Elements of active-principle therapeutics

Front matter

Book. -F*/£

COPYRIGHT DEPOSm

Elements

Index

PAGE

The Development of Active-Principle Therapeutics . . 1

The Fundamental Laws of Active-Principle Therapeutics 15

The Minor Peculiarities of Active-Principle Therapeutics 33

The Materia Medica of Active-Principle Therapeutics 49

The Active-Principle Treatment of Pneumonia 65

The Treatment of Typhoid Fever 79

The Treatment of Acute Infections 97

The Management of Chronic Maladies 113

Preface

Nothing has ever been written — or at least nothing has ever come to my notice — which has seemed to me equal, as an introduction to the use of the active principles according to the method of the immortal Burggreave, to the first edition of Dr. Shaller's "Guide to Alkaloidal (Dosimetric) Medication." Especially did this work meet the wants of the times in which it was written, when the method described was a new one, and the physicians into whose hands the work might fall, needed to be enticed into the use of the new forms and ways by the skill of a master not only of medicine but of language.

But now that the dosimetric method has been modified, naturalized, and re-named, as a result of its introduction into and popularization in America by Dr. Abbott and his ever-increasing band of fellow workers, it seems desirable to have a re-statement of the old truths in the new forms. It is this which is attempted in the little work which is here presented — which is, indeed, but a primer of its subject, and aims only to state the fundamentals of active-principle therapy as clearly, as definitely, and as briefly, as lies in the power of its author.

Milford, iMass., March, 1916.

Elements of Active-Principle Therapeutics

CHAPTER I The Development of Active-Principle Therapeutics

\\T HEN I was a student in Dartmouth Medical ^ School, one of the professors told us a little story one afternoon, to while away an otherwise dull hour, which made so deep an impression on my mind that I have never forgotten it.

It was the story of a young man who had been suffering for a long time from some obscure disease and was steadily growing worse, while the attending physician gave little hope of his recovery. Finally, as a last resort, and at the request of the patient's father, a consultation was held, six of the ablest physicians in the vicinity being summoned to examine the sick man and consider what could be done for him. The doctors met, and each one made a thorough study of the patient and his symptoms, after which they retired to a private room for consultation. Meanwhile the anxious father, determined to know the opinion of the consultants at first hand, and not as it might be doctored up and given out in the interests of the attending physician, had secreted himself in a closet in the room where the physicians were to meet and listened intently to the discussion which took place.

One by one, beginning with the eldest and coming down to the youngest, as is duly provided by the code of ethics, these wise and scientific men delivered themselves each of his own opinion as to the diagnosis and pathology of this baffling case and each offered the best explanation he could present of the obscure and unusual symptoms from which the patient was suffering.

The Thing of Most Interest— The Curo.

Finally, when all the older men had spoken, it came the turn of the youngest and last of the six. ' ' Gentlemen, ' ' he began, "we have spent all our time thus far in considering the nature of the disease from which this man is suffering. The thing which interests me most is, what will cure him."

In the closet the listening father in his heart applauded and quickly registered the vow, "This is the doctor that shall treat my son."

So it is that men seek a physician to be cured of their diseases or be relieved of their pains; and he is a poor doctor, from their standpoint at least, who can not grant them the one boon or the other. To the physician the diagnosis is important and the pathology is essential; but to the poor victim and his friends the cure is everything. To the men and women who- employ us, who pay our bills and furnish us a living, we are simply doctors, and not scientific men ; curers, and not preventers of disease. From their point of view, the doctor who, when called to attend a sick man, tells him at the outset that his disease is self -limited and must run its course, that it can not be aborted, cut short or modified in any way by medical treatment, is not worthy of the name of physician and has no excuse for pretending to treat the sick.

And, frankly, when you come to think about it, how would you like that kind of a doctor to treat you when you are sick ? When that time comes, you will be likely to feel that the real business of a doctor is to cure you ; and if he does not know how, then his business is to find out how. You will be apt to realize then that the diagnosis and pathology of disease are merely preliminaries to the all-important business of treating, and, if possible, curing the sick person.

My good friend, your dean, suggested to me some months ago that he would like to have me give a few talks on some practical subject to the students of this college. When in response I proposed to talk to you about active-principle medication — than which I know of no more practical subject in medicine — he expressed a fear lest I might find it difficult to interest you in such a subject.

I confess that I was somewhat surprised at this reply ; for I am unable to understand how it can be possible that you, who have undertaken to fit yourselves to practice medicine, could fail to take a lively interest in the most important part of the curriculum, the treatment of disease. Surely, this can not be true — it is unthinkable. There are only two explanations which occur to me, .and the first is that my friend himself is not convinced of the practicability and superiority of the methods which I shall advocate ; but from my long acquaintance with him I can not believe that such is the case. There remains only the alternative that the Doctor fears I may not be able to put the matter in such a way as to make it clear, and plain, and attractive to you. Well, that is up to me — and to you, to decide.

Active-Principle Medication Not a "New System"

Active-principle medication (which is also known as dosimetry, alkalometry, alkaloidal medication, active-principle therapeutics, and by various other names) is not, and does not claim to be a new system of medicine, but only a new method of employing drugs; and I believe, and shall endeavor to convince you, that it is at once the most potent, the safest, the most convenient, and in every way the most satisfactory — both to patient and physician — of all known ways of using drugs for the cure of the sick.

It is. in no sense a school or a sect, and must not be so understood.

Active-principle medication stands for therapeutic optimism, as opposed to the prevalent therapeutic nihilism of the day. The active-principle physician is a man who believes he can do things. He believes that remedial agents, when properly administered, positively do exert a favorable influence upon the course and termination of disease-processes. And not only does he hold this as an abstract truth, but he confidently affirms, as to a large class of cases, that he has found the drugs that will do the work, and has learned how and when to administer them so as to obtain the desired result; while, as to the remainder, he is searching diligently for the means required, and confidently looks, day by day, for their discovery.

There has been great progress in all departments of medicine during the last quarter of a. century, and not the least in the department of therapeutics. The change has included the forms of the medicines used, the methods in which they are administered, and the indications for which they are employed.

When I began to visit patients with my preceptor, he used to carry a big black trunk filled with nauseous pills and powders and liquid abominations. Today I can carry more kinds of drugs (and do vastly better work for my patients) in a pocket-case of 2-dram vials filled with clean, neat-looking granules or tablets.

My preceptor gave saltpeter and "spirits of niter" to lower the temperature in typhoid fever, with powdered opium to lock up the secretions and relieve the pain, and brandy or whisky to start up the flagging pulse. I, today, go about it in a very different way.

He did not care to begin the treatment until the symptoms were well marked and the diagnosis evident. I want to see my patient at the earliest possible moment, before I or anybody else can tell what is the nature of the fever from which he is suffering.

His endeavor was to conduct the sick man safely through the various phases of the dreaded disease, and save his life by heroic measures, at the last, if necessary. My aim is to save him serious illness, if possible — and, if I can do it without permitting the development of symptoms enough to warrant a definite diagnosis, I am so much the better pleased ; and so is the patient.

A Mighty Progress: The Active-Principle Materia Medica

Now, I do not mean to intimate that all the progress in therapeutics has been in the direction of the active principles, for that would be absurd. We have the synthetics, and the animal extracts, and the serums and antitoxins, electrotherapeutics, spondylotherapy, and other forms of physical therapy and many things equally important; and no one treats diseases as they were treated forty years ago. But it is my desire to interest you in the use of the active principles after the manner of Burggraeve and Abbott, and their followers.

It was one of Boston's honored pharmacists, Mr. F. A. Davidson, president of the Theodore Metcalf Company, who, on one occasion, said in the local medical society, of which I am a member, that the alkaloidal granule represented the highest development of the art of the pharmacist. And it was another of the most prominent pharmacists of the country, Mr. J. K. Lilly, of Indianapolis, president of the firm of Eli Lilly & Co., who in, a recent article in TJie Pharmaceutical Era upon the development of American pharmacy, after describing some of the improvements which have already been made and still remain to be made in pharmacy and therapeutics, adds:

"We further predict that even more radical changes will occur in the next quarter century ; that all the progress of the one just closing will be as child's play compared to that which will be experienced between 1912 and 1937. Crude drugs will gradually disappear, to be replaced by active principles, synthetic products, and biologies. The practice of injecting intramuscularly and intravenously will increase. Punishing the stomach with large, frequent, and nauseous doses is bound to give way where possible to more refined and direct methods. Medicine will become less and less empirical, and more and more rigid demands will be made upon the manufacturer. We are profoundly convinced that these demands will be fully met. ' '

The Development of the New System

Let me now sketch for you in brief outline the development of this new system, which can be traced in three successive steps, the first of which made the system possible, the second made it an accomplished fact, while the third made it an indispensable necessity to every progressive physician.

The initial step consisted in the discovery of the alkaloids and other active principles of medicinal plants, thereby providing the necessary material.

The first of the alkaloids to be brought to the knowledge of the medical profession was morphine, which was isolated and described by the apothecary Sertuerner, in the year 1816. Within the next sixteen years, strychnine, brucine, quinine, eiiichoiiiiie, narcotine, codeine, vera.trine, coniine (or cicutine), atropine, nicotine, aconitine, and hyoscyamine were discovered by different chemists, so that by the end of the first third of the nineteenth century no less than thirteen alkaloids were known and prescribed by physicians. Since then numerous additions have been made to the list of active principles, which includes not only the alkaloids proper, but many rosins and gluoosidos, besides some misccllaneons principles, and concentrations sufficiently potent to allow them to be classed either as active principles or with them.

Many of the latter class of remedies were up to a recent date manufactured by B. Keith & Co:, of New York, and by Lloyd Brothers, of Cincinnati. They were for a time enthusiastically advocated and largely employed by the eclectics ; but most of these so-called resinoids were later discarded by them, as a, school, in favor of what are called the "specific medicines" that were first introduced by Dr. Scudder, and afterward manufactured by the Lloyds and by Merrell. At present, along with these active vegetable derivatives — not, indeed, similar to them in derivation, but similar in use — are included a considerable number of the more potent chemical synthetic and inorganic substances, which are largely used by the active-principle therapists.

The Principle of Dosimetry: Minute, Frequent Dosage

The second step in the development of active-principle therapeutics consisted in the establishment of certain general principles governing the use of the active principles as to methods, indications, and dosage, for the purpose of accomplishing certain definite therapeutic results. This revolutionary step was brought about by the master-mind of Burggraeve, of Belgium, who conceived and elaborated the method which he named dosimetry.

Dr. Burggraeve had seen the defects of the old systems ,of therapeutics, in which the natural drugs were the sole medicinal resources of the doctor. These were administered mostly in their crude form or in the shape of voluminous mixtures, and were inconvenient to carry, unpleasant to take, very uncertain as to action, and decidedly unsatisfactory in their results. From such a combination eventually, and inevitably, there came into being, on the one hand bald therapeutic nihilism and, on the other hand, blind faith in the various forms of suggestion.

Adolph Burggraeve was born in Ghent, Belgium, in the year 1806. He died in 1902, after nearly a century of life spent in his chosen profession, the later years of his active life having been devoted to the development of the system of therapeutics, which is his masterpiece. He became professor of anatomy, and later of clinical surgery, in the University of Ghent ; also he was a member of the Royal Academy of Brussels. It was at the latter institution that he conceived and elaborated the system of dosimetric medication — an enduring foundation upon which his fame will ever rest.

The Principles of Dosimetry, According to Burggraeve

As stated by Burggraeve, dosimetric medicine rests essentially upon its power to jugidate those fevers in ivMcJi all acute maladies have their commencement. Its great end is to prevent anatomo-pathologic (this is Burggraeve 's own wording) lesions, for these once established are above the resources of art.

The study of morbid causes he declares to be indispensable, since without it medicine is little more than empirical. The dosimetric medicaments are simple,, never composite or amalgamated. The "dominant" treatment, as it is known in dosimetric practice, consists in attacking the morbid cause. The "variant" treatment is applied to those symptoms through which the diseased organism makes known its sufferings.

To acute maladies, dosimetry opposes a sharp and active treatment, while chronic maladies are combated by more deliberate methods of treatment, That is to say, in acute maladies the treatment must proceed as rapidly as the disease, in order to prevent organic disturbances;

but in chronic maladies the treatment should proceed slowly, in proportion to the lengthened duration of the disease.

The medicaments most commonly administered are the single, proximate principles, such as the alkaloids, which are given in divided doses, usually in the form of soluble granules.

These are, in substance, the words of Burggraeve himself and may be taken to represent accurately the spirit of dosimetric medicine as understood by its founder. It is worthy of note that he gives the place of first importance to the object to be accomplished, and the second only to the medicaments to be prescribed.

Although Burggraeve was able to show remarkable results in the treatment of disease by his new method, yet he did not succeed in securing its adoption to any considerable extent, until after he had interested Chantaud, a noted pharmacist of Paris, in his undertaking, and formed an alliance with him, according to which the latter thereafter devoted his great skill to the manufacture, of the highest grade of alkaloidal granules that had ever been produced, and in this way became the practical coworker with Burggraeve in building up his new therapy. From this time on the dosimetric treatment of Burggraeve spread rapidly, and especially did it begin to flourish in Belgium, France, Spain, Portugal, Italy, Holland, and Denmark.

The next step in the evolution of modern active-principle medication consisted in certain modifications of the original system of dosimetry, and the broadening of its scope and methods, attendant upon its introduction into America.

One of the first men in this country to become interested in the new system was Dr. W. T. Thackeray, who purchased an outfit for the manufacture of alkaloidal granules from Dr. Chartier, of Paris, and endeavored to persuade Messrs. Parke, Davis & Co., in whose employ he was, to engage in the business of manufacturing them. The firm,, however, declined to undertake it, considering the commercial difficulties in their introduction too great. Thereupon Dr. Thackeray himself formed a company for the manufacture of the granules, and started and issued a few numbers of a journal, which he called The Alkaloidal Clinic, devoted to the advocacy of dosimetric medication. However, he did not succeed in making a success of either branch of the undertaking, and the enterprise soon ended in failure.

Abbott and Waugh Enter the Lists

Not long after this, Dr. Wallace C. Abbott, then a young doctor from Vermont, who had been graduated from the Medical Department of the University of Michigan, and had located in the suburb of Ravenswood, of Chicago, who happened to have been for some time interested in the teachings of Burggraeve, began in a small way the manufacture of alkaloidal granules, in order to supply himself and also the friends whom he had interested in this subject; and, in 1894, he began the issue of a new Alkaloidal Clinic.

Dr. Abbott was a man of unbounded energy and determination, and his enthusiasm proved contagious and caused the alkaloidal idea to spread rapidly. I myself am one of those whom he interested early; and in my library I have preserved not only the first issue of Tlic Alkaloidal Clinic, but nearly every number that has followed. From that time onward, his has been the central figure in the propaganda for active-principle therapy in America, and his aphorism, "The smallest possible quantity of the best obtainable means to produce a desired therapeutic result," has been the slogan for rallying its forces to the battle.

Soon Dr. Abbott associated with himself Dr. William F. Waugh, an accomplished scholar, a successful physician and medical teacher, and a versatile and forceful writer, and who has since then shared in the work of editing The Alkaloidal Clinic — the name of which later was changed to The American Journal of Clinical Medicine as the scope of the work was broadened. These two active and brilliant men were for a time also associated in the manufacture of all the medicaments employed in alkaloidal therapy, so called; a designation, however, which in the course of years grew much broader than the term would indicate, until it has finally come to include many remedies besides the alkaloids. The present status of the method may best be stated in the language of Dr. Abbott himself, who very properly may be called the father of American active-principle medication, as Burggraeve was the originator of the earlier form of dosimetry. These are the leading principles governing the newer, more positive, more definite way of combating disease:

The Principles Governing Active-Principle Therapeutics

"1. The administration of small doses of the most active and potent known remedies at short intervals, until either remedial effect or signs of drug-sufficiency, i. e., the full physiological effect, are secured.

"2. The administration of such doses in the form of soluble granules or tablets each of which contains a definite amount of the drug.

"3.' The additional use of such solvents, eliminants, vital incitants, and local and systemic antiseptics as have proven of remedial value.

"4. The use of any and all remedial agents in the most concentrated form available that will produce definite results in recognized conditions.

"5. The avoidance of promiscuous combinations, problematical remedies, crude drugs, and nauseous, changeable alcoholic tinctures and fluid extracts when the active (remedial) principle of the drug can be obtained in its purity and given in effective, well-established doses."

Many other honored names have been associated with those of Abbott and Waugh in the building of active-principle therapy in America — a structure which is still in the process of making. Among them are those of John M. Shaller, the author of the best manual of alkaloidal medication for beginners; E. M. Epstein, who may be termed the scholar of the method ; Coleman, the persistent advocate of systemic antisepsis in the prevention and treatment of the contagious fevers; Alfred S. Burdick, the present managing editor of Clinical Medicine ; and George F. Butler. Many more names might be mentioned, in fact one hardly knows where to stop.

As to the present status of active-principle medication, it can be said that many thousand physicians are using the methods and medicaments referred to in their daily practice to a greater or less degree, and their number is each year increasing. Enthusiasm and optimism are the characteristics of these men as a class. They claim that they are better physicians because of the teachings of Burggraeve and his successors; that the principles and methods of dosimetry have enabled them to meet disease with greater confidence, and overcome its manifestations with greater certainty, than the}' were able to do with the old galenic methods.

One of my own most intimate friends, the physician through whom I got my first introduction to this newer and better method, assures me that under the uncertainties of the old system of medication he had lost all enthusiasm and nearly all interest in the practice of medicine, and was seriously contemplating changing his occupation, when, thanks to Doctor Abbott and The Alkaloidal Clinic, he was ushered into a new world in his profession, given a new confidence in his ability to help the suffering, and filled with a new enthusiasm in the practice of medicine. And I can confidently affirm, from my own knowledge of this physician, that this optimism has never left him, but that he is today a broadminded, well-balanced, optimistic, and successful practitioner, a man who believes in himself and in his power to relieve suffering and to prevent and cure disease — and these are the things which every doctor needs to believe and do.

CHAPTER II The Fundamental Laws of Active-Principle Therapeutics

LAST week I described to you the origin and growth of active-principle medication in Europe and America. Today I desire to call your attention to the fundamental laws, general principles, or elementary teachings, upon which this method of therapeutics is based.

According to my conception, these are three in number, and these three embrace all the things which are strictly essential to the method, although many other and less important peculiarities and practices have grown up around them, and of these I shall speak in my next lecture.

The Use of the Active Principles.

The first law teaches the use of the active principles in the treatment of disease.

The term "active principles," as here employed, is interpreted to include not only the alkaloids proper, but also many glucosides, resins, camphors, neutral principles, resinoids (so called), and concentrations of vegetable drugs, together with such definite chemical compounds as are sufficiently potent to produce positive results in minute doses, and of sufficient medicinal virtue to render them desirable additions to the physician's armamentarium.

This law has usually been considered not only as the first, but the most important of the three. The followers of active-principle medication are ever ready to put it to the front, and defend it as the cardinal principle of their faith and practice. If you ask them for their reasons, they will point you to the acknowledged facts that quinine is more active than Peruvian bark, atropine more positive in its effects than belladonna, morphine more definite and certain in its results than opium, pilocarpine more uniform in its effects than jaborandi, strychnine more efficient than nux vomica, and, in general, every active principle more potent, more uniform, and more reliable than the crude drug from which it is derived, or its galenic preparation.

This being the case, he holds that it is manifestly better to employ these active principles and reject the bulky residue, the inert matter, the unknown and unreliable substances whose effects cannot be predicted with any degree of certainty. For why should any part of a plant or of an animal or mineral substance which is not active be used in medicine ? Instead of choosing his remedies for their bulk, and possibly for their disagreeable qualities, as was apparently in some instances the custom in olden times, he seeks for "the smallest possible quantity of the best obtainable means to secure a desired therapeutic result/ '

Arguments in Favor of Active Principles

If we analyze the arguments in favor of the active principles, we shall find that they can be separated into three classes.

First, because, as compared with the crude drugs and their galenic preparations, they are condensed in form, minute in dose, and positive in results; containing only the active remedial principle of the drugs which they represent, and rejecting the inert material.

Secondly, because they are uniform in composition, containing, as a rule, but a single therapeutic principle, and therefore always to be be relied upon as producing the same remedial effect; whereas the crude drug may contain several unlike and even opposite principles, and these may occur in different proportions in different specimens of the drug, so that one sample of a galenic may be much stronger than another which was prepared from the same formula, and different samples similarly labeled may produce entirely different and even conflicting results. Recent analyses of standard tinctures on sale in the different drug stores of the same cities have shown a wide variation in strength, although all were supposed to contain the same percentage of the drug.

The drug-strength of a plant is affected by the character of the soil, the amount of sunshine, the temperature, and many other conditions of environment. And these may change, not only the total amount of active principles in a plant, but the relative proportions of the different principles in the same plant.

A good illustration of this fact is found in jaborandi, which contains two active principles, pilocarpine and jaborine, the one of which is the most potent of all our diaphoretics, while the other is the exact opposite, its effect being allied to that of atropine, drying up all the secretions. While under ordinary conditions the amount of jaborine is comparatively minute, and the drug jaborandi is given to promote the secretions, cases have actually occurred where it has been found to produce the opposite and undesired effect of drying up the secretions. But, if pilocarpine is used instead of jaborandi, no such effect is possible.

Keeping Qualities of These Drugs

Thirdly, they are convenient to carry, taking up but little space, and having excellent keeping qualities. These qualities render them of especial value to the country doctor who is far from his base of supplies. Dr. Robert Gray, of Pichucalco, Chiapas, Mexico, an American physician, who has practiced in the most unhealthy belt on the continent, most of the time since the close of the Civil War, writes as follows of his own experience.

"I carry one hundred and fifty-six active principles, weighing less than five pounds with case, the equivalent of which in galenic forms would load two mules. I am never ambushed by the enemy when suddenly confronted by some desperate emergency, no matter what the disease or the complications may be. I have the antidote while the time for medication still remains, and do not have to send prescriptions to a. distant drug store for uncertain remedies, a makeshif e often fatal to an imperiled life. ' '

As for the keeping qualities of the active-principle medicaments, they are due in part to the chemical qualities of the alkaloids themselves and in part to the manner in which they are held together in the standard granule, which is Well known to preserve the medicaments much better, than any kind of coating that can be applied to a pill or a tablet. This is well seen in the case of calcium sulphide, a drug that is almost certain to deteriorate by keeping when prepared in the ordinary tablet or pill form. Here the superiority of the standard granules over the other preparations is very marked.

While we believe in the superiority of the active principles, as a general rule, cases no doubt are encountered in which better results can be obtained from crude drugs and their galenical preparations, as well as from the coal-tar preparations and other chemical products. When this is so, they should be used without hesitation. In the words of Shaller, who is one of the first authorities on active-principle medication in America, "Any remedy that is good and that cures is used, no matter what its source or by what school it has been first advocated." The greatest need of the doctor is, not the active principles, but definite therapeutics, no matter whether it be in the direction of galenic medication, biochemistry, specific medication, serum treatment, or glandular therapy.