dose 0.5 gm. (7 grains). Potassium citrate, referred to as a diuretic, is much used for its diaphoretic effect, particularly in the form of : Liquor Potassii Citratis. — U. S. — This is an aqueous solution of potassium citrate, containing about 8 per cent, of anhydrous potassium citrate. Average Dose: 15 c.c. (4 fluidrachms). DIURETICS AX D DIAPHORETICS. 310 Spikitus AEtheris Xitrosi. — U. S. — Sweet spirits of niter. This is a very generally popular diaphoretic which is also used as a diuretic in fevers. Average Dose: 2 c.c. (30 minims). ' Liquor Ammonii Acetatis. — U. S. — The old- time spirit of Mindererus. Average Dose: 15 c.c. (4 fluidrachms). The only official drugs which have diaphoresis as their predominant therapeutic action are pilo- carpus and its alkaloid, pilocarpin. They are both too well known to require very extended notice in this place. Pilocarpus. — U. S. — Pilocarpus or jaborandi leaves contain, by assay, not less than 0.5 per cent, of alkaloids. Average Dose: 2 gm. (30 grains), given occa- sionally in the form of a 5 per cent, infusion, made according to the official general formula for that class of preparations. Fluidextractuvi Pii.ocarpi. — U. S. — This is made with diluted alcohol and contains 0.4 per- cent of the alkaloids from pilocarpus. Average Dose: 2 c.c. (30 minims). Pilocarpiyle Hydrochloridum. — TJ. S.. and Pilocarpenye Nitras. — U. S., are therapeu- tically identical. They are both very soluble in water. Average Dose (either) : 0.01 gm. (1/6 grain). CHAPTER XIV. CATHARTICS. Cathartics are among the most ancient of ail medicinal agents, rhubarb having been in use among the Chinese for more than forty-five cen- turies; senna and aloes were also used in ancient times. Liebig supposed that saline cathartics in concen- trated solution withdrew water from the blood by osmosis, thus maintaining the feces in a liquid or semi-liquid state. This idea gave place to Schmie- deb erg’s theory, which attributes purgation to the fact that the purgative salts, being slowly absorbed in the small intestine, come into the large intestine, where they prevent absorption of the intestinal contents, thus keeping the feces soft. Heidenhain concluded that osmotic pressure and physiologic activity of epithelium are concerned in absorption from the intestine, and that the retar- dation of absorption by salts is due to a lessen- ing of physiologic activity. Wallace and Cushny studied the action of ca- thartics on absorption from the intestine, and found that those compounds which give precipi- tates with calcium salts retard absorption more than others, and that dilute solutions of saline cathartics retard absorption of fluid from the stom- ach and small intestine, thus rendering the intes- tinal contents more fluid and more easily moved through the alimentary canal by peristalsis. When Jaques Loeb studied the effects of cer- tain salts which cause rhythmic contraction of CATHARTICS. 321 muscle, he noticed that those which produce mus- cular twitching and an increase in the excitability of nerves are the same as those which produce catharsis when they are introduced into the intes- tine. J. B. MacCallum has found that all the saline purgatives are very much more active when injected into the blood, causing peristalsis more promptly and in very much smaller doses than when given by the mouth. This is also true of their subcutaneous injection or of merely dropping the solution on the peritoneal surface of the intes- tine. He further found that this action is inhibited by a small amount of calcium chlorid or mag- nesium chlorid solution, when it is injected, or when dropped on the peritoneal surface of the in- testine. This inhibition is entirely analogous to that which occurs with calcium chlorid after stimulation of skeletal muscle by sodium citrate and other salts. MacCallum also found that the saline purga- tives cause a greatly increased secretion into the lumen of the intestine; this occurs even when ex- cised loops of intestine are suspended in saline so- lution, and he considers this intestinal secretion as much the more important factor in maintaining the feces in a semi-fluid state. So far from ad- mitting that the salines cause purgation by being excreted into the intestine after intravenous injec- tion, he claims that they must be absorbed from the intestine into the blood in small amounts, at least, before they can cause increased peristalsis and the stimulation of the intestinal glands to increased secretion, pointing, in support of this theory, to the much more rapid action when such small amounts are injected into the blood stream, than PHARMACOPEIA AND PHYSICIAN. :i22 when they are injected into the stomach or intes- tine. The stimulation of secretion and peristalsis in excised loops shows that it may be independent of the central nervous system, and the ring-like contractions seen after the application of barium c-hlorid points rather to its action on the muscular fibers than on the nervous mechanism of Auer- bach’s or Meissner’s plexus, but the precise seat of the action has not been determined. As an ex- ample of the minuteness of the dose required when this drug is applied to the peritoneal surface of the intestine, it is stated that three-fourths of a milligram (1/80 grain) of barium c-hlorid caused peristalsis in the rabbit. Vegetable cathartics, such as cascara sagrada and rhubarb, were also found to be much more ef- fective when used intravenously or subcutaneously than when given by the stomach. Their action is also inhibited by calcium chloric!, but to a less de- gree than in the case of salines. While these experiments are interesting in ex- plaining the mechanism of cathartics, it is not to be understood that the cathartics can be used in- travenously or even hypodermically, except in rare cases. Barium chloric! is ver} r poisonous, and even a small amount of magnesium sulphate injected into the blood would prove fatal. Meltzer and Auer have recently stated that magnesium salts immediately inhibit intestinal peristalsis when they are injected into the vein of an animal. MacCal- lum’s work, on the other hand, corroborates that of Claude Bernard, who found in 1857 that mag- nesium sulphate caused peristalsis when injected subcutaneously. Among the many theories advanced to explain CATHARTICS. 323 catharsis is that of Groesbeck Walsh, who remarks that the actions of cathartics in general agree with bacterial action in the liquefaction of feces, in causing increased peristalsis and increased gas formation. Hence, he concludes that the cathar- tics act mainly by promoting bacterial activity. Even the action of calomel is thus explained, as it inhibits the growth of other bacteria, thereby pro- moting the rapid increase of the colon bacillus with the results just mentioned. The use of purgatives is so general that it is usually considered a safe and harmless course, even when it does no good. This is true in the vast majority of cases, but Dr. M. L. Harris has recently called attention to the abuse of cathartics in conditions where they are potent for much harm. Among these he mentions : Closure of the intes- tine, as by strangulated hernia; complete local in- testinal paralysis ; localized spasmodic constriction, which tends toward spontaneous cure, but demands opium rather than cathartics ; appendicitis and peritonitis, in which it is agreed that irritant ca- thartics, at least, are contraindicated, whatever the individual opinion may be in regard to the use of the salines. Among the possibilities for the direst harm it may be pointed out that when a portion of the in- testinal tract is paralyzed, which may occur in ptomain poisoning, active cathartics might pro- duce intussusception by driving the healthy con- tracted bowel into the paralyzed relaxed portion. CLASSIFICATION - OF CATHARTICS. There is a fairly sharp distinction to be drawn between the action of the irritant vegetable ca- PHARMACOPEIA AMD PHYSICIAN. AU thartics and the non-irritant salines. One class of the vegetable cathartics depends for the activity of its members on derivatives of anthracene, another class on resin anhydrids. The preparations of the crude vegetable cathartics are usually but slightly soluble in water and dilute acids, but readily soluble in alkalies; they are, therefore, not absorbed from the stomach to anjr great ex- tent, but, being soluble in the intestinal contents, they act by irritating the bowel, or by being in part absorbed. They are much slower than salines in their action, producing evacuation of the intestine only after from five to twenty-four hours with moderate doses. These facts are of much im- portance in choosing a purgative when there is in- flammation of the intestine or other abdominal or- gans, as well as in pregnancy, since the irritation of the more drastic cathartics, by extending to the gravid uterus, may induce premature expulsion of the fetus. TREATMENT OF CONSTIPATION. First in the treatment of constipation, for which purgatives are well-nigh universally em- ployed, stands diet. By this means alone a very large proportion of cases of chronic constipation might be cured. It should contain a certain amount of indigestible residue, contrary to popular belief, and if the patient, in addition to correcting the diet, takes a fair amount of exercise in the open air and goes regularly to stool, but little pur- gative medicine will be needed. The effect of stewed prunes and other fruits is too well known to require detailed mention ; ap- ples. figs and strawberries are equally useful. It CATHARTICS. 325 ■ should also be remembered that a glass of cold water, alone, taken on rising, will often act as a laxative. Such simple remedies should always be tried be- fore resorting to drugs in chronic constipation, since the habit of taking laxatives in easily formed, but not so easily abandoned. Hydragogue cathartics are sometimes used in dropsy and to afford relief for the kidney. The excessive development of bacterial poisons in the intestine and their absorption into the blood causes symptoms varying from mere lassitude to profound shock. Purgatives sweep the bacteria and their poisons from the canal. Diarrhea, due to the presence of irritating mat- ter, such as undigested and fermenting food, is often promptly relieved by a saline purge. Saline purgatives are also useful in reducing fever, but they are not suited to cases of the asthenic type, be- cause of the exhaustion which they produce. THE ANTHRACENE DERIVATIVES. The vegetable cathartics of the first group which we shall discuss depend for their action on substances derived from anthracene. The graphic formula of this substance will help to show the relationship existing between several of these de- rivatives. Anthracene (C 14 H 10 ) consists of three benzene rings united thus: CH CH CH / \ / \ / \ HC C C CH I I I I HC C C CH \ / \ / \/ CH CH CH Anthracene. CH CO COH / X / \ / \ OHC C C CCH 3 till OHC C C CH \ ✓ \ / \ / CH CO CH Tri-oxy-methyl-anthraquinone. If an atom of H in the anthracene group is re- 326 PHARMACOPEIA AND PHYSICIAN. placed by one of 0, the compound is called an- thraquinone or anthrachinone. Other atoms of H may then be replaced by OH and the compound is called oxyanthraquinone, a prefix to the oxy showing the number of such OH groups in the compound ; thus the name tri-oxy-methyl-anthra- quinone indicates that four H atoms of anthra- quinone have been replaced, three by OH groups and one by a methyl group CH,. This compound is known as emodin. Emodin is found in all the drugs which owe their activity to the anthracene derivatives, but its constitution may vary in the arrangement of the substituted OH groups in different plants. Natal aloes contains no emodin, hence it is not a purgative for man, but it is not found in com- merce at the present time. Other members of this group of cathartics con- tain other principles besides emodin, which are derived from the anthracene nucleus ; thus chryso- phanic acid, or di-oxy-methyl anthraquinone, is also found in rhubarb, senna, rumex and probably in frangula. The name indicates that there are but tv r o OH groups instead of three, as in the case of emodin. Many other substances, the chemistry of which is obscure, are found in the cathartic drugs. Preparations of the crude drugs contain colloidal matter which enhances the action of the pure principles, and they are therefore to be preferred to the latter ; a fact to be remembered when read- ing the circulars of those nostrum makers who lay stress on their extraordinary facilities for supply- ing pure principles. The drugs of the anthracene group are char- CATHARTICS. 327 acterized by a mildly irritant action whereby they purge without producing inflammation, hence they are to be preferred to the resin anhydrids in chronic constipation, or when a strong irritant action is contraindicated. Aloe. — U. S. — Aloes, including the Barbadoes, Curasao, and the Socotrine, is the inspissated juice obtained from various species of aloe. It was known to the early Egyptians and Romans. One or more of the various species of aloes is offi- cial in every pharmacopeia. Natal aloes is now in- teresting only from a scientific point of view. Average Dose (of aloes) : 0.25 gm. (4 grains). Aloe Purificata. — U. S. — This was made of- ficial in 1860, because of the impurities present in Socotrine aloes, due to the crude method of col- lection. The dose is the same as that of aloes. Aloinum. — U. S. — This is a neutral principle, varying in physical and chemical properties with the variety of aloes from which it is obtained. It does not fully represent the crude drug, medicin- ally. xAverage Dose: 0.05 c.c. (1 grain). Extractum Aloes. — U. S. — This is the aque- ous extract evaporated to dryness. Average Dose: 0.12 gm. (2 grains). PiLTTLiE Aloes. — U. S. — Each pill contains 0.13 gm. (2 grains) of purified aloes and an equal amount of soap. Average Dose : 2 pills. PiLLLiE Laxative Compositje. — Each pill contains: Aloin, 0.013 gm. (1/5 grain); strych- nin, 0.0005 gm. (17125 grain) ; extract of bella- donna, 0.008 gm. (1/8 grain) ; ipecac, 0.004 gm. (1/16 grain) ; and glycyrrhiza, 0.045 gm. (2/3 328 PHARMACOPEIA AND PHYSICIAN. grain). This is a substitute for the proprietary pills, which cinder a variety of names have at- tained a wide popularity. Average Dose (laxative) : 1 pill. The other official preparations into which aloes enters are : Pills of Aloes and Iron, Pills of Aloes and Mastic (the well-known Lady Webster’s Din- ner Pill), Pills of Aloes and Myrrh, Compound Pills of Rhubarb, Vegetable Cathartic Pills (no calomel). Compound Cathartic Pills, Tincture of Aloes, Tincture of Aloes and Myrrh, and Com- pound Tincture of Benzoin. The last-named prep- aration does not contain enough aloes to make it useful as a laxative. Pills of aloes are a convenient form of administration, the soap furnishing the alkali needed for developing the activity of aloes. The pill acts slowly and causes considerable pelvic congestion, hence it is useful in inducing delayed menstruation and increasing it if scanty. For the same reason it, more particularly than other mem- bers of the group, is contraindicated in fevers, pregnancy and in inflammatory conditions of the pelvic organs. Alone, it is not so useful in chronic constipation, but it is often added to other purga- tives. The compound cathartic pill is the most popular of these combinations. Bile appears to increase the activity of aloes, and the formula given below is suggestive as a suitable form of administration : R. Aloe | Fel bovis insp. Saponis aa gr. xx 1 1 3 M. Ft. pil. No. 15. Sig. : Three at a dose. These may be coated with salol, to prevent their disintegration in the stomach. The coating is CATHARTICS. 329 rapidly done by simply melting the salol in a shal- low tin vessel, into which the pills are then drop- ped, and the vessel twirled until the salol solidifies. This method of coating is also applicable to other so-called enteric pills, which are intended to dis- solve only in the intestine. The tincture of aloes is so bitter that it is rarely used internally, but it is sometimes applied to bed sores and other local affections. Aloin alone is not so effective as aloes, but it is ex- tremely popular in such combinations as the com- pound laxative pill, which acts mildly after about sixteen hours. Senna. — U. S. — The Alexandria (short) and the Tinnivelly, or Indian (long), senna are inclu- ded in the official title. One, or both, of these is official in every pharmacopeia. Average Dose: 4 gm. (60 grains). Dluidextkactum Senn2E. — U. S.— This is now directed to be made first by removing the resin with strong alcohol and subsequently extracting the drug with diluted alcohol. Average Dose: 2 c.c. (30 minims). Sykupus Sennas. — IT. S. — Syrup of Senna is now a very much more acceptable preparation than was that of the previous Pharmacopeia, and the physician should see that his patient gets the better article when it is prescribed. It represents 25 per cent, of the fluidextract — from which the principle that causes griping has been removed with alcohol — with oil of coriander to flavor. It supplies an excellent substitute for the nostrums now becoming obsolete, which depend on senna for their activities, such as castoria and the various “fig syrups,” so called. 330 PHARMACOPEIA AND PHYSICIAN. For children one or two teaspoonfuls given alone at bedtime act as a gentle laxative; twice as much may be given as a cathartic. For adults twice as much is given as to children. This preparation is not disagreeable to the taste, but since children are usually averse to anything called medicine, it may be given in a little cocoa. Average Dose (as laxative for children) : 4 c.c. (1 fluidrachm). PULVIS GLYCYERHIZiE COMPOSITUS. — U. S. — This powder, previously mentioned, contains 18 per cent, of senna. It is widely used as a laxative. Confectio Senn^e. — U. S. — This represents 10 per cent, of senna, with cassia fistula, tamarind, prune and fig. It is substantially the same as the well-known proprietary medicine “Tamar- Indien.” Average Dose: 4 gm. (60 grains). Infusum Senios Compositum. — U. S. — For- merly known as “black draught” (not black drop). This represents 6 per cent, of senna, and 12 per cent, each of manna and magnesium sulphate, flavored with oil of fennel. Average Dose: 100 to 200 c.c. (3 to 6 fluid ounces). The only other official preparation containing senna is : The compound syrup of sarsaparilla. Senna is one of the best of remedies for chronic constipation, as its use does not entail a still greater tendency to that condition. It has the dis- advantages of a disagreeable taste and of causing griping, if used alone : this tendency is overcome by combining it with aromatics. The confection is useful for children and in pregnancy. The milk of the nursing mother who takes senna may purge CATHARTICS. 331 the child. The resin which causes griping may be removed by extracting the leaves with alcohol without loss of the cathartic principle, the official fluidextract being made from senna which has been thus treated. The compound infusion or the confection may be used alone. The compound powder of glycyr- rhiza is an extremely popular laxative. Bheum. — U. S.— Ehubarb is obtained in Thibet and China from sources still undetermined. This valuable drug has probably been in use longer than any other substance now used wholly as a medi- cine. Average Dose: 1 gm. (15 grains). The official preparations of Ehubarb are so numerous that we shall merely enumerate them, most of them being too well known to require ex- tended notice. They are : The Extract, Fluid- eixtract, Compound Pills, Compound PowdeT, Syrup, Aromatic Syrup, Tincture and Aromatic Tincture. The average dose of either syrup is 8 c.c. (2 fluidrachms) ; of the tincture, 4 c.c. (1 fluid- rachm) ; of the aromatic tincture, 2 c.c. (30 min- ims) . Ehubarb is useful in constipation associated with indigestion and catarrh of the small intestine, but not in chronic constipation, as the tannin present tends to increase the trouble after a time. All of the preparations are useful, but the aromatic syrup and the compound powder are probably the most popular, being especially useful in the sum- mer diarrhea of children. The extract, the fluid- extract and rhubarb in powder are all useful lax- atives. The compound pills are said to be more 332 PHARMACOPEIA AND PHYSICIAN. useful in the expulsion of gas and in chronic con- stipation. They are commonly given alone. The following has been much used, but it is largely empirical : R. Extr. rhei | Ferri reducti, aa gr. lx 4 Arseni trioxidi. Strychnin® sulph., aa gr. i 0 1 06 Quinin® sulph gr. lx 4| To be made into 40 pills; one to be taken before each meal. Rhamnus Pursh tan w. — U. S. — Cascara Sa- grada, or “sacred bark/’ is directed to be gathered a year before being used. It was introduced into medical practice in 1877, but as a domestic rem- edy in habitual constipation it was in use some time before that date in the region to which it is indigenous — the Pacific slope. It is now official in a number of pharmacopeias. It is not given in substance. Fluidextractum Riiamxi Purshiaioe. — U. S. — This is prepared with 40 per cent, alcohol. Average Dose: 1 c.c. (15 minims). Fluidextractum Rhamxi Purshiasl® Aro- maticum. — U. S. — The crude drug contains a bit- ter acid principle which is neutralized in this preparation with magnesia, orange and glycyrrhiza being added to flavor and sweeten it. There is no special skill required in making this preparation, and any reputable pharmacist can make it equally as well as the manufacturers who put it on the market in the form of proprietary preparations. Average Dose: 1 c.c. (15 minims). Extractum Rhamni Purshiax^e. — U. S. Average Dose: 0.25 gm. (4 grains). CATHARTICS. 333 Cascara sagrada is probably the most useful lax- ative in the materia medica for chronic constipa- tion. Unlike most of these remedies, which de- mand increasing doses, it improves the digestion, and the dose may be gradually diminished. Owing to the very disagreeable taste of the fluid extract, the aromatic fluid extract, or the extract, in pills or capsules, is to be preferred. THE ANHYDRID GROUP. The active principles in drugs of this group are resinous in character; their chemistry is obscure, but most of them are known to be glucosids. They cause violent irritation and even death in excessive doses and are not commonly used alone unless a strong irritant action is desired. Since they produce very watery stools, they are sometimes used in dropsy, or to sweep away parasites — for instance, after a narcotic tenifuge, such as aspi- dium. Jalapa. — U. S. — Jalap, the dried tuberous root of Exogonium purga, gathered in the neighborhood of Jalapa, Mexico, whence its name. The drug was introduced into Europe about 1609 ; it is now official in all pharmacopeias. The drug should contain not less than 8 per cent, of total resin, but not more than 1.5 per cent, of resin soluble in ether. Average Dose (in powder) : 1 gm. (15 grains). Pulvis Jalaps Compositus. — U. S. — This is a mixture of 35 parts of jalap and 65 parts of potas- sium bitartrate. Average Dose: 2 gm. (30 grains). Resina Jalapje. — U. S. — That part of the al- coholic extract which is insoluble in hot water. PHARMACOPEIA AX D PHYSIC I AX. 334 Average Dose: 0.12 gm. (2 grains). Colocynthis. — U. S. — The peeled dried fruit of Citrullus Colocynthis, a species of cucumber. As “Eolokynthis,” this drug was described by Dioscorides and appears to have been well known even before bis time ; since then it has been in con- stant use. Average Dose: 0.05 gm. (50 mg. or 1 grain). Extractum Colocynthidis. — U. S. — Average Dose: 0.030 gm. (30 mg. or % grain). Extractum Colocyntiiidis Compositum. — U. S. — Compound Extract of Colocynth is a mixture of 16 parts of extract of colocynth, 50 parts of purified aloes, 6 parts of cardamom, 14 parts of resin of scammony and 14 parts of soap. Average Dose: 0.50 gm. (7% grains). PiLULiE Cathartics Composite. — U. S. — Compound Cathartic Pills. Each contains : Comp. ext. of coloevnth . . . . . . .gr. iss 108 Mild mercurous clilorid . . . gr. i 1 06 Resin of jalap . . gr. 1/3 1 02 Gamboge .. gr. 1/4 |015 Average Dose : 2 pills. Piluls Cathartics Vegetabiles. — TJ. S. — Vegetable cathartic pills. Each contains : Comp. ext. of colocynth gr. i 1 06 Ext. of hvoscyamus gr. ss ! 03 Resin of jalap gr. 1/3 |02 Ext. of leptandra Resin of podophyllum, aa. . . .gr. 1/4 1 015 Oil of peppermint m. 1/8 ] 008 Average dose: 2 pills. Scammonium. — U . S. — Scammony, a gum- resin obtained by incising the living roots of Con- volvulus Scammonia, has been known and properly esteemed as an active cathartic for over 20 cen- turies. CATHARTICS. 335 Average Dose: 0.250 gm. (4 grains). Resina Scammonii. — U. S. — Resin of Scam- mony is that portion of the gum-resin that is soluble in alcohol, but insoluble in water. Average Dose: 0.200 gm. (3 grains). Podophyllum. — IT. S. — Podophyllum, popular- ly known as mandrake root or May apple, is said to have been used by the American Indians, but the statement has been repeatedly questioned. Average Dose: 0.500 gm. (7% grains). Fluidextractum Podopilylli. — U. S. Average Dose: 0.5 c.c. (8 minims). Resina Podophylli. — IT. S. Average Dose (purgative) : 0.015 gm. (15 mg. or 14 grain) ; (laxative) : 0.005 gm. (5 mg. or 1/10 grain). Leptandra. — IT. S. — Is rarely used in sub- stance. Extractum Leptandra. — IT. S. Average Dose: 0.25 gm. (4 grains). Fluidextractum Leptandrye. — IT. S. Average Dose: 1 c.c. (15 minims). Euonymus. — IT. S. — Euonymus is the dried bark of the root of Euonymus atropurpureus. The Extract (dose 0.12 gm. or 2 grains), and the Fluidextract (dose 0.5 c.c. or 8 minims) are also official. Elaterinum. — IT. S. — Elaterin, a neutral prin- ciple obtained from elaterium, a substance depos- ited by the juice of the fruit of Ecballium Ela- terium. Average Dose: 0.005 gm. (5 mg. or 1/10 grain) The therapeutics of the anhydrid group may be treated together, as the action of the different mem- 33fi PHARMACOPEIA AMJ PHYSICIAN. bers is very similar and there are few indications for one, rather than another, in a particular case. They are all used to some extent in dropsy, but elaterium is the most effective of all in the removal of water. They cause depression, and when this is severe it demands a stimulation. They are rarely used alone; thus scammony, which, in overdoses, has caused death, is used in the compound cathartic pill; jalap is often com- bined with calomel or with potassium bitartrate, in the compound jalap powder, which is adminis- tered alone. An example of the combination of calomel with jalap is the calomel and jalap pow- der of the National Formulary, which consists of: Calomel %\ 32 1 Jalap 3ii 64 1 The dose is about 1 gm. (15 grains), or a smaller amount may be given and repeated at in- tervals of several hours. Eesin of jalap is nearly tasteless and is, there- fore, often given to children ; it may be mixed with a little sugar for the purpose. Compound cathartic pills are so well known that they scarcely require further notice. The soap present (in compound extract of coloeynth) slowly reduces the mercurous chlorid to the black oxid — increasing its effectiveness. Podophyllum has been called “vegetable calo- mel” and it was supposed to increase the secretion of bile, but this is not probable. It causes purga- tion after ten to twelve hours and is very useful in acute constipation. A suitable form of administration is suggested below, but the possible combinations are endless. CATHARTICS. 337 The Triplex Pills (N. P.) have the following formula : R. Purified aloes gr. ii |12 Mass of mercury gr. i 1 060 Eesin of podophyllum gr. 1/4 J 015 Dr. John W. Francis has used a pill containing about 1 grain, each, of purified aloes, scammony and mass of mercury, with 1/20 minim of croton oil, minim of oil of caraway and enough tinc- ture of aloes and myrrh to make one pill. Leptandra, euonymus and some other official vegetable drugs cause purgation, but do not re- quire special mention here. Cambogia. — U. S. — Camboge is a gum-resin ob- tained from Garcinia Hanburii. Average Dose: 0.12 gm. (2 grains). PURGATIVE OILS. There are but two of these which merit discus- sion here. Castor oil and croton oil owe their ac- tivities to two acids, ricinoleic in the castor oil, and crotonoleic in the croton oil. The acid does not exist uncombined in castor oil, but is liberated when it reaches the intestine, forming new com- pounds which are irritant and therefore purga- tive. Crotonoleic acid does exist free to a small extent in croton oil, which is, therefore, irritant even when applied to the skin. Other bland fixed oils are sometimes used as laxatives. Among those which are official are Olive Oil, Cotton Seed Oil, and Expressed Oil of Almond. Oleum Eicini. — U. S. — Castor Oil, expressed from the seed of Ricinus communis, is a pale, yel- 338 PHARMACOPEIA AND PHYSICIAN. lowish or almost colorless, transparent, viscid liquid, having a faint mild odor, but an offensive taste. It was known to the ancients, but fell into disuse ; it was again brought into notice in 1764 by a West Indian physician, who described it as a gentle purgative. Average Dose: 15 c.c. (4 fluidrachms). Castor oil is very useful in ordinary constipa- tion, and often in diarrhea, when it serves to re- move the irritating substance. Owing to the widespread repugnance to the taste of castor oil, many means have been devised for disguising it. If the mouth is merely rinsed with strong whisky, the oil may be swallowed without discomfort. For children it is given in the form of soda water with syrup of sarsaparilla, or with ginger ale, when it is often swallowed without the child’s knowledge. The following formula is useful for disguising the taste : R. Spts. menth. pip 3iiss 1 0 1 01. ricini q. s. ad Siii 100 [ Sig. : 15 c.c. (4 fluidrachms) to be taken without further dilution. Emulsions of castor oil have never been popular, as they but imperfectly disguise the taste. Soft capsules, containing 15 minims each, may be swallowed, and many persons find them unobjec- tionable. Three or four capsules are given at bed- time. Oleum Tiglii. — U. S. — Croton Oil. A pale, brownish-yellow, fixed oil, expressed from the seeds of Croton Tiglium; it has a slight fatty odor, and a mild, oily, afterward acrid and burning taste. (Great caution is necessary in tasting). CATHARTICS. 339 Average Dose: 0.05 c.c. (1 minim). Owing to its irritant character and the violence of its action, croton oil is not generally used as a purgative, but there are conditions in which it is very useful; it may be given in apoplexy, when the patient is unconscious, a drop being placed on the tongue either in the form of an emulsion or on sugar. It is useful when, from any cause, there is difficulty in administering a bulky ca- thartic, but it is contraindicated in inflammatory conditions of the intestines. Croton oil is also applied to the skin as an irri- tant. LAXATIVE SWEET SUBSTANCES. Some of the following substances may be treated under the subject of dietetics, since they are laxa- tive mainly because of the bulk of non-absorbable matter. The dose is large and the action mild — with the exception of Cassia Fistula, which is apt to cause griping. Manna. — U. S. — The concrete saccharine exu- dation of Fraxinus ornus. It consists mainly of a peculiar sugar, mannite. Average Dose: 16 gm. (240 grains). Prunum. — U. S. — Prune, the partly dried fruit. Tamarindus. — U. S. — The preserved pulp of the fruit. Average Dose: 15 gm. (i/o ounce). Ficus. — U. S. — The partially dried fruit. Cassia Fistula. — U. S. — The dried fruit. This and the three preceding articles enter into confection of senna. 340 PHARMACOPEIA AND PHYSICIAN. Manna is a mild laxative, but it is rarely used alone ; it enters into the compound infusion of senna. BILE. Since many of the symptoms resulting from in- digestion and constipation were formerly attrib- uted to a deficiency in the formation of bile, agents were sought which would increase its secre- tion. Many of the purgatives now in common use were supposed to possess this property, but the only agent which has been shown by experi- ment to increase the secretion notably is bile itself. The precise role played by bile beyond the splitting of fats, is still a moot point. In this connection it may be mentioned that the mineral acids, particularly the dilute nitro-hydro- chloric, have been much used for their supposed cholagogne action; this is too slight to give them practical value, but they are useful in many con- ditions for which a deficiency of bile is supposed to be the cause. Dr. Philip Shaffer recently gave a woman with biliary fistula about 20 gms. (5 drams) of the purified ox bile in three days, resulting in a notable increase of bile secretion. The patient’s general condition seemed to be but little affected by the absence of bile from the intestine, but fats were not so well borne as in a normal person. This but confirms the experience of other observers, and in this light cholagogues lose much of their importance. Fel Bovis. — D. S. — The fresh bile of the ox is only used in the form of : CATHARTICS. 341 Fel Bovis Perifacttevi. — U. S. — Its use has already been mentioned. Average Dose : 0.5 gm. PHENOLPHTHALEIjST. Phenolphthalein is not official as a medical sub- stance, but is mentioned in tlie Pharmacopeia, in the list of reagents and test solutions, as an indi- cator in a ni di mi try. It has attracted some attention of late as a laxa- tive. In combination with soap and salicylic acid, it is being widely advertised under the name of “Probilin.” 1 SALI3STE CATHARTICS. A salt may be defined as a substance resulting from the chemic union of an acid with a base. For the present purpose we shall exclude from this classification salts of alkaloids and of other popular conception of salts, or purgative salts, organic bases, and confine our definition to the - The purgative salts, in contrast to the antiquity of many of the vegetable cathartics, are of but comparatively modern use, ma'ny of the inorganic salts being introduced into Europe by the Moors, but not coming into general use until after the time of Paracelsus. 1. The proprietors of probilin quote Dr. W. Bauermeister of Brunswick, Germany, as authority for the assertion that salicylic acid and sodium oleate are the most powerful cholagogues. This is not in accord with the generally ac- cepted opinion of therapeutists. The same authority states that he had the two drugs put up in pills containing iy 2 grains of each, adding menthol and phenolphthalein as anal- eptics and to mildly stimulate intestinal activity. But we' are unable to understand why he should add “these pills, named probilin, are difficult to prepare.” At least, any com- petent American pharmacist can readily prepare them. Three or four of these pills taken before retiring are said to be effective. 342 PH ARM A COPE [A AND PHYSICIAN. Most of the purgative salts have a disagreeable, bitter taste, but when taken in an effervescing draught this bitterness is masked, and the efferves- cent salts have therefore come into great popular- ity. The widespread use of nostrums of this type, instead of the official effervescent salts prepared by the pharmacist, illustrates an unfortunate condi- tion which exists without a sufficient reason. There is too much distrust of the pharmacist by certain physicians, who complain that pharmacists are un- able to supply preparations equal to those of the nostrum maker. This may possibly be true in isolated cases, hut the proof to the contrary is fur- nished by the extreme simplicity of the prepara- tion of the effervescent salts which the average pharmacist can prepare quite as well as the large manufacturer. Nevertheless the nostrums of this class have an enormous sale. It is unfortunately true that the physician often lacks confidence in himself and prefers to use the ready-made mixtures rather than to exercise his own choice. This is degrading alike to medicine and to pharmacy. It is a part of our present purpose to illustrate the ease with which the physician may choose his own agents in the proportion which seems best adapted to each individual case, with the assurance that any honest pharmacist can compound his prescription in a form equal in efficiency and ele- gance to the nostrums. The preparation of the effervescent salts de- pends on the fact that tartaric and citric acids and sodium bicarbonate may he kept in contact with- out change when dry, but unite with effervescence when they are dissolved in water. CATHARTICS. 343 As an example of the ease with which efferves- cent salts are prepared, we give directions for mak- ing one, which, though extremely simple, is still the most complex of those which are official — The Effervescent Magnesium Sulphate. The same di- rections, with slight modifications, are used in pre- paring the other official granular effervescent salts and may be used when it is desired to include other salts or even caffein and similar substances. The magnesium sulphate is dried over a water bath, powdered and mixed with powdered citric and tartaric acids, then with the sodium carbonate ; the mixture is heated to about 95° C. in a dish placed in an oven until it becomes moist ; it is then rubbed through an ordinary tinned iron sieve (which forms it into granules). These are then dried at a temperature of 54° C. Does it seem credible that any pharmacist is un- able to make so simple a preparation as that ? Many of the nostrums that are offered to physi- cians as effervescent saline mixtures are not even granulated, and some of them, at least, depend en- tirely on the use of the cheaper tartaric acid and sodium bicarbonate to produce effervescence. Mix- tures of this kind can be prepared extemporane- ously quite as readily as the frequently prescribed liquid preparations. Constipation is by far the most common com- plaint of those who live in cities. While the rational treatment consists in attention to the diet and other hygienic measures, for the most part, it is so much easier to read one of the innumer- able advertisements which depict the terrible con- sequences of constipation, and the one certain means of escape therefrom, that the credulous are 344 PHARMACOPEIA AND PHYSICIAN. inclined to accept such statements as true, and, in a way, lionize themselves because of the dangers they have encountered and escaped. Any attempt merely to enumerate the financially successful nostrums of this type involves one in immediate difficulties, because of the enormous number of those advertised to the public, while those of this type advertised to physicians are scarcely less numerous. The principal purgative salts and their indica- tions are so well known that we shall confine our- selves mainly to enumerating some of them, with suggestions for the forms in which they are avail- able, and a few of the combinations which may be found useful. We shall have occasion to contrast the well-known actions of these drugs with the absurd claims made for some of the nostrums which they compose. Magnesii Sulphas. — IJ. S. — Epsom Salt (by which name it is most widely known) is so called because it was formerly obtained by evaporating the water of Epsom Springs. It is one of the chief constituents in many famous purgative waters, such, for instance, as the Hunyadi of Hungary. Average Dose: 15 gm. (4 drams). Magnesii Sulphas Efeebvescens. — U. S. — (Its preparation has been detailed.) Average Dose: 15 gm. (4 drams). Magnesii Cakbonas. — U. S. — A bulky, white, colorless and nearly tasteless powder, which is in- soluble in ordinary solvents. Average Dose: 3 gm. (45 grains). Magnesii Oxidum. — U. S. — This, commonly called magnesia, or calcined magnesia, closely re- sembles the carbonate in its several properties. CATHARTICS. 345 Average Dose: 2 gm. (30 grains). Magnesii Oxidum Poxderosum. — U. S. — This differs from the preceding only in being more dense, and therefore requiring a less bulky dose. It was formerly known as Husband’s, also as Henry’s magnesia. Average Dose: 2 gm. (30 grains). Liquor Magnesii Citratis. — H. S. — This, al- most always called “citrate of magnesia,” is one of the most agreeable of the purgative preparations, but it does not keep well, and should therefore be ordered freshly prepared. Average Dose (as purgative) : 360 c.c. (one bot- tle). Magnesium carbonate is frequently employed as an ant-acidq the oxids, light and heavy, are ant- acid and laxative. The oxids should be given with a large excess of water. They are much used for children. Potassii et Sodii Tartras. — H. S. — This is commonly called Rochelle salt because it was first manufactured in the city of Rochelle. It was dis- covered by a pharmacist named Seignette and is often called Seignette salt by the French. Average Dose: 8 gm. (120 grains). Pulvis Effervescens Compositus. — U. S. — Seidlitz powder is the form in which Rochelle salt is most often used. Sodii Phospkas. — H. S. — This has come into very general use of late years in the treatment of chronic constipation, and it is popularly believed to exert a special influence on the liver. It is soluble in about six parts of water. Average Dose: 2 gm. (30 grains). 340 PHARMACOPEIA A. XL) PHYSICIAN. Sodii Pi-iospiias Eppervescens. — U. S.— This is much more pleasant to take than the ordinary sodium phosphate, of which it contains 20 per cent. Average Dose: 8 gm. (120 grains). Sonir Phosphas Exsiccates. — U. S. Average Dose: 1 gm. (15 grains). A preparation so well known as sodium phos- phate requires little therapeutic notice., but we wish to offer some suggestions as to the forms in which it is available. The effervescent salt leaves little to be desired when one wishes to employ it as a laxative, but it is not well adapted for use with hot water. We give below several examples of its combina- tion. In one of these lithium citrate is used. Of course, these combinations may be endlessly varied, using the dried magnesium sulphate, for instance, instead of the dried sodium phosphate. Catfein is often used with effervescing salts, and this or other similar substances ma} r be incor- porated without materially changing the formulas. It. Lithii citratis . 3i 4|0 Sodii phosph 3viii 30 1 0 Sodii bicarb 3x 40 10 Acidi tartarici 3vi 25 1 0 The dose of this is about 4 gm. (60 grains). For use with hot water the following extem- poraneously-prepared mixture is preferable to the official effervescent salt: It- Potassii bitart 3x 40 1 0 Sodii bicarb 3v 20 0 Sodii phosph. exsic 3x 40] 0 The dose of this preparation is the same as that of the one preceding it. In ease a more alkaline CATHARTICS. 347 mixture is desired the amount of sodium bicarbon- ate may be slightly increased and the potassium bitartrate correspondingly decreased. Liquor Sodii Phosphatis Compositus. — U. S. — One c.c. represents 1 gram of sodium phos- phate. Average Dose: 8 c.c. (2 fluidrachms). To make this solution, the Pharmacopeia directs that 100 gm. of sodium phosphate and 4 gm. of sodium nitrate be triturated together in a mortar with 13 gm. of citric acid, until completely lique- fied, then sufficient water is to be added to make the product measure 100 c.c. Although this requires no more skill than the weighing of the salts, the Alta Chemical Company pretends that it thus secures “An Ideal Nerve Tonic, Laxative, Analgesic ! Stimulant of Gland- ular Function, adjuvant to all organic remedies indicated in the organism ! relieving Hepatic Con- gestion, supporting Sexual Power, regulating both excretion and secretion on a normal physio- logic basis !” The indications enumerated are far too absurd to be repeated in full, but as an example of this word waste we quote the following: “Especially reliable as a painless cure for the Morphin Habit !” Does this insolent company suppose that we are bereft of every vestige of intelligence when it in- sists on telling us such manifest falsehoods as we have quoted or that Rheumagon, consisting of sodium iodid and sodium phosphate, is “a specific in all cachectic diseases l” Surely. Baron Munchausen, in his wildest flights of fancy, never imagined anything more preposter- ously absurd. 348 PHARMACOPEIA AND PHYSICIAN. When we see how simple is the preparation of the various effervescent salts, and remember that the Pharmacopeia provides reasonably high stand- ards and readily applied tests for the purity of all official salts, with which all reputable manufactur- ers of chemicals comply, we see how absurd is the pretense of the nostrum makers that they have special processes and peculiar facilities for manu- facturing products of superior quality. Liti-iii Carbonas. — U. S. — It is more than sixty years since Lipowitz announced that this salt favored the solution of uric acid. Since then the lithium salts have been widely used, especially in combination with purgatives and diuretics, but there is no evidence that any benefits result from such combinations. The lithium salts are of comparatively little im- portance according to the accepted authorities in therapeutics of to-day. Average Dose: 0.5 gm. (8 grains). Lithii Citras. — IT. S. — Is used for the same purposes and in the same dose as the carbonate. Lithii Citras Effervesced. — IT. S. — Is a convenient form for administering the citrate. Average Dose: 8 gm. (120 grains). Lithium salicylate was made official in 1880 be- cause of its asserted superiority in the treatment of acute rheumatism; it possesses no advantages over the other salicylates, but the nostrum makers hav- ing seized on it while the first reports of its success- ful use were being circulated, they continue to make the most extravagant claims for it in their preparations. Cushny specifically denies that this salt has any especial solvent action on uric acid in acute rheumatism; this should be borne in mind CATHARTICS. 349 when free circular pharmacology is under consider- ation. Sal-lithin is typical of a host of nostrums which consist of lithium and purgative salts. It is made by the firm which exploits the thoroughly dis- credited bioplasm by such absurd misstatements and reprehensible methods. (See The Journal, vol. xlv, pp. 1587-1812.) The number of uric acid solvents, each of which is the “most powerful known,” is truly surprising. It is still more surprising that mankind continues to suffer from rheumatism and gout, nearly as much as they did before these “discoveries” were made. Mr. J. LeRoy Webber, Ph.G., is credited by the Bristol-Myers Co. with originating sal hepatica, the really “most powerful” one. This truly won- derful discovery of Mr. J. LeRoy Webber, Ph. G., is also useful, so we are told, in the treatment of “Fullness of Blood,” likewise “Acidity of the Stomach,” though most of us prefer some acidity of the stomach and not a little blood to fill our arteries. If further literature of a similar nature is de- sired, we suggest the careful reading of the ITric Acid Monthly , particularly with regard to the munificent offer for reports “suitable for publica- tion.” It must be evident to the least observant that we are drifting far from the safe course in thera- peutics when men, who have not sufficient knowl- edge to avoid absurdities so glaring that they be- come apparent on the first appeal to reason, ex- ploit our profession and use us to dupe the public. Are we to continue in this degrading position or 350 PHARMACOPEIA AND PHYSICIAN. are we to assert our independence and demand common sense, at least, from those who seek to serve ns ? The arrogance of the nostrum vendors under the cloak of servility is become insupport- able, and physicians should no longer tolerate such abuses. While we have divided the cathartics (under which term we include laxatives) into two gen- eral classes, vegetable and saline, this has been done merely for convenience of grouping, and we shall now take up the more important laxatives and cathartics which have not been discussed. Hydrargyrum Cum Creta,. — U. S. — Gray Powder. — This contains 38 per cent, of mercury (metallic) mechanically mixed with clarified honey and prepared chalk. Average Dose: 0.25 gm. (4 grains). Massa Hydrargyri. — IT. S. — The well-known “blue mass” contains 33 per cent, of mercury (metallic) combined with glyeyrrhiza, althea, gly- cerin, and honey of rose. Average Dose: 0.25 gm. (4 grains). Hydrargyri Chloridum Mite.- — H. S. — Calo- mel is required by the Pharmacopeia to contain at least 99.5 per cent, of pure mercurous ehlorid. There is, perhaps, no drug which is better known than calomel, and we can afford to give it space in inverse proportion to its importance. Average Dose (as a laxative) : 0.12 gm. (2 grains) . Despite the widespread use of the mercurials, their mode of action remains a problem. Some authorities assert that calomel must be converted into the oxid. others that small amounts of the bi- chlorid are formed, and that this is the active CATHARTICS. 351 agent. The effect on the organism is not less a matter of dispute ; pharmacologists usually deny that it causes an increase of bile-flow, as experi- ments, made by careful observers, on both man and animals with biliary fistula, have failed to demonstrate any increase. Calomel acts as an an- tiseptic and the bile is thus protected from decom- position, while the increased peristalsis affords less time for its absorption. Some of the older clin- icians, however, still hold to the theory that it really does increase the amount of bile secreted by the liver. However calomel may act, it is the best remedy we possess for that form of indigestion and constipation which is frequently called “bilious- ness.” Mercury and chalk, commonly called gray pow- der, does not occasion so much nausea as the other mercurials in common use, and is usually preferred for children who suffer with indigestion and con- stipation with considerable intestinal putrefaction. The mercurials are contraindicated in chronic conditions, such as tuberculosis, and in the latter months of pregnancy. The use of calomel as a diuretic has been mentioned, and, while Wood pro- nounces it useful in chronic parenchymatous nephritis, others maintain that it is injurious, and Sollmann has recently suggested that great conservatism should be exercised in its employ- ment. At any rate it should not be used merely for its purgative effect when nephritis exists, or only with great caution. Sulphur Precipitatum. — IT. S. — Sulphur Sublimatum. — IT. S. — and Sulphur Lotum. — TJ. S. — These are the three forms in which Sulphur is now official. Either the sublimed or the washed 352 PHARMACOPEIA AND PHYSICIAN. may be used as a laxative. The sulphur is slowly converted in the intestine into the sulphid, only to a small extent, which acts as an irritant, while the greater part of the sulphur remains insoluble and acts mechanically— merely by its bulk. Washed sulphur is an ingredient of compound powder of glycyrrhiza. Average Dose (of any of the three forms of sul- phur) : 4 gm. (60 grains). CHAPTEE XV. PARASITICIDES AND ANTIGONOR- EHEICS. It will be convenient to consider under this head, agents used for parasites other than bacteria, which infest the skin and intestines, together with a brief reference to the antigonorrheics. Cleanliness prevents nearly all hurtful skin parasitism, and the only one which we shall con- sider here is that of the pediculi, since other forms are commonly treated more advantageously by the specialist. The louse which infests the head requires no medication, since it is easily removed with a fine comb and thorough washing with tar soap. The ointment of red mercuric osid or red precipitate has been used as a popular domestic remedy, and the tincture of larkspur or of stavesacre, to be men- tioned again later, may be useful in many cases. The louse which infests the genital regions, Pediculus pubis, is smaller and more difficult to remove mechanically. A dilute solution of mercuric chlorid (corrosive sublimate) is sometimes used and is very effective for this troublesome parasite. It should not be stronger than one to five hundred (2 grains to 2 fluidounces or 0.1 gm. to 50 c.c.), and this should be used cautiously. A less cleanly but very effi- cient remedy is mercurial ointment. A 20 per cent, tincture of staphisagria, or larkspur, diluted with water, bay rum, dilute alco- 354 PHARMACOPEIA AND PHYSICIAN. hoi or soap liniment is much used in some parts of the country. Among the names of staphisagria which indicate its common use are semen staphidis pedicularis and lausekorner. In lieu of the unofficial tincture the now offi- cial : Fluidextractum Staphisagria. — U. S. — Di- luted with from 8 to 10 parts of soap liniment, or of bay rum, will be found equally serviceable. It may not be amiss to call attention to the fact that carbolic ointment not only kills the trouble- some chigger, but also relieves the smarting which that parasite occasions, or which is more fre- quently caused by scratching the place where the parasite is embedded. ANTHELMINTICS. The term anthelmintic, meaning literally against a worm, embraces vermifuges and tenia- fuges, which expel the round and tape worms, re- spectively, and vermicides and tenicides which kill them; but, as a matter of fact, the parasites are rarely killed before their expulsion. Kiiehenmeister attempted to establish a rational basis for the use of anthelmintics, more than fifty years ago, but his work, which was widely quoted for a long time, has but little value at present. v. Schroeder studied the effects of a large num- ber of agents on ascarides and found that the lat- ter are remarkably resistant to poison placed in the media with the parasites, which are to a certain ex- tent able to resist absorption. These parasites are surrounded by a chitinous substance, and when that is not acted on by the agent the mouth is the PARASITICIDES, ANTI GONORRHE ICS. 355 principal means of ingress to tlieir bodies. San- tonin, even in concentrated solution, was found to be harmless to the parasite, which, however, found it objectionable and sought to escape from the so- lution containing it, the movements being partic- ularly active; from this it would appear that san- tonin drives the round worm out of its normal habitat into the large intestine, from which it must be swept by purgation. The statement that the presence of castor oil greatly increased the toxicity of santonin for this parasite arose from a mistake, and santonin is now usually given with calomel. Since it is not in- tended to be dissolved in the stomach, a compressed tablet or lozenge of calomel and santonin is to be preferred. For the same reason, when santonin is given to a child, with a little sugar, the two sub- stances should be lightly rubbed together without being powdered. Sodium santoninate which is sol- uble, should not be used, therefore, and it has, very properly, been dismissed from the later editions of our Pharmacopeia. The following are among the now official sub- stances that are useful as vermifuges. Santonica. — IT. S. — Santonica or Levant worm seed, as it is frequently called, is officially de- scribed as the dried unexpanded flower heads of Artemisia pauciftora. It is now seldom employed as such, being generally displaced by: Santoninum.— IT. S. — Santonin, the inner an- hydride or lactone of santonic acid, obtained from santonica, was discovered in 1830, by two German apothecaries, quite independently of each other, Kaliler in Diisseldorf, and Alms in Mecklenburg. Average Dose: 0.06 gm. (1 grain). 356 PHARMACOPEIA AND PHYSICIAN. Spigelia.- — U. S. — Spigelia or pink root is the dried rhizome and roots of Spigelia marilandica. Average Dose: 4 gm. (60 grains). Fluidextractum Spigelle. — U. S. — This is made with diluted alcohol and is the preparation now generally used when this drug is to be admin- istered. Average Dose: 4 c.c. (1 fluidrachm). Oleum Chenopodii. — U. S. — Oil of Chenopo- dium is a volatile oil distilled from Clieno podium anthelminticum, more popularly known as Amer- ican wormseed. Average Dose: 0.2 c.c. (3 minims). Quassia. — U. S. — The wood of Picrasma ex- celsa, Jamaica quassia, or of Quassia amara, Sur- inam quassia, is more frequently used in the form of a decoction or an infusion, made in accordance with the general formulas for these several prep- arations. Average Dose: 0.5 gm. (7% grains). Extractum Quassia. — IT. S. — This is an aqueous extract and represents ten times the weight of the crude drug. Average Dose: 0.06 gm. (1 grain). Fluidextractum Quassia. — U. S. — This is directed to be made with a mixture of three parts of alcohol and six parts of water. Average Dose: 0.05 c.c. (8 minims). Tixctura Quassia. — IT. S. — This is a 20 per cent, tincture and is made with 35 per cent, alco- hol. Average Dose: 2 c.c. (30 minims). The Ascaris lumbricoides, or round worm, is a very common parasite in the small intestine of children particularly. The most useful remedy PARASITICIDES, ANTI GONORRHE ICS. 357 for this parasite is santonin; this has been given in a variety of methods. Some authorities recom- mend from one-half to one grain (0.02 to 0.05 gm.) morning and evening during three days for a child and on the fourth day a purgative. This suggestion was evidently based on the supposition that the parasites were killed or injured and were then to he swept out, but since we know that this is not true, the method in vogue at the present time is to combine santonin with a slowly acting purgative, such as calomel in small doses. The purgative should follow the santonin in a few hours at the latest. It should be remembered at all times that santonin is not an absolutely safe remedy and that it is far better to try a small dose and to repeat it in a few days if not effective than to give the maximum dose in the beginning. A lozenge containing half a grain (0.03 gm,) of santonin given morning and evening, to a child, for three days will usually be found effective. Twice, this dose is used for an adult. If it is desired to give santonin in powders, it may be prescribed somewhat as follows : Santonini (ervst.) . , . .grs. iii 012 Saeehari . .grs. xxx 2| M. Ft. in chart. No. vi div. Sig. : One powder night and morning, the last dose to be followed by a purgative. The purgative may consist of calomel or syrup of senna, or, according to the more modern teach- ing, 1/6 grain (0.01 gm.) of calomel may be di- rected to be incorporated in each paper. The mix- ture should be dispensed in granular form and not finely powdered. Santonin taken in this way has very little taste. 358 PHARMACOPEIA AND PHYSICIAN. While santonin is perhaps the most effective remedy we have for ascarides, the fluidextract of spigelia has been recommended and is said to act somewhat like santonin. It is recommended that a laxative be given before the spigelia and a pur- gative some hours later, or the combination of pink root and senna, that was at one time quite com- mon, may be preferred. Spigelia, however, has also given rise to toxic symptoms in children. Oil of chenopodium, or oil of American worm- seed, has long enjoyed a certain reputation, par- ticularly as a household remed} r , for round worms. It has a very disagreeable odor and taste. It may be given combined with eastor oil, or from one to three drops may be mixed with sugar for a child. The thread worm or pin worm, Oxyuris vermic- ularis, infests the rectum and colon, and is often spoken of as the seat worm. The common anthelmintics, such as santonin, together with purgatives, are usually effective in removing them, but they sometimes prove very troublesome and difficult to dislodge. Injections of large amounts of watery infusions are often useful. Infusion of quassia enjoys an es- pecial reputation, it lessens the mucus secretion and probably increases the movements of the para- sites, which facilitates their removal when the bowel is emptied. As suggested in connection with the official preparations of quassia, an aqueous infusion, the extract or even a correspondingly diluted fluidex- tract may be used, with some promise of satisfac- tory results, in cases in which the infusion can not be readily obtained. PARASITICIDES, ANTIGONORRHEICS. 359 Phenol has also been recommended, but the danger of absorption entirely precludes its com- mon use. Osier recommends the cold injection of a strong solution of common salt for children, repeated for ten days at least. The hips are elevated to favor the retention of the injection as long as possible. TENIAE ITGES. Eemedies used for tape worm are commonly spoken of as teniafuges, even though the parasite may belong to a different genus, but as a matter of fact, the Tania saginata, which is derived from beef, is very much more commonly found in the human intestine, while Tania solium from swine is met with much less frequently in man. Bomriocephalus latus is mentioned in all test- books, but as it is extremely rare in this country, and practically never originates here, it may be disregarded in this place. Male fern, or the much more widely used oleo- resin. which fully represents the rhizome, is said to be very much less efficacious against the Tania than against the Bothriocephalus , while pelletierin, obtained from the bark of pomegranate root, is es- pecially efficacious against the Taenia. If this be true we have but another example of our tendency to take everything originating in Germany as be- ing universally correct, without exercising our own judgment, for male fern has certainly enjoyed a greater popularity than the circumstances appear to justify. On the other hand, its wide use in northern Germany is more rational, since the Bothriocephalus is very commonly found there in man. Yon Schroeder found that one part of pelletierin 300 PHARMACOPEIA AND PHYSICIAN. in ten thousand parts of a solution containing 1 per cent, each of sodium chlorid and sodium car- bonate, was very rapidly fatal to Toenia serrata and to Toenia inermis, while much stronger solutions were practically harmless to round worms. Estimating the content of the human intestine at 200 c.c. after purgation, if only 0.2 gm. (3 grains) of pelletierin escape absorption from the stomach and pass into the intestine, it would be present in the proportion of one part in one thou- sand of intestinal content, or ten times the concen- tration found necessary by von Schroeder. Pelletierin is but mildly toxic to man, hence it appears to be an almost ideal teniafuge or teni- cide. Kamala, which was formerly official, and is still used, acts as an intestinal irritant, causing purging and therefore requiring no subsequent purgative. It is said to be effective against tenia and is usually administered in substance, being given in doses of from 4 to 8 gm. (one to two drachms). Kosotoxin, obtained from kousso, resembles male fern in its pharmacologic action, but is said to be efficacious against Toenia as well as against Botli- riocephalus. Aspidium, or male fern, has repeatedly given rise to toxic symptoms and death has occasionally followed its use. It is apparently inferior to pome- granate in the treatment of tenia, and there seems to be little reason for giving it the preference. Filicic acid was formerly regarded as the active principle; however, it seems that there are a num- ber of principles which share the action. Pumpkin seed enjoys some reputation as a teniafuge, but it is not often prescribed alone. PARASITICIDES, ANTIGOKORRHEICS. 361 It lias, at least, the advantage of not being toxic to the patient. SOME OFFICIAL SUBSTANCES USED AS TENIAFUGES. Aspidium. — IT. S. — Aspidium, or male fern, the dried rhizome of Dryopteris Felix-mas or of Dry- opteris marginalis, Mas known to Dioscorides, and advocated by him as being an efficient remedy for tape worm, but fell into disuse and was subse- quently nearly forgotten until revived as a secret remedy, for the same parasite, about the middle of the eighteenth century. Average Dose: 4 gm. (60 grains). Oleoresina Asptdii. — U. S. — Oleoresin of As- pidium is now directed to be made with acetone. This preparation was first suggested by Peschier of Geneva, about 1825, and has gradually displaced the other preparations of male fern. Average Dose: 2 gm. (30 grains). Granatum.- — U. S. — Pomegranate, the bark of the stem and root of Punica Granatum, was also known to the ancients as a remedy for tape worm. It appears to have been completely forgotten and was introduced into Europe from India during the first decade of the nineteenth century. Average Dose: 2 gm. (30 grains). Fluidextractum Granati. — U. S. — Fluidex- tract of Pomegranate is made with a menstruum of diluted alcohol containing 10 per cent, of gly- cerin. This is a new addition to the Pharmacopeia and has, as yet, not been widely used. Average Dose: 2 c.c. (30 minims). Pelletier in je T annas. — IT. S. — Pelletierin Tannate is officially described as a mixture, in varying proportions, of the tannates of four alka- 362 PHARMACOPEIA AND PHYSICIAN. loids (punicin, iso-punicin, methyl-punicin and pseudo-punicin) obtained from Punica Granatum. Average Dose: 0.25 gm. (4 grains). Cusso. — U. S. — Kousso, also known as kosso, koso and Brayera, consists of the dried panicles of the pistillate flowers of Hagenia abyssinica. It was discovered by Bruce, about 1768, but was not generally known as an anthelmintic until after Braver, in 1822, published his observations on the use of the drug in Constantinople. Kousso is usu- ally administered in the form of an unstrained in- fusion, the object being to secure mechanical irri- tation by the hairs which are found on the flowers, but they probably play only a minor part in the ac- tion of the drug. Average Dose: 16 gm. (240 grains). Pepo. — U. S. — Pepo, or pumpkin seed, the ripe seed of Cucurbita Pepo , is usually administered in the form of the ground seed, deprived of the hull, or as an emulsion, prepared by treating the ground seed with hot water. Average Dose: 30 gm. (1 ounce). The tannate of pelletierin, being slightly sol- uble, is preferred as a teniafuge, but it is some- what expensive, and the decoction of the root bark is therefore frequently directed. It has been sug- gested that the alkaloid, being volatile, is driven off in the process of boiling, but the loss in this way has proved to be unimportant. The fresh bark is much more efficacious than that which has been kept for some time. It is stated that the deteriora- tion is due to chemical change that takes place in the alkaloid. As we have no means of knowing the quality of PARASITICIDES, ANTIGONORRHEICS. 363 the bark which will be used in making the decoc- tion, it is better to use the pelletierin tannate or to direct the preparation of the extract 1 made ac- cording to a formula devised by von Schroeder to enable one to get a fairly uniform product regard- less of the cpiality of the bark used. About one gram or less of the extract, together with one or two grams of tannin, constitute the ordinary dose for tape worm. Pomegranate root bark contains a large amount of tannin, too much, in fact, considering the amount of bark required to yield the requisite amount of pelletierin, hence none has to be added to the decoction. So abundant is the tannin that it may cause vomiting and defeat the purpose for which the dose is given, hence the extract men- tioned has a decided advantage over the decoction. The following is the method of using pelletierin tannate, the extract described above, or the decoc- tion. Beginning in the evening the patient takes a light meal, which should be exclusively of carbo- hydrates, and then a laxative; on the following morning, while fasting, he takes 0.4 to 0.5 gm. (6 to 8 grains) of pelletierin tannate, or a correspond- ing amount of the extract or decoction, followed in half an hour or two hours by a brisk purgative, such as castor oil or syrup of senna. 1. The ground bark is exhausted by heating with water on a water bath for an hour, the decoction is cooled, milk of lime is added in excess, the mixture filtered, water being added to the precipitate to wash out the alkaloid, the wash- ings added to the filtrate, the filtrate neutralized with dilute sulphuric acid and again filtered. It may be taken in this form, after adding about a gram of tannin, or the neutral- ized filtrate may be evaporated on a water bath until nearly solid, and then extracted with 70 per cent, alcohol; this is then filtered and subsequently evaporated to a dry extract which is approximately equal to pelletierin. 364 PHARMACOPEIA AND PHYSICIAN. Of 33 cases treated in this way, the entire para- site, including the head, was removed in 29 cases. Failure in some cases is to be attributed to the head being securely protected by the folds of the mucous membrane. It is somewhat significant that the many for- mulas which have acquired some reputation in the treatment of tape worm contain pomegranate bark. The following taken from Osier is almost identical with a formula which has been held as a proprietary by a southern firm for a great many years, among whose patrons it enjoys a consider- able reputation : R. Granati 3iv 15 1 Pepo *i 30 1 Ergot® pulveris 3i 4| Aqu® bull f§x 300 1 An infusion is directed to be made [better a decoction], from which is formed an emulsion, by adding: Oleoresina aspiaii 3i 4| Olei tiglii mii j 12 Acaci® q. s. The oleoresin of aspidium may be given as an emulsion or in capsules, or it may be combined with teniafuges, somewhat after the formula given above. Pumpkin seeds are harmless and may be given either in substance or in the form of a decoction, using an ounce or more of the bruised seed. Of the other official substances that have been used to assist in expelling tenia it will suffice to enumerate : ether, chloroform, rectified oil of tur- pentine, napthalen and thymol. These are all comparatively active drugs and must, therefore, be used with caution. PARASITICIDES , ANTIGOyORRHEICS. 365 ANTIGONORRHEICS. The title antigonorrheics would appear to sug- gest that we have medicaments that have a spe- cific action on gonorrhea, or the causative factor of that disease, instead of representing, as it really does, a somewhat meaningless array of substances that have been used more or less empirically as remedies for gonorrhea. The name gonorrhea should properly be re- served for the acute, contagious inflammation of mucous membranes caused by a specific organism, the gonococcus of Neisser. In an even more re- stricted sense it is now frequently applied to the specific inflammation caused by that micro-organ- ism in the male urethra. Prior to the discovery of the ' gonococcus, by IsTeisser, in 1879. there was probably no one com- mon disease about which there existed such widely varying theories and opinions, and certain it is that no known disease has been so persistently and so widely maltreated. From the time of the early Greeks and of the Romans the treatment of gonorrhea appears to have been relegated to the incompetent, the char- latan and the quack, and it may be safely asserted that no one disease, with the possible exception of syphilis, has been the direct, or the indirect, cause of more misery, more suffering and more untimely deaths because of this neglect and maltreatment. Recognizing the seriousness of the disorder it would he futile to give suggestions for exhaustive treatment, and practicallv the only apology that we have to offer for introducing even a mention of the disease, and of some of the official remedies 306 PHARMACOPEIA AND PHYSICIAN. that may be of use in its treatment, is to be found m the fact that victims of this disorder are even now subjects for neglect and malpractice. Evi- dent proof of this can be found in almost any one of the daily papers which regularly advertise spe- cific cures for all forms and kinds of urethral dis- charges. The heinousness of this practice, and the really far-reaching and serious consequences of the prac- tice in its ultimate results have not as yet been properly appreciated even by such members of the medical profession as should be more thoroughly well informed. This is, in a measure, evidenced by the recently published statement, made by a prominent genito-urinary specialist, that he fre- quently uses and recommends a popularly adver- tised nostrum, the manufacturers of which delib- erately mislead the layman into believing that he can be cured in 48 hours. As suggested above, the treatment of gonorrhea is not by any means the simple procedure that might be wished for and even the differentiation of true gonorrhea from a non-specific inflammation is one that requires more than ordinary skill and experience, and should, wherever possible, be en- trusted to a safe and conscientious specialist, who not alone has the interest of the patient in mind, but who will also attempt, so far as in him lies, to prevent the spread of the infection by impressing on the patient the advisability of observing certain necessary rules of cleanliness, decency and ab- stinence. Using the name, gonorrhea, in its most re- stricted sense, as applying only to the specific urethritis in the male, we may consider this as a PARASITICIDES, AATIGOXORRHEICS. 367 type, and recount some of the suggestions for treatment that have been made in connection with it. This type of gonorrhea is said to be acute, sub- acute, or chronic, according to the stage of the in- flammatory process, and it may involve the an- terior urethra alone or include, by continuity, the posterior urethra. The generally accepted routine treatment is to use only a mild astringent and antiseptic local application for the first or acute stage, to supple- ment this with the internal use of diuretics, of a terebinthinate or resinous nature, in the subacute or secondary stage, and to use more active astrin- gents and antiseptics as local applications in the chronic stage of the disease. It will he noted by this that what is usually re- ferred to as an antigonorrheic is in reality but a diuretic, an antiseptic or an astringent. Of the several official drugs and preparations that have been found to be more particularly use- ful in these several stages of the disease, we may enumerate : Potassii Perm anga nas. — U. S. — This is rec- ommended to he used, as an irrigation, in very di- lute solutions (1-2,000 to 1-6,000). Argenti ISTitras. — U. S.— This was formerly quite popular, in very dilute solutions, but has fallen into disuse and is now frequently substituted by one or the other of the non-official so-called or- ganic silver salts. These latter preparations, while unduly numerous, are usually expensive and the more active of them are inexpressibly filthy. A satisfactory and apparently efficient substi- tute for the several silver preparations has been 368 PHARMACOPEIA AND PHYSICIAN. found in silver iodid. Drs. Siter and Uhle 2 have reported a series of eases in which this preparation was used, in the form of an emulsion of the freshly prepared silver iodid, with excellent results. A preparation such as was used by Drs. Siter and Uhle may be prepared by any pharmacist, as follows : Argenti nitratis Potassii iodidi, aa gr. sxxiii 2 [2 Mucilago chondri N. F f.3vi 25 1 Aquae dest. q. s. ad f.Jiii 100 [ M. Sig. : Use as an injection. The best method of preparing a finely divided precipitate is to dissolve the potassium iodid in all of the water and add the crystals of silver nitrate gradually, shaking well after each addition; when the silver nitrate is dissolved, add the mucilage and shake thoroughly once more. The resulting mixture will represent approx- imately 3 per cent, of silver iodid. The strength may be increased or decreased as desired. If pre- pared in this w r ay, the weaker mixtures will require a correspondingly smaller amount of mucilage to hold the powder in suspension and mixtures below 1 per cent, may be dispensed without the addition of any foreign material. Of the drugs that are frequently used for inter- nal administration in the second or sub-acute stage of the disease the Pharmacopeia includes, in the order of their present popularity : Oleum Santali. — U. S. — Oil of Santal. or oil of sandalwood, is a volatile oil distilled from the wood of Santalum album. The Pharmacopeia di- 2. University of Pennsylvania Med. Bull., May, 1905. PARASITICIDES, ANTIUONORRHEICS. 369 rects that this oil contain not less than 90 per cent, of santalol. This requirement is readily met by the better grades of oil of santal now on the market, so that there is little or no need to resort to proprietary specialties containing, or purporting to contain, true oil of santal. Average Dose: 0.5 c.c. (8 minims). Copaiba. — U. S. — Copaiba, balsam of copaiba, as it is more popularly called, is derived from one or more South American species of copaiba. It was introduced into Europe by the Portuguese, during the latter half of the seventeenth century, and has long enjoyed the reputation of being of especial use in connection with specific urethritis in the male. Average Dose: 1 c.c. (15 minims). Oleum Copaiba. — U. S. — Oil of Copaiba is offi- cially described as a volatile oil distilled from copaiba. Average Dose: 0.5 c.c. (8 minims). OLEOBESiNiR Cubebje. — U. S. — Oleoresin of Cu- beb represents the alcohol soluble portion of the dried, unripe, fruit of Piper Cubeba. Average Dose: 0.5 c.c. (7)4 grains). Oleum Cubeba. — U. S. — Oil of Cubeb is a vol- atile oil distilled from cubeb. Average Dose: 0.5 c.c. (8 minims). Of the more active astringents that are used in the third, or chronic stage of gonorrhea, in the male, and form such a prominent part in the treat- ment of the more common form of gonorrhea in the female, we may enumerate: Zracr Sulphas.— IT. S. — Zinc Sulphate. Zinci Acetas. — TJ. S.— Zinc Acetate. 370 PHARMACOPEIA AS D PHYSICIAN. Zinci Chloridtjm. — U. S. — Zinc Chlorid. Zinci Piienolsulphonas. — U. S. — Zinc Phe- nolsulphonate. Alumen. — U. S. — Alum. Acidum Tannicum. — U. S. — Tannic Acid. Argenti Nitras.- — U. S. — Silver Nitrate. These several astringents, with or without the addition of well-known antiseptics, such as boric acid, phenol, thymol, glycerin, and the several combinations or preparations of them, practically constitute all that is necessary in the treatment of the most persistent of the chronic forms of gon- orrhea. CHAPTER XVI. SUBSTANCES USED AS VEHICLES. The great majority of physicians pay all too lit- tle attention to the art of rendering their prescrip- tions pleasing alike to the eye and to the palate. Even in medical schools, if the matter is considered at all, it is usually deemed sufficient to instruct the student to give the mixture a sweet taste, by the addition of syrup, or a distinctive aroma by the addition of one or the other official medicated waters, with little regard for individual taste or the nature of the mixture. In the matter of ap- pearance it is commonly considered quite sufficient to avoid the inky mixtures produced by the addi- tion of iron compounds to preparations containing tannin or tannin-like substances. Prom the point of view of the patient it is safe to say that the appearance of a mixture is often of even greater importance than the taste, not alone in so far as it concerns the individual preference of the patient, but even to the extent of affecting the absorption and the subsequent assimilation of the medicine, since we know that the digestive se- cretions are stimulated by tempting looking sub- stances and are inhibited by those which appear disgusting. In the case of women and children tlie subjects of flavoring and coloring are of much more importance than with men. While the aver- age physician will, no doubt, rightly consider that this subject does not deserve very extensive study on his part, he must admit that the observance of PHARMACOPEIA AND PHYSICIAN. 372 a few easily acquired rules may be well worth re- membering. Unlike the question of ready-made formulas for a great variety of conditions demanding individ- ual consideration, there is no reason why flavoring and coloring should not be reduced to the very simplest forms and used as a routine whenever the mixture admits of it. When considering a subject that is so far-reach- ing and varied as this must be, it will, of course, be evident that the discussion of the several mat- ters can not be taken up in detail, but rnugt of ne- cessity be more in the nature of suggestions for ob- servation and study. With the wealth of material that is available, by the use of the official aro- matics and diluents, it should be a comparatively easy matter for a plrysician to become thoroughly familiar with the properties and possible uses of at least several of these preparations and by judicious combination to produce not alone a variety of mix- tures, but, also, to impart to them an individual- ity in which he may well take pride. Many of the comparatively tasteless substances require but the addition of some mildly aromatic solvent or diluent, such as the aromatic medicated waters. Substances that are more acrid, bitter or saline in taste may be masked by the addition of a small amount of syrup to the aromatic, or by the addition of a preparation containing glvcyrrhizin, like the now official elixir adjuvans. Nauseous bitters are best masked with strong aromatics and syrup. The simple but persistent bitters, such as quinin and strychnin, are agreeably modified by such an aromatic as tincture of sweet orange peel, wine and sufficient syrup to suggest sweetness. As SUBSTANCES USED AS VEHICLES. 373 an example of such, a preparation we may mention the bitter wine of iron, which will be appreciated if one will but taste this really elegant prepara- tion. MEDICATED WATERS. The most simple, and, therefore, the most read- ily available of the official diluents or vehicles are the aromatic, medicated waters. They are partic- ularly well adapted for dissolving such compara- tively mild tasting substances as potassium citrate, sodium benzoate, sodium salicylate, morphin sul- phate and antipyrin. One of the most pleasant of these preparations is : Aqua Amygdala Amar^e. — U. S. — Bitter al- mond water. This contains about 0.1 per cent, of oil of bitter almond, and appears to be particu- larly adapted for use with sedative expectorants such as codein sulphate. Average Dose: 4 c.c. (Ifluidram). The following are particularly well adapted for use with children : Aqua Anisi. — IT. S. — Anise Water, and Aqua Fceniculi. — IT. S. — Fennel Water. They contain about 0.2 per cent, of the respective vola- tile oils and have long been popular as correctives or diluents for medicines such as fever mixtures and mild anti-diarrhea mixtures, designed pri- marily for children. Average Dose of either of the above: 16 c.c. (4 fluidrams) . Another aromatic water that has met with con- siderable use is : Aqua Cienamomi. — IT. S. — Cinnamon Water also represents approximately 0.2 per cent, of the 374 PHARMACOPEIA AND PHYSICIAN. volatile oil and, as a flavor, is sometimes pre- ferred. Average Dose: 16 c.c. (4 fluidrams). By far the most popular of the aromatic waters are: Aquje Menth2E Piperita. — U. S. — Pepper- mint Water, and Aquje Menthje Yiridis. — U. S. — Spearmint Water. These, like the preceding, are simple solu- tions of volatile oils in water and represent ap- proximately 0.2 per cent, of their respective vola- tile oils. Average Dose of either : 16 c.c. (4 fluidrams) . Peppermint water, or spearmint water, is partic- ularly well adapted for use with the mild alkalies, such as potassium bicarbonate or sodium bicarbon- ate, or mixtures of these with other soluble salts. The efficiency of solutions of the alkaline bicar- bonates may be usually enhanced by the addition of a simple bitter, such as tincture of nux vomica or tincture of calumba. Simple solutions, even such as contain a small addition of a bitter substance, should be directed to be filtered, as this adds materially to the appear- ance of the mixture and thus enhances its palat- ability and efficiency. When a vehicle having more pronounced char- acteristics is desired the official aromatic elixir will probably serve to meet more possible indications than any one other preparation. It may itself be varied by the addition of the fluid extract of gly- cyrrhiza, as in the official elixir adjuvans. or by the addition of one of the official spirits, syrups, aro- matic tinctures or simple wines. Aromatic elixir is particularly useful in connec- SUBSTANCES USED AS VEHICLES. 375 tion with the scale salts of iron, the bitter alka- loids, and also with the soluble iodids and bromids ; with the latter, however, the stimulating effect of the contained alcohol should not be lost sight of. The following are among the preparations that will be found to be of use in connection with the possible modifications of the simple elixir or other desirable vehicles : Elixir Aromatxcum. — U. S. — Aromatic Elixir is practically a. solution of a mixture of the oils of orange peel, lemon, coriander and anise in 25 per cent, alcohol, containing about 38 per cent, of syrup. The resulting preparation is not alone strongly aromatic, but is also sufficiently dense to hold finely divided substances well in suspension, while the alcohol content is not sufficient to be ob- jectionable in the ordinary doses. Elixir Ad ju vans. — U. S. — Adjuvant elixir. This is a simple mixture of 12 parts of fluidextract of glycyrrhiza with 88 parts of aromatic elixir, and is particularly well adapted for masking acrid, bitter or saline materials. The contained glycyr- rhizin not being soluble in acid solutions, the prep- aration is obviously not suited for use with diluted acids or acid salts. The official spirits that may be used as additions to aromatic elixirs or as correctives to other alco- holic or hydro-alcoholic solutions are : Spiritits Anisi.— U. S.- — Spirit of Anise con- tains 10 per cent, of oil of anise in alcohol. Average Dose: 4 c.c .(1 fluidram). Spiritus Amtgdalie Amarje. — U. S. — Spirit of Bitter Almonds contains 10 per cent, of oil of bitter almond in alcohol, and is the most potent of the official spirits. It is markedly aromatic and a very 370 PHARMACOPEIA AND PHYSICIAN. small quantity usually suffices to impart a dis- tinctive almond odor and taste. Average Dose: 0.5 c.c. (8 minims). Spiritus Cinnamomi. — U. S. — Spirit of Cinna- mon contains 10 per cent, of oil of cinnamon. Average Dose: 2 c.c. (30 minims). Spiritus Gaultheri^. — U. S. — Spirit of Gaul- tlieria is a useful preparation for cases in which the patient appears to have a predilection for teaberry or wintergreen. This preparation imparts a dis- tinctive odor and taste and should be used with caution, as it appears to be objectionable to many people. It represents 10 per cent, of oil of gaul- theria. Average Dose: 2 c.c. (30 minims). Spiritus Mentha Piperita. — U. S. — Spirit of Peppermint and Spiritus Mentha Yiridis. — U. S. — Spirit of Spearmint, in addition to containing 10 per cent, of the respective volatile oils also represent the al- cohol-soluble portion of 1 per cent, of the respective dry crude drug, which imparts to them a dis- tinctive yellowish-green color. Average Dose (either) : 2 c.c. (30 minims). The aromatic tinctures that are particularly useful for adding distinctive characteristics to liquid mixtures are : Tinctura Aurantii Dulcis. — IT. S. — Tincture of Sweet Orange Peel. This preparation is directed to be made from the fresh peel and represents ap- proximately 50 per cent, of the crude drug. It is a delicate but efficient aromatic and is useful in connection with any of the hydro-alcoholic mix- tures. Average Dose: 4 c.c. (1 fluidram). SUBSTANCES USED AS VEHICLES. 377 Tinctura Cardamomi. — U. S. — Tincture of Cardamom represents 20 per cent, of cardamom in diluted alcohol. Average Dose: 4 c.c. (1 fluidram). Tinctura Cardamomi Composita. — U. S. — Compound Tincture of Cardamom represents 2.5 parts each of cardamom and Saigon cinnamon, 1 part of caraway, 0.5 parts of cochineal and 5 parts of glycerin in sufficient diluted alcohol to make 100 parts. Average Dose: 4 c.c. (1 fluidram). Tinctura Lavandula Composita. — IT. S. — Compound Tincture of Lavender consists of a mix- ture of 0.8 parts of oil of lavender flowers and 0.2 parts of oil of rosemary in 75 per cent, alcohol, which is used to exhaust 2 parts of Saigon cinna- mon, 0.5 part of cloves, 1 part of nutmeg and 1 part of red saunders. The possible uses of this preparation are prob- ably best illustrated by the official solution of potassium arsenite, which is flavored and at the same time colored by the use of 3 per cent, of this tincture. Average Dose: 2 c.c. (30 minims). Tinctura Vaxillae. — IT. S. — Tincture of Ya- nilla represents 10 per cent, of vanilla in 65 per cent, alcohol and is sweetened by the addition of 20 per cent., by weight, of sugar. The official simple wines are : Yinum Album. — IT. S. — White Wine. This is an alcoholic liquid, made by fermenting the juice of fresh grapes, the fruit of Vitis vinifera, and usually contains about 10 per cent, of alcohol. White wine constitutes an excellent vehicle for a number of acrid or bitter substances, and is par- 378 PHARMACOPEIA AND PHYSICIAN. ticularly useful as an addition to the official aro- matic elixir. If from 10 to 25 per cent, of white wine be added to aromatic elixir it will impart to the latter a distinctive and generally agreeable odor and taste. Vinum Rubrum. — TJ. S. — Red Wine is an alco- holic liquid that is made by fermenting the juice of fresh, red-colored grapes, the fruit of Vitis vinifera, in the presence of their skins, and sub- jected to the usual cellar treatment for fining and aging. The official syrups that are generally well known or widely used as diluents, correctives or vehicles are : Syrupus Acidi Citrici. — U. S. — Syrup of Cit- ric Acid. This is a slightly acid syrup, flavored with tincture of fresh lemon peel, and is useful in connection with the aqueous solutions of the alka- line salts of organic acids, such as potassium citrate. Syrupus Aurantii. — U. S. — Syrup of Orange also contains a trace of citric acid and has a pleas- ant acidulous taste. It is frequently used in place of the syrup of citric acid and is preferred by many. Syrupus Pruni Virginian^.- — -TJ. S. — Syrup of Wild Cherry, while it represents the aqueous ex- tractive of 15 parts of wild cherry, is most largely used as a pleasant vehicle or as an addition to other diluents, particularly in connection with expec- torants. Average Dose: 4 c.c. (1 fluidram). Syrupus Tolutanus. — U. S. — Syrup of Tolu represents the water-soluble portion of 5 per cent, of tincture of tolu, and. like the preceding, is fre- SUBSTANCES USED AS VEHICLES. 379 quently used as a corrective to mixtures that are designed for use as expectorants. Average Dose: 16 c.c. (4 fluidrams). Syrupus Sarsaparilla Compositus. — U. S. — Compound Syrup of Sarsaparilla contains fluidex- tract of sarsaparilla, fluidextract of glycyrrhiza and fluidextract of senna, and is flavored with a mixture of the volatile oils of sassafras, anise and gaultheria. This preparation constitutes an interesting re- minder of the widespread use of sarsaparilla as a universal panacea almost a century ago, but it is now seldom used for any other purpose than as a vehicle. It is particularly useful for such acrid drugs as the soluble mercurial salts and the iodids and bromids. Average Dose: 16 c.c. (4 fluidrams). For use with immiscible liquids, for making emulsions and for suspending insoluble powders in aqueous solutions it is an almost universal prac- tice to use the official mucilage or gums. Mucilago Acacia. — U. S. — Mucilage of Aca- cia, containing 34 per cent, by weight of acacia, 33 per cent, of limewater and 33 per cent, of dis- tilled water, is probably the best known of these several preparations. It has a very wide field of usefulness, but as acacia is precipitated by alcohol is not useful in connection with strongly alcoholic liquids. The presence of limewater may prove to be a disturbing factor in connection with solutions of the alkaloids, and here the mucilage may readily be substituted by the syrup. Syrupus Acacia. — TJ. S. — This represents 10 parts of acacia in a moderately heavy syrup. Mucilago Tragacaytha. — U. S. — Mucilage of ;80 PHARMACOPEIA ART) PHYSICIAN. Tragacanth contains 6 parts of tragacanth, 18 parts of glycerin and sufficient water to make 100 parts. This preparation is particularly useful in connec- tion with alcoholic liquids and is very widely used for suspending the content of resinous tinctures in aqueous mixtures. Another preparation that is quite extensively used to mask acrid, bitter or otherwise disagree- able drugs is the recently admitted Extractum Marti. — TJ. S. — Extract of Malt occurs as a semi-solid extract, having the consis- tency of thick honey, and is itself considered to be nutritive, tonic and laxative. It has been used quite extensively, particularly in connection with several widely used proprietary preparations, as a vehicle for cod-liver oil, cascara sagrada and the bitter alkaloids like quinin and strychnin. Average Dose: 16 c.c. (4 fluidrams). SUGGESTIVE COLORING. The subject of coloring is a much simpler one than is that of flavoring, but it is of almost equal importance, if we are to judge by the practices that have been followed by manufacturers of elegant proprietaries for upward of a quarter of a cen- tury. Coloring agents are primarily divided into such as are useful with alkaline and neutral substances and such as are useful with dilute solutions of the official acids and acid salts. For those of the first class, preparations con- taining carmin or cochineal, for red, and glycyr- rhizin for brown are readily available. For the so- lutions of acids and acid salts, however, neither of these substances would answer, as they are both SUBSTANCES USED AS VEHICLES. 381 precipitated by acids, and we have recourse, there- fore, to cudbear for the red and caramel for the brown. Taking the official aromatic elixir as a type, this may be colored a bright red by the addition of from 10 to 20 per cent, of the compound tincture of cardamom, containing cochineal, or it may be given an equally bright red color by the addition of 1 per cent, of the Tincture of Cudbear of the National Formulary. Cudbear is the source of the bright red color that is so common in pro- prietary preparations, and as cudbear itself has no known medicinal properties, apart from the pleas- ing suggestiveness of the resulting preparation, we must naturally conclude that the manufacturers of proprietary preparations have succeeded in im- pressing not alone the patient, but, in many cases at least, the physician also, by the judicious use of pretty colors. The use of caramel (burnt sugar), is too well known to need further comment, apart from the fact that the National Formulary contains a for- mula for a compound tincture of cudbear which contains 10 per cent, of caramel and will be found useful when a brownish-red preparation is de- sired. A very pleasing golden-yellow mixture that ap- pears to be fairly stable with either acid or alka- line solutions may be obtained by adding 1 per cent, or even less of the now official tincture of hydrastis. This preparation, though made with 65 per cent, alcohol, mixes readily with the official elixir, but precipitates slightly when added to aqueous solutions, and they should, therefore, be directed to be filtered before being dispensed. CHAPTER XVII. THE NATIONAL FORMULARY AND THE USE OP EXTRAPHARMA COPET AT; SUBSTANCES. An extended review of the application and the uses of pharmacopeial articles would be incomplete without some discussion of permissible extra- pharmacopeial substances, and at least a passing reference to that most legitimate of all sources of unofficial preparations — the National Formu- lary. To appreciate more thoroughly the rise and the need of authoritative works of reference on extra- pharmacopeial preparations we must remember that the remedies which have been, and which properly should be, included in the National Phar- macopeia constitute but a very limited portion of the possible resources of medical men of the pres- ent day, and are practically confined to those well- known drugs and preparations that are generally used in all parts of the country, and may, there- fore, be considered as being thoroughly well estab- lished. Despite the fact that a medical practitioner who is thoroughly well acquainted with the established, or official, materia medica would be in a position to meet all possible physiologic as well as thera- peutic indications, so far as known, there is no gainsaying the fact, that there can be no progress without experimentation, and experimentation in THE NATIONAL FORMULARY. 383 the field of materia medica implies the use of new remedies in comparatively well understood patho- logic conditions, or the use of well-known or other- wise well established remedies in conditions that are less well understood. With the gradual increase of our knowledge of the physiologic action and the limitations of medic- inal substances there is a correspondingly decreas- ing need for the empiric use or the haphazard ex- perimentation with drugs and other therapeutically active substances. On the other hand, it must also be remembered that physiologic indications, as we understand or interpret them, at the present time, do not fully represent the therapeutic uses and the limitations of medicinal substances in the diseased human organism. Bearing in mind, then, the imperfect state of our knowledge concerning the normal functions of the several organs of the human body, the possible irregularities or diseases and the treatment of these irregularities with the more or less imperfect mate- rials at our command, and it may be added also, the multifarious demands on the general prac- titioner in the daily routine of his practice, no reasonable individual can possibly object to the use of safe and well-understood substances that have been demonstrated to possess medicinal virtues, though they have not been admitted to the roll of more thoroughly established articles represented by the Pharmacopeia. Here, however, differences of opinion will arise as to what constitutes a safe and well-understood medicinal substance. Since it is impossible for a medicinally active substance to be potent only for good and to be innocuous as far as deleterious results are concerned, we must modify 384 PHARMACOPEIA AX D PHiSICIAX. the first part of our requirement and limit it to articles, the action and uses of which have been established. While this requirement would undoubtedly con- stitute a reasonable and rational safeguard, it will be difficult to limit ourselves to it too strictly. The reasons for this will become more apparent when we remember that such a comparatively simple drug as squill, which has been in continuous use for hundreds of years, even now is not well under- stood, either chemically or physiologically, and that digitalis, a drug that has been studied by the lead- ing men in the medical profession almost continu- ously for half a century, still presents problems to the clinician as well as to the pharmacologist, that may require years, if not decades, of added work to solve. When we realize how little positive knowledge we possess of the action, uses and limitations of drugs and medicinal preparations, that have been in con- tinued use for a long period of time, we begin to suspect that many, if not all, of the positive claims that are now being made in connection with new drugs and complicated synthetic chemicals, may, after more careful observations, be found to be far from correct. The secondary or so-called untoward effects of many drugs and preparations are so insidious that much harm may be done before it becomes known that such untoward effects should be looked for. As an illustration of the harm that may result from the indiscriminate or too liberal use of new remedies, even of the comparatively few that ap- pear to have established themselves as permanent additions to our materia mediea, attention is THE NATIONAL FORMULARY. 385 directed to the harm that has been done, directly, as well as indirectly, by acetanilid. For over twenty years acetanilid was freely used, either in substance or in the form of various mixtures that are even now being marketed as pro- prietary nostrums. All of these preparations were presumed to be potent factors for good and innocu- ous so far as any deleterious results were con- cerned. Despite the fact that many physicians suspected that acetanilid was directly responsible for a long train of little-understood symptoms that occur as secondary complications from its excessive or con- tinued use, it is fair to presume that but few were prepared to assert that acetanilid was directly to blame for the many really serious complications, and even deaths, that have been reported during the past year or two. Of the other new remedies that are widely used, largely because manufacturers have asserted that they are free from possible injurious effects, we may refer to the widely used coal-tar hypnotics. Drugs of this kind are freely used by lay persons of all degrees of intelligence in the mistaken belief that they are safe and harmless. It is known, however, that all hypnotics conduce to the con- tinued use of sedative drugs and many are the direct cause of physical, mental and moral de- generacy. In addition to the possible harm that may result from the continued use of drugs of this type, it lias been repeatedly shown that the coal-tar hypnotics, despite their reputed harmlessness, have been the direct as well as the indirect cause, in many instances, of death. One more illustration of our overzealousness to 380 PHARMACOPEIA AND PHYSICIAN. believe the assertions of manufacturers, to our own discredit : A few years ago diacetylmorphin, better known by the proprietary name heroin, was being exploited as a perfectly safe and reliable sub- stitute for morphin. Heroin was reputed to pos- sess all of the good properties of morphin without any of its faults, and it was even heralded as a positive cure for the morphin habit. According to more recent reports, however, heroin is not devoid of the danger of inducing drug addiction, and, what is even worse, is latterly reported to conduce to a habit that is as persistent as the morphin habit itself. The experience that we have obtained from these now better imderstood and valuable remedies • should be sufficient to make us more cautious in the use of new drugs and chemicals that are ex- ploited by those whose only interest in them is purely commercial. The evident need in connection with the introduction of new drugs and chemicals is a less restricted dis- semination of information bearing on their un- toward results and shortcomings, so that unneces- sary repetition of disappointing and at times harm- ful experiences may be avoided. How imperative is this need for greater publicity in connection with newer remedies is well illustrated by the vol- umes on new remedies that have been published during the past two decades. If we review one of the volumes that has been published ten or more years ago we find hundreds of highly recommended substances that are now out of use, despite the fact that no derogatory report can be found in the pages of current medical journals. That some really vital reason for the disappearance of these numer- THE NATIONAL FORMULARY. 387 ous substances must have existed is evident, but the present method of eliminating such new reme- dies is objectionable as not only slow but full of possible harm to our patients. The publication of the proposed Handbook on Hew and Non-official Kemedies by the American Medical Association, through its Council on Phar- macy and Chemistry, will no doubt contribute materially to bring about a better understanding and a more rapid elimination of the numerous remedies of uncertain value and composition that are now being offered. In this connection it is fair to suppose that manufacturers, who will be given the advantage of added publicity for the de- sirable properties of their several preparations, will not oppose free and impartial discussion of the shortcomings and the limitations of these prepa- rations. Drugs and chemicals of original and meritorious character constitute but one of several classes of extrapharmacopeial articles that merit careful con- sideration. A much larger class, and one whose use has been accompanied by even greater abuses, consists of mixtures of more or less well-known sub- stances whose preparation requires but ordinary pharmaceutical skill and which may be prepared quite as satisfactorily by the retail pharmacist as by the large manufacturer. The allegations that are usually made for mixtures of this kind, when exploited as proprietary products, are frequently misleading, due to the direct or implied mis- statements that are made in connection with the advertising matter put out by their manufacturers. Another cause for the present situation is the quite natural assumption of these lay manufac- 388 PHARMACOPEIA AND PHYSICIAN. turers that the simple admixture of two or more well-known substances constitutes a discovery, and that the making of such a “discovery,” or perhaps only the rediscovery of such a discover}’, should entitle the individual making it to certain perma- nent privileges in the form of absolute control of the particular combination, and should further per- mit him to exact such emoluments or profits as he sees fit. Quite apart from the absurdity of the claim of proprietorship in each mixture is the assumption that because such a mixture is made by one certain individual or firm it must be invested with cer- tain new or extraordinary properties and will, therefore, be superior, and will meet a variety of indications foreign, to the same mixture when compounded by some other presumably less skillful persons. How far-reaching the further unre- stricted progress of this species of proprietorship might become is indicated by the fact that at the present time there are over 30,000 distinct prepa- rations, and that the articles that are official in the Pharmacopeia of the United States alone would offer further possibilities of untold thousands of similar “original” mixtures. While it is reasonable to suppose that one manu- facturer may possibly acquire a certain amount of skill in the combination of certain well-known ingredients, or may be in position to exercise greater care in the selection of the constituent materials, these assertions and claims are foreign to the ques- tion of proprietorship and may be conceded when such facts are actually demonstrated. Among the factors that have contributed to a more reasonable view of proprietorship in medicinal THE NATIONAL FORMULARY. 389 compounds are the National Formulary and other books of its particular type. It is more particularly due to the general recognition that has been ac- corded the National Formulary as an authoritative standard for unofficial preparations that we at the present time are better able to differentiate between the reasonable announcements that are made by reputable manufacturers and the bold claims of absolute proprietorship, based on pretended priority of discovery, made by manufacturers of question- able nostrums. That the use of well-established formulae, apart from those contained in the Pharmacopeia, is not a recent one is well illustrated by the natural se- quence and the evolution of well-known formularies in this country. The earliest of these, “Formulae Selectae, or a Collection of Prescriptions of Eminent Physi- cians,” was published by P. Donaldson, New York, in 1818, two years before the first edition of the Pharmacopeia of the United States was published in Boston. From the preface of this early formulary it ap- pears that its publisher fully appreciated the limi- tations and the needs of popular formulae and the contents of the 'book shows that not a few of the problems that confronted the medical practitioners of that early date are still with us, though changed somewhat in character. Tli is formulary is particularly interesting in that it gives us a fair representation of the develop- ment of the science of medicine at that time. Tn connection with the claims made for proprietor- ship in medicinal compounds it may be interesting to mention that among the numerous formulae for 390 PHARMACOPEIA AND PHYSICIAN. “patent medicines/’ mostly of English and Dutch origin, mentioned in this book, there are several of the then popular nostrums made in America. Under tire title “Connecticut Pill” we find a formula that “is believed to be the composition of the celebrated Lee’s pill.” This, it may be added, is reputed to have been the first medicine patented in the United States, and certainly was the direct cause of no inconsiderable amount of friction in the Connecticut State Medical Society. One quotation from the p ref ace illustrates the keen appreciation that its author had of the needs and the limitations of the several authoritative works of reference. He says : “A recipe may have reputation and deserved celebrity and yet not find a place among official preparations, which should be few in number and retrenched of everything that could be deemed superfluous.” The next formulary, in point of time, was that usually referred to as “Ellis’ Medical Formulary.” This book was originally compiled by Benjamin Ellis, a young physician of Philadelphia, who had attained some local celebrity as the professor of materia medica in the Philadelphia College of Pharmacy. The first edition of this book appears to have been published in 1828; it was followed by a sec- ond in 1829 and a third edition in 1831. The continued popularity of this formulary, even after its } 7 oung compiler’s early death in 1831, led to its repeated revision and republication. Several of these editions, including the eighth and ninth, were edited by Dr. S. G. Morton. The tenth and eleventh editions, appearing in 1854 and 1864 re- spectivelv. were edited by Dr. E. P. Thomas, and THE NATIONAL FORMULARY. 391 a twelfth edition, published in 1869, was edited by Dr. Albert H. Smith. Ellis’ formulary was essentially a compilation of prescriptions derived from the writings of emi- nent physicians in America and Europe, and the numerous editions of the book no doubt contributed materially to the continuance of the still existing practice of copying verbatim the prescription of some one individual for all or nearly all affections of a certain type. The popularity of Ellis’ formu- lary led to the compilation of a number of more or less original books of popular prescriptions and also to the republication of similar collections from England and the Continent of Europe. The popularity accorded to the prescriptions of foreign physicians led to a demand for prepara- tions official in the corresponding pharmacopeias of foreign countries. This demand was met by the publication of an American edition of Mayne’s Dispensatory, revised by Dr. R. Egelsfield Grif- fiths. This book was further augmented in 1850 by the publication of Griffith’s Universal Formu- lary, which, as the name indicates, was compre- hensive indeed. A second edition of the Universal Formulary, edited by Dr. Robert P. Thomas, was published in 1854. This edition appears to have been frequently reprinted, but the book was not issued in a revised form until 1873, when the third edition, edited by Prof. John M. Maisch, was published. This third edition includes a note- worthy suggestion of the evolution of our present day, so-called ethical proprietary medicines, the forerunners of which are to be found in the elixirs, or, perhaps more correctly, the cordial elixirs, which were so abused during the decade imme- 302 PHARMACOPEIA AM) PHYSICIAN. diately following 1870. At that time certain manu- facturers made use of the fashion that seemed to he in vogue of presenting every possible, as well as impossible, formula or combination in the form of an elixir. As an important development we have the Na- tional Formulary, published by authority of the American Pharmaceutical Association. The his- tory of this volume dates back to 1870, when a committee on unofficial formulae was appointed by the American Pharmaceutical Association. Little of practical value was accomplished, however, and the several reports, that were made never at- tained popularity, because they were buried in the official reports of the proceedings of the asso- ciation. After the publication of the Pharmacopeia of 1880 another concerted attempt was made by the American Pharmaceutical Association to compile an unofficial formulary. Under the able leadership of the late Dr. Charles Rice, of New York, a committee presented “a preliminary draft of a national formulary”, in 1886 and was able to issue the completed book in 1888. The sec- ond edition, under the editorship of C. Lewis Diehl, the present chairman of the committee on National Formulary of the American Pharmaceuti- cal Association, was published in 1896. and the third (1906) edition, or the second revision, has just been published. The formulae that are contained in the 211 pages of this last edition may be divided into groups consisting of : 1. Formulae from former editions of the United States Pharmacopeia. These have been gathered THE NATIONAL FORMULARY. 393 together in the form of an appendix to the Na- tional Formulary and are thus readily available for easy reference. 2. Formula? official in foreign pharmacopeias which have been popularized to some extent in this country through medical literature, but not suffi- ciently widely used to warrant their being included in the national Pharmacopeia. Of the many preparations of this type it will suffice to enumerate such comparatively well-known articles as Caffein Sodio-Salicylate, Ferrated Ex- tract of Apples, Pectoral Species, Laxative Species, Spirit of Formic Acid and Ethereal Tincture of Ferric Chloric!, all of them official in the German pharmacopeia. 3. Formulae introduced by prominent medical men or teachers that are either of comparatively recent origin or of restricted use. This class of formulae is perhaps best illustrated by the dermatologic pastes recommended by Lassar and Unna, for which a number of type formulae are included. Among other formulae that may properly come under this heading are such com- paratively well-known empiric preparations as Do- bell’s Solution, Loomis’ Diarrhea Mixture and Squibb’s Rhubarb Mixture. 4. Formulae representing present-day survivals of the old-time “patent medicines.” This class, although no longer numerous, is represented by such well-known titles as Turling- ton’s Balsam, Dalby’s Carminative, Bateman’s Pectoral Drops and Godfrey’s Cordial. 5. Formulae that may be considered to repre- sent imitations of well-known nostrums, or so- called ethical proprietary remedies. 394 PHARMACOPEIA AND PHYSICIAN . As noted before, this is a class about which there exists an honest difference of opinion. When we remember, however, that the most meritorious of these several nostrums represent very little that is original or novel, most often having been appro- priated from the prescriptions of well-known phy- sicians, and that the claims that are made in con- nection with many of them are based largely on extravagance and even deception, the propriety of using supposed imitations of any of them presents itself to us in quite a different light. To illustrate how very little originality is repre- sented by the average proprietary medicine and how, in not a few cases, the discoverer of the so- called new remedy has simply succeeded in dis- guising an old and well- kn own formula by impart- ing to it a new flavor, giving it some new color and conferring on it a new name, we refer to the fol- lowing formulas contained in this late edition of the National Formulary : The formula for “Alkaline Antiseptic” produces a preparation that is suggestive of the widely ad- vertised proprietary “Glyco-Thymoline.” From a therapeutic point of view this formula is evidently based on the old and widely used formula for “Compound Solution of Sodium Borate” — Do- bell’s Solution — the only evident difference being the substitution of the aromatic antiseptics for the “disagreeable” carbolic acid and imparting to the solution a characteristic color. In the National Formulary the formula for “Chloral and Brornid Compound” is strongly sug- gestive of “Bromidia,” but it also calls to mind the composition of the very much older and well- known English formulae for chloroform anodyne. THE NATIONAL FORMULARY. 395 chlor-anodyne and chlorodyne. The xlmerican “dis- coverer/’ it is true, has substituted for the compara- tively safe chloroform a huge dose of hydrated chloral and calls the resulting mixture a safe and harmless one, “the hypnotic par excellence.” Aside from the manifest untruths that are to be found in the advertising matter put out by the concern manufacturing Bromidia, and the pharmaceutical “knack” in preparing it, there is nothing original or novel to be recorded in connection with it. The Compound Digestive Elixir recalls the still widely used Elixir of Lactopeptine, which, apart from its pretty red color and admittedly pleasing taste, and enjoying great popularity as a general adjuvant, has little to recommend it therapeutic- ally. What is true of these preparations is also true of nearly all this class of mixtures that are now being exploited and sold as original preparations; they are original only in so far as they relate to the particular manufacturer or his individual ideas and represent nothing really new or original. The few examples enumerated above will also serve to indicate that in place of presenting form- ulae for imitations of proprietary remedies the Na- tional Formulary really reflects how the demands of medical practice are met by improved pharmacy, to which the manufacturers of proprietaries have contributed but little. Apart from the question of individual right in the formula or the composition of any particular preparation is the fact that practically all nostrums marketed through physicians are so sold, adver- tised, prescribed, labeled, etc., as to induce self- medication by the laity, and many of them are ad- vertised. at least indirectly, to the public. When 390 PHARMACOPEIA AND PHYSICIAN. we remember that many of these preparations rep- resent dangerously potent drugs and that all of them are a menace to the public health unless their use is intelligently directed, we must admit that as physicians we have been sadly remiss in our duty as guardians of the public "health in even allowing, (to say nothing of fostering), the present-day mul- tiplicity of objectionable nostrums. Even in connection with preparations that are otherwise unobjectionable it is possible to find really serious abuses for which we are directly re- sponsible. jSTot a few of the manufacturers of medicinal preparations have assumed the role of scientific investigators and attempt at least to pose as such before us and before the public. In ex- ploiting their wares, however, they commonly extol all of their virtues, but either minimize their dis- advantages or, more frequently, omit all mention of adverse criticism. We would instantly discredit any scientific investigator detected in such decep- tion, and if manufacturers continue to attempt to pose as scientific investigators we should, in jus- tice to ourselves, demand the same standards in the exploitation of new remedies that we do in scientific research, and above all we should insist that we ourselves are not misled by garbled and un- reliable reports of the wonderful cure-all proper- ties of a new remedy. We should also guard against the imposition of old and well-known drugs and combinations under fanciful or deceptive trade names and should pro- tect our patients, the pharmacists and ourselves against the evils of self-medication by always em- ploying the scientific titles in preference to the trade names for the article we use or prescribe. INDEX [Heavy-face figures indicate pages on which subjects are treated at greater length than on the other pages mentioned.] A. C. E. mixture, 206. Acetanilid, -50, 251, 252, 251, 257, 385. Acetate of lead, 150. Acetates of sodium and potas- sium, 317. Aeetparaphenetidin, 251. .Aeetphenetidin. 251 , 255. Acetum opii, 241. scilke, 231. Acid arsenous, 91. benzoic, IS. boric, 45. cinnamic, 18. erotonoleic, 337. lactic, 258. ricinoleic, 337. tartaric, 343. Aeidum arsenosum, 91. carbolicum, 26, 38 , 202. hydriodicum dilutum, 115. hydrochloricum, 59. hydrocyanicum dilutum, 233. hypophospliorosum, 99. nitricum, 182. phosphoricum, 98. salicylicum, 40 , 64, 6S. tannicum, 143 , 370. Aconite, 199, 297 . action of. 298. Aconitin, 189, 199, 200 , 299, 300 . amorphous, 299. Acorus calamus, 127. Adeps lanas hydrosus, .184. Adjuvant elixir, 375. Adrenalin, 158, 190, 303. vEther, 218 , 293. .Ethylis carbamas, 262. .Ethylis ehloridum, 217. Agurin, 313. Albuminate, Marfori’s, 73. Albuminates, metallic, 139. Albuminate of iron, 74 , 76. Alcohol. 31, 161 , 292. Alimentary canal, antisepsis of, 57. Alkaline antiseptic, 394. antiseptic tablet, 46. Alkalinity of blood, 317. Alkaloid of suprarenal gland, 156 , 190, 281. Alkaloids, precipitant of, 142. Aloes, 327. and iron pills, 77. Aloinum, 327. Alteratives, 104. Alum, 151, 152 , 370. as a gargle, 46. Aluminum sulphate, 152. American wormseed, 356. Amido-phenol, 257. Ammonol, 250. Ammonia, 256 , 315. Ammoniated glycyrrhizin, 234. Ammonii carbonas, 2:i5, 291. ehloridum, 226. iodidum, 116. salicylas, 6S. Ammonium acetate, 85. carbamate, 291. carbonate, 235, 254, 291, 292. chlorid, 27, 43, 226, 292. citrate, 87. preparations, 291. Amyl nitrite, 304. Amylene hydrate, 261. Amylis nitris, 304. Analgesics,' 237 , 260. Analgesin, 251. Anemia, S5, 94, 97, 103. Anesthesia, injections for local, 193. intraspinous injections for, . 104. Anesthetics, general, 204. local, 188. Angina pectoris, 303, 305. Anhvdromethylen citric acid, 316. Anilin, 257. colors, 48. Anise water, 373. Anodynes, 188 , 232. Anthelmintics, 65, 354, 362. Anthracene, 324. derivatives, 325. Anthrachinone, 326. 398 PHARMACOPEIA AND PHYSICIAN. Antifebrin, 250. Antigonorrheics, 353, 365. Antikamnia, 250. Antimony, £25. and potassium tartrate, 225. Antipyretics, 258. chemistry of, 255. Antipyrin, 251 , 255, 261, 373. Antisepsis, 32. intestinal, 57 , 58. of eye, 48. of mucous membranes, 44. Antiseptic solution, 45. Antiseptics, 18 , 58. and disinfectants, local, 32. chemical, 30. internal, 51. Antiseptol, 38. Apocynum, 276, 311. Apomorphin hydrochlorid, 226, 245. Appendicitis, 131, 323. Apples, ferrated extract of, 393. Aqua ammonia:, 291. amygdalae amar®, 373. anisi, 373. camphor®, 289. cinnamoni, 373. fceniculi, 373. hamamelidis, 162. hydrogenii dioxidi, 34. menthae piperitae, 133, 374. menthae viridis, 374. Arbutin, 316. Argenti nitras, 155 , 180, 367, 370. nitras fusus, 181. nitras mitigatus, 181. Aristol, 38. Aristolochia serpentaria, 12S. Aromatic elixir, 255, 374, 375. Aromatics, 123. Arnica montina, 162. Arseni iodidum, 92. trioxidum, 91, 181. Arsenic, 89 , 182. and zinc chlorid, 181. antidotes for, 82. official preparations of, 91. solutions of, 92. therapeutics of, 94. trioxid, 91 , 95, 181. Arsenous acid, 1S2. iodid, 92. Artemesia pauciflora, 355. Arteriosclerosis, 305. Asafetida, 134. Asagraaa officinalis. 201 , 302. Ascarides, 354 , 358. Ascaris lumbricoides, 356. Aspidium, 360, 361. Astringents, 138. 141, 146, 148. 152. Atropa belladonna, 196, 287. Atropin, 189, 196, 198, 248, 254. 285 , 298. indications for, 287. sulphate, 196, 209, 287 . Aurantii amari cortex, 127. Bacillus putrificus, 53. typhosus, 58 , 64. Bacteria, effect of bile on, 56. putrefactive, 59. Baking soda, 178. Balsam of copaiba, 369. of Peru, 37, 41 , 228 . of tolu, 227. Barberry, 123. Basham’s mixture, 81. Bateman’s pectoral drops, 393. Beebe’s serum, 104. Belladonna liniment, 198. ointment, 197. plaster, 197. Benzanilid, 257. Benzin, 206. Benzoic acid, 18, 41, 189 . Benzoinum, 228. Benzoyl ecgonin, 189. Berberis aquifolium, 123. Betanaphthol, 41, 61 . Bichlorid of mercury, 23, 43 . Bile, 328, 340 . Biliousness, 58 , 351. Biniodid of mercury, 43. Bioplasm, 349. Bismuth, insoluble salts of, 147, 148 . subcarbonate. 61. 148, 149 . subnitrate, 61, 148, 149. subgallate, 149. subsalicylate, 149. Bitter almond water, 373. Bitters, 125. Black mustard, 168. Blackberry root bark, 146. Blaud’s pills, 78 , 86. Blindness from wood alcohol, 161. Blisters, 173. Bloodletting, 307. Bloodroot, 224. Blue mass, 350. ointment, 44. stone, 154. vitriol. 24, 154 , 181. Borax, 47. Boric acid, 29, 37, 41. 45, 4S, 153, 370. as a gargle, 46. Bothriocephalus latus, 359. Brandy, 162, 293 . Bray era, 362. IXDEX. 399 Bromid group, 262. sodium and potassium, 260. Bromidia, 246 , 259, 394, 395. Bromids, 233 , 249. soluble, 375. Bromoform, 206. Bronchitis, 116 , 166. acute, 221. chronic, 235. Brown coloring, 381. mixture, 235. Burgundy pitch, plasters of, 166. Bums, 48. Butyl chloral hydrate, 261. Caffein, 252, 254, 285, 288, 311, 346. sodio-salieylate, 393. Calamus, 127. Calcii hypophosphis, 99. Calcium lactophosphate, 100. oxid, 22. Calendula officinalis, 162. Calomel, 55, 58, 10S, 113, 314, 336, 350, 357. Calumba, 122 , 126. Calx, 22. chlorinata, 25. Cambogia, 337. Camphor, 173, 288, 291, 318. liniment, 289. monobromated, 263. water, 48, 153. Camphorated soap liniment, 163. Cancer cures, 182. Cancerous growths, 182. Cannabis indica 245. Cantharidal collodion, 175. Cantharides, 174 , 317. cerate, 174. Cantharidin, 174. Capsicum, 166. fastigiatum, 166. Caramel, 381. Carbo ligni, 169. Carbolic acid, 19, 63, 202 , 259. acid as disinfectant, 26. C'armin, 380. Carminative, Dalby’s, 393. Carminatives, 130. Carvophyllus. 136. Cathartics, 320, 323, 350. anhvdrid group of, 333. drastic, 324. hydragogue, 325. saline, 341. saline non-irritant, 324. vegetable, 325. Cascara sagrada, 85, 332. Cassia fistula, 339. Castor fiber, 291. oil, 337. Castoria, 329. Caustics, 138, ISO. Caustic soda. 180. Cephaelis ipecacuanha. 221. Ceratum cantharidis, 174. resime, 165. Cerebral excitement, 312. Chalk mixthre, 145. Chamberlain’s colic, cholera, and diarrhea remedy, 135. Chapped hands, 186. Charcoal, 169. Charta sinapis, 168. Chenopodium anthelminticum, 356. Chimaphila, 316. Chirata, 123. Chloral, 209, 256 . and bromid compound, 394. camphorated, 167. hydrate, 246. Chloralamid, 259, 261 . Chloralose, 261. I Chloralum hydratum, 260. Chlor-anodyne, 395. Chloretone, 261. Chlorid of lime, 25. of zinc, 28. Chlorin, 25. Chlorodyne, 395. Chloroform, 36, 135, 163. 173, 205, 207, 209, 21S, 260, 364. and ether, action of, 211. anodyne, 394. liniment, 202. Chlorosis, 83, 95. Cholera vibrio, 56. Cholin, 95. Chrysophanic acid, 326. Cimicifuga, 125, 127 . Cinchona, 65, 125, 128 . Cinnamic acids, 18, 41. Cinnamon water, 373. Citrated caffein, 313. Citrate, iron and ammonium, 79. of magnesia, 345. of sodium and potassium, 317. Citric acid, 313. Citrullus eolocynthis, 334. Citrus vulgaris, 127. Claviceps purpurea, 295. Cleansing of hands, 33. Clinical thermometers, disin- fection of, 29. Cloves, 136. Coca, 192. Cocain, 30, 188 , 190, 208. habit, 190. hydrochlorid, 149, 192 . official preparations of, 192. Cochineal, 380. Cocoa butter, 185. Cod liver oil, 102. liver oil emulsion. 103. Codein, 232, 243, 244 . 400 PHARMACOPEIA AND PHYSICIAN. C'odein phosphate, 2322 , 244. sulphate, 232 , 244. Coffee, 142, 312. Cold bathing, 159. Cold cream, 185. water, laxative action of, 325. Colds, 190, 219, 300 , 318. Collodium cantharidatum, 174. Colocynthis, 334. Colon bacillus, 53 , 54. Colophony, 165. Coloring, suggestive, 380. Compound kino powder, 144. mixture of glyeyrrhiza, 235. powder of morphin, 318. solution of cresol, 26. solution of iodin, 115. solution of sodium borate, 394. syrup of hypophosphites, 100. syrup of sarsaparilla, 379. syrup of squill, 226, 231 . syrup of white pine, 224. tincture of cardamon, 377. tincture of lavender, 377. Confectio sennae, 330. Constipation, 324, 330, 343, 351. Convallaria, 276. Convolvulus seammonia, 334. Copaiba, 315, 369. Copper, 28. salts, 154. sulphate, 24, 28, 48, 181 . Copperas, 24 , 28. Corns, 180. Corrosive mercuric chlorid, 23, 33, 43 , 108, 353. Cotton seed oil, 185. Coughs, 219. Counter-irritants, 159 , 172. Council on Pharmacy and Chem- istry, 17, 250 , 387. Creolin, 26. Creosote, 32, 63, 65, 231 . Cresol, 26 , 29, 37, 39. compound solution of, 39. detergent action of, 40. Cresolin, 26. Crile’s pneumatic suit, 269. Croton chloral hydrate, 261. oil, 178, 179, 338 . tiglium, 179, 338 . Crotonoleic acid, 178. Cubeb, 315. Cucurbita pepo, 362. Cudbear, 381. Cumarin, 37. Cupri sulphas, 24, 154 , 181. Cusso, 362. Cystogen, 315. Dalby’s carminative, 393. Datura stramonium, 198. Delirium cordis, 272. Demulcents, 159. Depressants, circulatory, 297. Dermatol, 149. Dermatology', 41. Desiccated suprarenal glands, 158. Deshler’s salve, 165. Diabetes, 95. Diaphoresis, 317, 318. Diaphoretics, 290, 309, 31 7 . Diarrhea, 55, HO, 145, 146, 149, 325 , 338. Diet, 324. Diethylsulphonedimethvlmethane, 261. Digitalin, 272, 274 , 278, 279. German, 275. Digitalis, 266, 272, 277, 285, 294, 310 , 314. group, therapeutic action of, 276. purpurea, 274. tincture of, 278. vasoconstrictor effect of, 306. Digitin, 274. Digitonin, 275, 278. Digitoxin, 271 , 274, 278. Dionin, 245. Dioxymethyl anthraquinone, 326. Diphtheria, 35. Disinfectants and antiseptics, local, 27, 32 . chemical, 20, 21 . general, 18. Disinfection, 47. moisture needed in, 25. of bedrooms, 21. of body, 34. of cesspools, drains, urinals, cellars, etc., 23. of clothing and instruments, 33. of corpses, 23. of hands, 44. of wounds and ulcers, 34. sheet method of, 21. Disulphonmethvlethvlmethane, 262. Dithymol diodid, 38. Diuresis, 312, 314. Diuretics, 309, 313, 317, 318. Diuretin, 313. Dobell’s solution, 393, 394. Donovan’s solution, 93. Dormiol, 261. Dover’s powder, 222 , 31S. powder liquid, 243. Dropsy, 333. Dryopteris felix-mas, 361. marginalis, 361. Dyspepsia, 95. fermentative, 60. Ecballium elaterium, 335. INDEX. 401 Elaterin, 335. Elixir adjuvans, 372, 375 . aromaticum, 375. compound digestive, 395. ferri, quinin® et strychnin.'? phosphatum, 81. of laetopeptine, 395. of paregoric, 241. of terpin hydrate and codein sulphate, 229. Ellis’ medical formulary, 390. Emetics, 153. Emodin, 326. Emollients, 159, 183. Emplastrum belladonn®, 197. capsici, 166. Emulsion of castor oil, 103, 338. Emulsum asafoetid®, 134. chloroformi, 135. olei morrhu®, 103. Epinephrjn, 158, 190. Epispastics, 173. Epsom salts, 344. Ergot, 294. Ethacol, 232. Ether, 135, 205, 207, 2 18, 293, 364. administration of, 215. compound spirit of, 136. narcosis, 209. Ethereal oil, 136. Ethyl alcohol, 161. bromid, 206. carbamate, 258, 262. chlorid, 207, 210 , 213 , 217. morphin, 232. oxid, 293. Eucain, 30, 191 . Eugenia aromatica, 136. Euonymus, 335 , 337. atropurpureus, 335. Europhen, 37. Exalgin, 257. Exanthemata, 36. Exogonium purga, 333. Expectorants, 219. demulcent, 234. sedative, 221. Extract of belladonna leaves, 197. of eolocynth, compound, 334. of ergot, 295. of hematoxylon, 146. of hyoscyamus, 238, 246. of Indian cannabis, 238. of malt. 380. of stramonium, 19S. of witchhazel,' 162. Extractum aloes, 327. cannabis indie®, 246. digitalis, 275. gentian®, 121. glycyrrhiz® purum, 234. leptandr®, 335. opii, 241. quassi®, 122 , 356. rhamni purshian®, 332. Extrapharmacopeial substances, 382. Fel bovis, 340. Fellow’s syrup, 98. Fennel water, 373. Ferratin, 74. Ferri carbonas saceharatus, 78. et ammonii tartras, 79. et potassii tartras, 79. et quinin® citras, 80. et strychninae citras, 80. hydroxidum, 82. hypophosphas, 99. Ferric chlorid, 152, 154 . chlorid, tincture of, 86. citrate, 79 , 85, 86. hypophosphite, 99. salts, 157. subsulphate, 152. Ferrous carbonate, 78, 95. sulphate, 24, 28, 77, 85. sulphate, dried, 77 , 8b. Ferrum reductum, 79. Ferula, 134. Fever, malarial, 6S. Fig, 339. syrups, 329. Filicic acid, 360. Flaxseed, 169. Fluidextract of blackberry root bark, 146. of geranium, 146. of licorice root, 234. of red rose, 146. of rhus glabra, 146. Fluidextraetum aconiti, 200 , 299. apocyni, 276. aurantii amari, 127. belladonnas radicis, 197. berberis, 123. calami, 127. calumbas, 122. capsici, 166. chimaphil®, 317. chirat®, 123. cimieifug®, 128. cinehon®, 129. convallari®, 276. digitalis, 275. ergot®, 295. gentian®, 121. glycyrrhiz®, 234. granati, 361 . 402 PHARMACOPEIA AND PHYSICIAN . Fluidextractum hydrastis, 128. ipecacuanhas, 222. leptandrae, 335. nucis vomicae, 130. pilocarpi, 319. podophylli, 335. quassia, 122, 350. rhamni purshianae, 332. sanguinariae, 224. scilla, 231. scopola, 248. senega, 224. senna, 329. serpentaria, 128. spigelia, 356. staphisagria, 354. stramonii, 198. uva ursi, 316. veratri, 302. zingiberis, 131. Food preservatives, 30. Foot baths, mustard, 168. Formaldehyd. 24 , 30, 48, 315. solution, 29. Formic acid, 171. aldehyd, 21. Fowler’s solution, 93. Fracture of bones, 100. Fraenkel solution, 209. Frangula, 326. Fraxinus omus, 339. Friar’s balsam, 228. Gadus morrhua, 103. Gallic acid, 146. Gambir, 140, 143 . Gamboge, 337. Gangrene from phenol, 39. Garcinia hanburii, 337. Gargles, 46. Gastric juice, 56. ulcer, 147. Gastritis, chronic, 156. Gentian bitters, 125. and orange bitters, 125. Geranium, 146. German pharmacopeia, 179. Ginger, 131. Glandulae suprarenales sicca, 158. Glandulae thyroidae sicca, 118. Glonoin, 304. Glucose, 261. Glycerin, 24, 31, 42, 1S4. 1S6, 370. magmas, 171. Glycerite of boroglycerin, 47. of phenol, 203. of starch, 42. Glyeeritum acidi tannici, 143. amyli, 42. boroglycerini, 47. Glyeeritum ferri quinas et strych- nin* phosphatum, 81. phenolis, 203. Glycerol, 184. Glycerophosphoric acid, 100. Glyceryl trinitrate, 304, 305. Glycothymoline, 394.- Glyeyrrhiza, 234. compound mixture of, 225. compound powder of, 352, 331. Glyeerrhizin, 372 , 380. Glycyrrhizinum ammoniatum, 234. Godfrey’s cordial, 393. Goiter, hypoplastic follicular, 118. Golden yellow mixture, 381. Gonorrhea, 365 , 369, 370. Goulard’s extract, 151. Granatum, 361. Gray powder, 107 , 350, 351. Green soap, 33. Griffith’s pills, 78. Grindelia robusta, 178. Guaiacol, 64, 65, 231 . Guarana, 312. Hagenia abyssinica, 362. Hay fever, 188. fever remedies, 190. Headache, 168, 254. Heart, dilatation of, 277. disease of, 213. fatty degeneration of, 277. tonic, 264. Heat, 19, 169 , 269. Helmitol, 316. Hematin, 75. Hematinics, 71. Hematogen, 73. Hematoxylon, 146. Hemdglobin, 75. Hemorrhage, 294. Hemorrhoids, 195, 198. Hemp, Canadian, 2S1. Hernia, strangulated, 323. Heroin, 245, 3S6. Hexamethylenamin, 64, 315, 31S. History of Pharmacopeia, 7. Hive syrup, 231. Hoffman’s anodyne, 136, 293 . Homatropin hydroehlorid, 247. Hunyadi water, 344. Huxam’s tincture, 129. Hydrargyri chloridum corrosi- vum, 23, 43, 107 . chloridum mite, 10S, 350 . iodidum flavum, 107. iodidum rubrum, 43, 107 . Hydrargyrum, 106. cum creta, 107, 350. Hydrastinin, 157. Hydrastis, 128. INDEX. 403 Hydrated chloral, 237, 260, 307. Hydrazin, 256. Hydrobromic acid, 263. Hydrobromids, 263. Hydroehinon, 316. Hydrochloric acid, 56, 59. acid, dilute, 59. Hydrocyanic acid, 233. Hydrogen dioxid, 29, 34, 45, 47, 49, 59. 141. Hydroxybenzene, 38. Hydroxylamin, 256. Hyoscin, 248. Hyoscyaminas sulphas, 249. Hypnal, 256, 261. Hypodermic syringes, 29. Hypophosphites, 97. 101. Indian cannabis, 245. Indigestion, 131, 351. Infectious diseases, spread of. 33. Inflammation of stomach. 147. Infusion of digitalis, 275. of uva ursi, 316. Infusum digitalis, 275. sennas compositum, 330. Injections, intraspinous, for an- esthesia, 89, 193, 194. Insecticide, 44. Instrument disinfection, 33. sterilization, 27. Intestinal antiseptic, 56. Intestine, closure of, 323. spasmodic constriction of. 323. Introduction, 5. Iodids. 114 , 249. soluble, 375. Iodin, 37. 3S, 62, 171 . 172. compound solution of, 62, 115, 171. Iodoform, 35 , 36, 49. gauze. 37. Iodol, 37. Iodum, 62, 114. lodothyrin. 118. Ipecac, 221, 222. Iron, 71 , 76. acid albumin, 74. albuminate of, 71 , 76. and ammonium citrate, 87. and quinin citrate, 80. and strychnin citrate, 79. chlorid of, 154. compound mixture of. 78. indications for, 82. inorganic, 71 , 74, 84. organic, 73. peptonate of, 76. reduced, 79, 85. saccharated carbonate of, 78. salts, 154. scale salts of. 79 , 87. 375. Irritants, 159, 314 . Iso-punicin, 362. Jaborandi, 319. Jalap, 333, 336. powder, compound, 336. Jamaica quassia, 122, 356. Jateorhiza palmata, 122. Juniperus oxyeedrus, 41. Kairin, 258. Kamala, 360. Kataplasma kaolini, 170. Kino, 143, 144 . Kola, 312. Kopp’s Baby’s Friend, 135. Koso, 362. Kosotoxin, 360. Krameria, 143. Labarraque’s solution, 26. Lactic acid, 258. Laetophenin, 258. Lactucarium, 246. Lady Webster’s dinner pill, 328. Lanolin, 184. Laudanum, 241. of Sydenham, 241. Lauselcorner, 354. Laxatives. 331, 339 , 350, 393. Lead acetate, 153, 178. salts, official, 150. subacetate, solution of, 150. Lecethin, 95. Leptandra, 335, 337. Leuein, 53. Licorice root, 234. Lime, 22. liniment, 49. milk, 22. Linimentum belladonna, 198. calcis, 49. camphorae, 289. chloroformi, 163. saponis, 163. terebinthinae, 165. Linseed, 169. Linum, 169. Liquid carbolic acid, 38. opodeldoc, 163. petrolatum, 185. Liquified phenol, 38, 203. Liquor acidi arsenosi, 93. ammonii acetatis, 319. antisepticus, 29, 45. arseni et hvdrargyri iodidi, 93. eresolis compositus, 26, 39, 48. ferri chloridi, 154. ferri et ammonii acetatis, SI. ferri sulphatis, 77. formaldehvdi, 21. hydrargyri nitratis, 183. iodi compositus, 62, 115, 171. magnesii citratis, 345. plumbi subacetatis, 151. 404 PHARMACOPEIA AND PHYSICIAN. Liquor potassi arsenitis, - 93. potassii citratis, 318. sodae chlorinatse, 26. sodii arsenatis, 93. sodii phosphatis compositus, 347. zinc et alumini compositus, 26. zinc et ferri compositus, 26. Lithii carbonas, 348. citras effervescens, 348. Lithium salicylate, 348. Loganiaceae, 283. Loomis diarrhea mixture, 393. Loretin, 37, 38. Losophan, 37, 38. Lugol’s solution. 62, 171. Lumbago, 198. Lunar caustic, 180. Lymphosarcoma, 95. Lysol, 26. McMunn’s elixir of opium, 242. Magnesii carbonas, 344. oxidum, 344. Magnesium sulphate, 208 , 330. sulphate, effervescent, 343. Male fern, 359. Mandrake root, 335. Manganese, 87 , 88. dioxid, precipitated, 89. hypophosphite, 99. preparations, peptonized, 88. Mangani dioxidum praecipita- tum, 89. hypophosphis, 99. sulphas, 89. Manna, 330, 339, 340. Massa ferri carbonatis, 78. hydrargyri, 107 , 350. Matico, 315. May apples, 335. Medicated waters, 373. Menstruation, 253. Mentha piperita, 132 , 167. viridis, 133. Menthol, 167 , 173. Mercurial ointment, 353. Mercurials, 43 , 105, • 106, 10S. Mercuric ehlorid, 23, 27, 33, 43 , 44, 48, 10S, 1S2, 353. iodid, 111. nitrate, 183. oxid, red, 44 , 353. salicylate, 113. Mercurous ehlorid, mild, 5S, 108 , 113, 350. iodid, 111. iodid, yellow, 107. Mercury, 106. hypodermic injection of, 113. in pregnancy. 111. with chalk, 107 , 350. Methemoglobin, 253, 303. Methyl aeetanilid, 257. alcohol, 161. punicin, 362. salicylate, 173. Mineral acids, 27. Mints, official, 132. Mistura cretae, 145. ferri composita, 78. sodae et menthae, 133. Mitral stenosis, 277. Mixture for general anesthesia, 207. Monsel’s solution, 77. Morphin, 195, 232, 240, 239, 243, 260, 270, 282, 285. habit, 347. sulphate, 373. Morphinae acetas, 243. Morphinae hydrochloridum, 244. Morphinae sulphas, 244. Moschus moschiferus, 290. Mouth wash, 35. M. S. mixture, 207. Mucilage of acacia, 234, 379 . of tragacantli, 1S4, 379. Mucous membrane antisepsis, 44. membranes, local treatment of, 151. Muriatic acid, 59, Muscarin, 28S. Musk, 290. Mustard, 137, 174 . paper, 168. poultice, 169. Mydriaties, 247. Myocardium, improved nutri- tion of the. 267. Myxedema, 118. Naphthalen, 41, 56, 60 , 364. Naphthol, 41, 61 . Nasal passage antisepsis. 46. National Formulary', 382. Nephritis, 174, 310 , 314. Nerves in teeth, destruction of, 182. Neuralgia, 167, 198, 201. New remedies, dangers from, 3S4. Xiemeyer’s pills, 310. Nitrates, 302. Nitric acid, 182. Nitrites, 303, 305 , 307. Nitroglycerin, 304. Nitrous oxid, 204. Norwood’s tincture of veratrum, 301. Nosophen, 37. Nuclein, 95. Nutmeg, 137. Nux vomica, 86, 130 , 283. Obesity, 104, 118. Obstetricians, 213. INDEX. 405 Oil of almonds, expressed, 185, 337. of American worm seed, 358. of cade, 41. camphorated, 289. carron, 49. castor, 337. of chenopodium, 356, 358. of cinnamon, 137. of cloves, 164. of copaiba, 164, 369. cotton seed, 185, 337. croton, 337. of cubeb, 369. ethereal, 136. of juniper, 315. of juniper tar, 41. of mustard, volatile, 164. olive, 185, 337. of pennyroyal, 164. petroleum, 104. . purgative, 337. of sandalwood, 164, 368. of santal, 368. of savin, 165. of theobroma, 185. of thymus vulgaris, 40. of turpentine, 165, 315. of turpentine, rectified, 364. volatile, 45, 123, 164, 315. of wintergreen, 69. Ointment of ammoniated mer- cury, 183. carbolic, 354. of mercuric nitrate, 1S3. of mercury, 44. of phenol, 203. of red mercuric oxid, 44. of red precipitate, 44. of rose water, 185. stramonium, 198. of sulphur, 42. of tar, 41. Oleate of atropin, 197. of eocain, 192. of veratrin, 201. Oleoresin, 359. of aspidium, 361, 364. Oleoresina capsici, 167. cubebae, 369. zingiberis, 132. Oleum amygdalae expressum, 185. betulae, 69. cadinum, 41. caryophylli, 136. chenopodii, 356. copaibae, 369. gaultherias, 69. gossypii seminis, 185. jecoris aselli, 103. menthae piperitae, 132. morrhuae, 103. Oleum olivae, 185. ricini, 337. rosmarini, 165. sabinae, 165. santali, 368. sinapis volatile, 168. trebinthinae, 165. theobromatis, 185. tiglii, 179, 33S. vitroli dulce, 293. Opii pulvis, 240. Opium, 146, 195, 238, 339, 270, 323. deodoratum, 240. deodorized tincture of, 242. McMunn’s elixir of, 242. official preparations of, 239. poisoning, 288. Orange and gentian bitters, 125. peel, bitter, 127. Osteomalacia, 100. Ourouparia gambir, 144.' Ovis aries, iS4. Oxyanthraquinone, 326. Oxyuris yermicularis, 358. Packer’s tar soap, 176. Para-amido-phenol, 257. Paraldehyd, 259, 261. Paralysis, local intestinal, 323. Parasitic fungi, 42,__ Parasiticides, 44, 353. Paregoric, 241. Parenchymatous nephritis, chronic, 351. Patent medicines for coughs, 219. Peacock’s bromids, 263. Pearls of amyl nitrite, 307. Pearson’s solution, 93. Pectoral species, 393. Pediculi, 44. Pediculus pubis, 353. Pelletierin, 359, 360. tannate, 361. Penicillium brevicaule, 89. Pepo, 362. Pepper, 137. Peppermint, 132, 133. water, 374. Peptomangan-Gude, 88. Peptonate of iron, 76. Peptonized manganese prepara- tions, 88. Periostitis, 116. Peristalsis, 55, 59, 322. Peritonitis, 131, 323. Peru balsam, 37. Petrolatum, 184. album, 185. liquidum, 185. Petroleum ether, 206. oils, 104. saponated, 172. Pharmacopeia, 5. 406 PHARMACOPEIA AND PHYSICIAN. Phenacetin, 251 , 255, 257. Phenalgin, 250. Phenetidin, 257. Phenocoll, 258. Phenol, 19, 26, 29, 32, 38, 63, 189, 202, 257, 359, 370. Phenolphthalein, 341. Phenolsulphonic acid, 63. Phenylaeetamid, 250, 257. Phenyl-dimethyl-pyrazolon, 251. Phenylhydrazin, 256. Phenyl salicylate, 64 , 69. Phosgene, 208. Phosphates, 97. of iron, quinin and strychnin, 81. Phosphoric acid, 99. Phosphorus, 95, 96, 98, 101. and its salts, therapeutics of, 100 . Phthisis, 97. Picrasma excelsa, 122, 356. Picrol, 38. Pills of aloes and iron, 77 , 85, 328. of aloes and mastic, 328. of aloes and mvrrh, 328. Blaud’s, 78 , 86. compound cathartic, 336. Connecticut, 390. of ferrous carbonate and potassium sulphate, 78 , 86. Francis’, 337. Griffith’s, 78 , 86. Lady Webster’s dinner, 32S. of lead and opium, 147. Lee’s, 390. of rhubarb, compound, 328. triplex, 337. Vallet’s, 78. vegetable cathartic, 328, 334. Pilocarpin, 288, 318. nitrate, 319. Pilocarpus, 318, 319. aloes et ferri, 77. asafostid®, 134. cathartic® composite, 334. ferri carbonatis, 78. laxative composite, 327. opii, 241. phosphori, 98. Pink root, 356 , 35S. Pinus, 41, 165. palustris, 165. Pipsissewa, 316. Pix liquida, 41. Plasters, resin, 166. rubefacient, 166. rlumbi acetatis, 150. Podophyllum, 335 , 336. Poison oak, 178. Polygala senega, 224. Pomegranate, 361 . Pomegranate root bark, 363. Potassa, 180. Potassii chloras, 45. et sodii tartras, 345. hypophosphas, 99. iodidum, 116. permanganas, 49 , 89, 367. Potassium and antimony tar- trate, 179 , 226. bicarbonate, 133. bitartrate, 336. bromid, 237, 238, 262 , 312. chlorate, 45. citrate, 318 , 373. hydroxid, 180. hypophosphite, 99. iodid, 106, 111, 263. permanganate, 27 , 49, 59. sulphate, 152. tartrate, 225. Poultices, 169. Powder, antiseptic astringent, 48. compound of glyeyrrhiza, 331. 352. Dover’s, 222 , 318. of ipecac, 318. of ipecac and opium, 222. of opium, 318. Powdered blue mass, 107. Precipitate, red, 353. Pregnancy, use of mercurials in, 351. Preservatives, 31. Probilin, 341. Protozoon, 6S. Prune, 339. Pseudo-punicin, 362. Pterocarpus marsupium, 144. Pulvis acetanilidi compositus, 250. glyeyrrhiz® compositus, 235 , 330. iodoformi compositus, 37. ipecacuanhas et opii, 222 , 243. jalap® compositus, 333. morphin® compositus, 318. Pumpkin seed, 360, 364. Punica granatum, 361, 362. Punicin, 362. Purgatives, 324. irritant, 55. Pustulants, 178. Pyoktannin, 4S. Pyrogallic acid, 40. Pyrogallol, 40. Quassia, 122, 356. Quassia amara, 122, 356 . Quinin, 51, 65, 255 . Quinin® bisulphas, 66. hydrobromidum, 66. hydrochloridum, 66. INDEX. 407 Quininas salicylas, 66. sulphas, 66. Quinolin, 38, 255. Red coloring, 381. iodid, 112. mercuric iodid, 43, 107 . wine, 378. Reduced iron, 85. Remedies, new, 383. Resin of jalap, 333, 336. of seammony, 335. plasters, 166. Resina, 165. podophylli, 335. Resorcin, 40, 259. Resorcinol, 40, 259. Rhamnus purshiana, 332. Rheum, 331. Rheumagon, 347. Rheumatism, 201. chronic, 117. Rhubarb, 326, 331. official preparations of, 331. Rhus glabra, 146. poisoning, 177. Ricinus communis, 337. Rickets, 100, 104. Rochelle salts, 345. Rose water, 187. Rosin, 165. Rosmarinus officinalis, 165. Rubefacient plasters, 166. Rubefacients, 160. Rubus, 146. Rumex, 326. Sacred bark, 332. Salacetin, 250. Sal alembroth, 43. ammoniac, 226. hepatica, 349. Salicin, 69. Salicylates in rheumatism, 68. Salicylic acid, 30, 40 , 41, 257, 259. Saline cathartics, 341. purgatives, 321, 325. Salipyrin, 257. Sal-lithin, 349. Salol, 64, 328. Salophen, 258. Salt, common, 47. solution, physiologie, 269. Salts, purgative, 344. Rochelle, 345. Sanguinaria, 224. Sanguinarin, 224. Santalol, 369. Santalum album, 368. Santonin, 355, 357. Sarsaparilla, compound svrup of, 330. Scalds, 48. Seammony, 334, 336. Schleich’s infiltration method, 195. Scilla, 230. Scoparin, 314. Scoparius, 314. Scopola, 248. carniolica, 248. Scopolamin-morphin solution, 208. Scopolamine hvdrobromidum, 248. Semen staphidis pedicularis, 354. Senega, 224. Senna, 326, 329, 358. Serpentaria, 125, 12S. Serum of Beebe, 104. Shock, 268, 280, 284, 287, 289, 294. Silver, 155. iodid, 368. nitrate, 48, 155, 180, 370. nitrate, mitigated, 181. Sinapis alba, 168. nigra, 16S. Slippery elm, 169. Smelling salts, 292. Soap liniment, 163. liniment, camphorated, 163. Packer’s tar, 176. Soda, 21. Sodii arsenas, 92. arsenas exsiccatus, 92. hypophosphis, 99. nitris, 304. Sodium acetate, 313. benzoate, 312, 373. bicarbonate, 46, 133, 178. borate, 47, 48. bromid, 255. chlorid, 27, 47. 269. hyposulphite, 42. iodid, 347. nitrate, 304. phenolsulphonate, 47 , 63. phosphate, 346. salicylate, 68, 312, 313, 373. santoninate, 355. sulphocarbolate, 47 , 63. thiosulphate, 42 , 172. Solution, alkaline antiseptic, 45. of arsenous acid, 93. of chlorinated soda, 26. Donovan’s, 93. of ferric chlorid, 77. of formaldehyd, 21. Fowler’s, 93. Fraenkel’s, 209. of hydrogen dioxid, 34. of iodin, compound, 62. of iron and ammonium acetate, 81. Lugol’s, 62. 408 1'llARMACOPEIA AND PHYSICIAN. Solution, Monsel’s, 77. Pearson’s, 93. of potassium arsenite, 93. of potassium citrate, 318. of sodium arsenate, 93. Soporifics, 237. Sore throat, 35. Sozoiodol, 38. Spanish flies, 174. Spartein, 314. Spartinae sulphas, 314. Spearmint, 133. water, 374. Spigelia, 356, 358. marilandica, 356. Spirit of ammonia, 292. of anise, 375. of bitter almonds, 375. of cinnamon, 376. distilled, 292. of ether, 295. of formic acid, 393. of gaultheria, 376. of glyceryl trinitrate, 306. of minderevus, 319. of niter, sweet. 319. of nitroglycerin, 306. of nitrous ether, 306. of peppermint, 133, 376. of spearmint, 376. Spiritus aetheris, 136, 293 . aetheris compositus, 136, 293 . aetheris nitrosi, 319. ammoniae aromaticus, 292. amygdalae amara, 375. camphors, 163, 289 . chloroformi, 135. frumenti, 162, 293 . gaultheriae, 163, 376 . glonoini, 304. glycerylis nitratis, 304. menthae piperitae, 132 , 376. menthae viridis, 376. villi gallici, 162, 293 . Splanchnic area, 2S6. Squibb’ s rhubarb mixture, 393. Squill, 230 , 310, 314. Staphisagria, 353. Steam, moist, 21. Sterilization of hypodermic so- lutions, 29. of surgical instruments, 27. Stimulant, cardiac, 285, 311 . circulatory, 264 , 276. respiratory, 284. Stimulation, mechanism of, 265. of constrictor mechanism, 269. Stomachics, 70. 11S. Stovain, 30, 191 . Stramonium ointment, 19S. Strontii iodidum, 116. salieylas, 69. Strontium salts, 263. Strophanthin, 272, 275, 279 . as local anesthetic, 311. Strophanthus, 272, 275 , 311. kombe, 275. seed, 280. Strychnin, 281 , 288, 294. vasoconstrictor effect of, 306. nitrate, 284. sulphate, 283. Strychnos nux vomica, 130. Styptics, 157. Sugar, 31. of lead, 151. of milk, 314. Sulphonal, 259, 261 . Sulphonethylmethane, 259, 261 . Sulphonmethane, 259, 261 . Sulphur lotum, 42, 351 . ointment, 42. precipitatum, 42 , 351. sublimatum, 24 , 42, 351. washed, 42. Sulphuric ether, 135 , 293. Sulphurous oxid, 24. Sumbul root, 291. Sunburn, 186. Sunlight and heat, 19. Supersaturated air, 21. Suppositories, 198. Suprarenal gland, desiccated, 157, 158 . Suprarenin, 158. Surgical dressings, 35. Sweet flag, 127. Swertia chirayita. 123. Synthetics, introduction of, 15. Syphilis, 109. tertiary, 116. Svrup of blackberry root bark, 146. of citric acid, 378. Fellow’s, 98. of hydriodic acid, 115. of liypophosphites. compound, 100 . of iodid of iron, 116. of ipecac, 222. of orange, 378. of red rose, 146. of senna, 357. of squill, 230. of squill, compound, 226. of tar, 229 , 233. of tolu, 227 , 22S. 37S. of white pine, 225. of wild cherry, 378. Syrupus acaciae, 234. 379 . calcii lactophosphatis, 100. ferri, quininae et strychinnae phosphatum, 81. lactucarii, 247. picis liquids, 229. INDEX. 409 Syrupus pruni virgihianae, 378. "sarsaparillae compositus, 379. senegae, 224. Tablets, soda mint, 133. Taenia inermis, 360. saginata, 359. serrata, 360. solium, 359. Talcum, 41. Tamar-Indien, 330. Tamarindus, 339,. Tannate ot pelletierin, 362. Tannic acid, 141, 370. Tannin, 139, 156. 363. Tapeworm, 361, 363. Tar, 32, 41. ointment, 41. soap, 353. Tartar emetic, 178, 179, 226. Tea, 142, 312, 313. Teeth, carious, 195. Teniafuges, 354, 359, 362. official substances used as, 361. Tenicides, 354. Terebene, 230. Terebinthina, 165. Terpin hydrate, 229. Tetra-iodopvrrol, 37. Thallin, 259. Thea sinesis, 313. Thebaica, 240. Theobromin, 285, 312. sodium, 313. Thermometers, clinical, disin- fection of, 29. Thermo-cauterv, ISO. Thymol, 40, 63, 65, 364, 370. iodid, 38, 40. Thymus vulgaris, oil of, 40. Thyroid gland, 104, 11S. disease, 104. Tinctura aconiti, 200, 299 . amieae, 162. asafoetidae, 134. aurantii amari, 127. aurantii dulcis, 376. benzoini composita, 228. calendula?, 162. calumbae, 122. cannabis indicae, 246. cantharidis, 175. eapsici, 167. cardamomi composita, 129 , 377, 381. eimieifugae, 128. cinchona, 129. cinehonae composita, 129. digitalis, 275. ferri chloridi, 77, 154. gambir composita, 144, 149. gentianae composita, 121. hydrastis, 128. Tinctura iodi, 62 , 115, 171. ipeeacuanhae et opii, 243. kino, 144, 147, 149. lactucarii, 246. lavandulae composita, 377. moschi, 290. nucis vomicae, 130, 374. opii, 241. opii camphorata, 241. opii deodorati, 242. quassiae, 123 , 356. scillae, 231. serpentariae, 128. strophanthi, 275. tolutana, 227. vanillae, 377. veratri, 302. zingiberis, 131. Tincture of aloes, 32S, 329. of aloes and myrrh, 32S. of calumba, 374. of cardamon, 377. of cudbear, 381. of ferric chlorid, ethereal, 393. Huxam’s, 129. of krarneria, 145, 147, 149. of larkspur, 353. of soap, camphorated, 163. of stavesaere, 353. of sweet orange peel, 372, 376 . of thebaica, 240. Toluifera balsamum, 227. Tonics, general, 70. Toxicodendrol, 177. Toxicology of. strychnin, 283. Tri-iodomethane. 35. Trional, 259, 261 . Trioxymetholanthraquinone. 326. Trochisei acidi tanniei, 143. ammonii chloridi, 227. gambir, 144. glycyrrhizae et opii, 234 , 243. Tubercle bacillus, 56. Tuberculosis, 95, 97, 101, 103, 351. Turlington’s balsam, 22S, 393. Turpentine, 173. Typhoid bacilli, 20, 2S, os. fever, 62. Tvrosin, 53. Ulcerations of throat, 152. Ulcers, 49, 149. Ulmus, 169. fulva, 169. Unguentum aquae rosae, 185. belladonnas, 197. hydrargyri, 44. hydrargvri ammoniati, 183. hydrargyri nitratis, 183. hydrargyri oxidi rubri, 44. iodi, 171. 410 PHARMACOPEIA AND PHYSICIAN. Unguentum phenolis, 203. picis liquid*, 41. stramonii, 198. sulphuris, 42. veratrin*, 201. United States Pharmacopeia, 5. Urea, 314. Urethane, 258, 2G2 Urginea maritima, 230. Uric acid solvent, 348. Uriform, 316. Urine discoloration from phenol, 39. Urotropin, 315. Uva ursi. 316. Vallet’s mass, 78. pills, 78. Vasoconstriction, 280, 311, 313. Vasoconstrictors, 156. Vasomotor spasm, 305. Vegetable calomel, 336. infusions, 318. Vehicles, substances used as, 371. Veratrin, 199, 201, 302. ointment, 201. Veratrum, 301. viride, 301. Vermicides, 354. Vermifuges, 354. Vesication, 173, 174. Vesicants, 173. Vinegar of opium, 241. of squill, 231. Vinum album, 377. antimonii, 225. ergot*, 295. ferri, 80. ferri amarum, 80. ipeeacuanh*, 222. opii, 241. rubrum, 378. Vioform, 37. Virginia snakeroot, 128. Vitis vinifera, 377, 378. Volatile oils, 31, 45. Warts, 180, 183. Whisky, 162. White mustard, 168. Wine of ipecac, 222. of iron, bitter, 87. white, 377. Winslow’s Soothing Syrup, Mrs. 135. Wintergreen, 376. Witchhazel extract, 162. Yellow mercurous iodid, 107. Zinc acetate, 154, 369. and arsenic chlorid, 181. chlorid, 48, 182, 370. oxid, 41, 154. phenolsulphonate, 63, 152 153, 370. salts, use of, 152. sulphate, 152, 369. sulphocarbolate, 153. Zingiber, 131. -