it invades all parts of the body, and the systemic distribution is often maintained for many days after it has been discontinued, through the hepatic storage of the remedy. There can be no doubt that the nervous system can be powerfully influenced by such a process of medication. No at The relation arsenic has to strychnine is another interesting feature in the prescription. The latter comes in as a nerve tonic of a positive nature, but in its physiological action as such, owing to the time of its elimination, it is but secondary to the former. Here, it appears arsenic serves as a synergistic to strychnine. The sedatives in the formula run a different but an indispensable course of their own; they are to give immediate relief and to facilitate the cure by keeping the nervous erethism in subjection, both pathologically and therapeutically, until the tonics have performed their legitimate work. It might be said that the pathology of neuralgia is not clearly manifested in the prescription, therefore its polypharmic complication. tempt could be made in that direction in this case, as the treatment indicated in the prescription was strictly symptomatic. As the symptoms of the disease are complicated, there must be a corresponding complication in the prescription indicated. The pain alone in the disease, which so absorbingly occupies the attention of the patient, has nothing to do with its etiology; but may serve as one of the causes to keep up a continuation of the disease; therefore it is of the greatest importance to jugulate the pain by treatment, not only to promote the comfort of the patient, but to destroy the initiatory element of inflammation. When we speak of a complication in the prescription, there is discerned, nevertheless, harmony in the operation of the different ingredients on the system. Quinine stands to give immediate support, strychnine as a powerful auxiliary to it, arsenic to give it durability, and the sedatives to guard against pain, irritability and idiosyncracies. This prescription can likewise be advantageously applied in cases for which it was not originally intended on fixed therapeutic principles. If a combination of many remedies are at times necessary to subdue a disease, it likewise occurs not infrequently that a train of symptoms can be successfully followed up by a single remedy. For example: B Pulveris Ipecacuanhæ Divide into 10 powders. gr. xx. What is the nature of the case? Evidently a lesion of the mucous surface. Let us report a hypothetical case. The patient has a dry cough, is bilious, dyspeptic, has anorexia, tympanitis, and constipation, alternating with dysenteric discharges. He has some fever, or rather hot flashes with a hot dry skin. Urine scant and high colored. He is likewise annoyed with a dull headache, sleeps poorly and is easily fatigued, etc. What therapeutical remedy is here required? An expectorant, laxative, alterative, diaphoretic, febrifuge, sedative and tonic. Any simple rem edy having these medical properties, judiciously administered, would very likely soon effect a cure. Here ipecac alone would meet all these indications, complicated as the case may appear. The face of this shows a very simple treatment. But the science of it lies in a profound therapeutic and pathological knowledge of the remedy and the disease. The physician, who attempts to meet the indications of disease with a polypharmic prescription, when a single remedy will serve a better purpose, will but exhibit confusion and want of judgment. In the surgical writings of the late Prof. S. D. Gross, single remedies are frequently recommended in the management even of grave and complicated cases. When he says an aperient is the most reliable remedy for incipient hipdisease, and gave his prescription, which called only for a simple domestic remedy, he revealed a lore surpassing that we attempted to trace in his famous prescription above. The manifold physiological effects of a laxative, bearing di rectly and indirectly on the morbid action, no doubt were all taken into consideration in the case. If we cannot too far laud the virtue of a well applied simple prescription, neither can we always condemn that of a complex character. Both kinds are to be measured by the nature of the cases for which they are intended. Thus, epilepsy we are apt to treat with a complicated formula, but not so typhoid fever. There is a rule to be observed in writing the two kinds of prescriptions, the one with a symptomatic, and the other a pathological basis. A simple prescription is based on a pathological fact, while the other is more or less based on the symptoms of the case. If we have no pathological data to go upon, such that at least can be successfully combated by medicines, what else have we to be guided by but the symptoms of the disease? Symptomatology alone is apt to lead us into polypharmacy. But even where the nature of the disease is well understood, as in some incurable diseases, as cancer, the last stages of phthisis, etc., and we are obliged to let go our grip on a curative treatment, the treatment then becomes strictly symptomatic, and often complicated to meet a complicated train of symp toms. The Art of Combining Remedies. In practice certain principles should not be lost sight of. Chief of these, are to prescribe as few remedies as possible, and to use no powerful drug without a very distinct idea of what it is intended to do. Whenever it is desirable to give a powerful remedy, in increasing doses until its physiological effects is produced, it should always be given by itself. Thus, it may be necessary to give arsenic, to impress the system at the same time that iron is indicated; but the two remedies should be given separately, so that the dose of either can be increased or diminished independently of the other.* The principles of combination may be summed up as follows: I. To augment, correct, or modify the action *Prof. H. C. Wood. of a medicine. Thus, purgatives act much more kindly, when a number of them are united together. The chief reason of this, probably, is, that as different remedies affect different por tions of the gut, the whole intestine is best reached by a union of the diverse substances. It may take an intense irritation of the mucous membrane to purge as actively as does a mild irritation of both the mucous membrane and the muscular coat. There are powerful medicines which act similarly upon some parts of the organism but dissimilarly upon other parts. By combining such remedies powerful effects can be obtained at the points where the two lines of action cross each other, without influencing to a great extent other portions of the system. Thus, chloral produces sleep by its action upon the brain, and also has a distinct influence upon the heart, but none upon the intestinal tract. Morphine acts upon the brain, and does not influence the heart, but has a powerful effect upon the intestinal tract. By combining chloral and morphine we get an overwhelming conjoined influence upon the brain, producing sleep, with the least possible disturbance of the heart and of the intestinal tract. 2. To obtain the joint action of two or more diverse remedies. Thus, in a cough mixture, morphine may be included to quiet the cough, while ipecac and squill (in accordance with the first principle) are added to affect the mucous membrane. The application of this principle requires caution, or the practitioner will be led into "that chief abomination," polypharmacy. It is worse than futile to attempt to prescribe for every symptom. It is the underlying cause of the disorder, or the understratum of bodily condition, which must be sought out and prescribed for simply. 3. To obtain a special combination which is really a new remedy, or which experience has shown acts almost as a new remedy. Thus, when to iodide of potassium in solution, corrosive sublimate is added, a new chemical compound is formed, which experience has shown to be of great value in syphilitic diseases. Griffith's anti-hectic mixture is another instance of the use of chemical changes, the proto carbonate of iron being formed out of the sulphate of the metal and the carbonate of potassium. In the famous Dover's powder no chemical change occurs, but the ordinary action of opium upon the skin is so enhanced that the combination may be looked upon almost as a new remedy. 4. To afford a suitable form. Thus, acacia is added to make an emulsion, or confection of rose to make a pill. In the choice of excipients, care should be exercised in selecting a substance free from medical properties, having no chemical incompatibility with the medical agent and of suitable physical character. Bread crumbs often make a good basis for pills, but with nitrate of silver they are chemically incompatible on account of the chlorides in them. When writing a prescription, the utmost care should be taken to use such excipients that the combination shall not only be attractive to the eye, but also as little repulsive to the palate as may be.* Incompatibles. In combining remedies, the subject of incompatibilities must never be lost sight of. These are two in number-physiological and chemical. The first of these it would require large space to discuss fully, but the intelligent practitioner can readily make all necessary deduction. It will suffice here, to point out certain principles, and a few special reactions. Soluble Salts which can by mutual decomposition form an insoluble compound, will undergo such decomposition when they meet in solution, and will precipitate, unless in some very rare instances, in which a double salt is formed. Soluble Salts which are not capable of forming an insoluble salt, never precipitate, and rarely undergo decomposition when they meet in solution. Mineral Acids decompose salts of the weaker (carbonic, acetic, etc.,) acids, and form ethers with alcohol and alcoholic preparations. Alkalies precipitate the alkaloids and the soluble non-alkaline metallic salts. Glucosides, such as santonin and colocynthin, should not be prescribed with free acids or emulsion. Tannic Acid, and all substances containing it, are incompatible with alkaloids and drugs concontaining them, with albumen and gelatin, and with most soluble metallic salts used in medicine. Iodine and Iodides are incompatible with the alkaloids and the substances containing them, as well as with most soluble metallic salts. The iodide of potassium should always be prescribed alone, or only in combination with corrosive sublimate (with which it forms a double salt), or with iodine itself. Tinctures, and other Alcoholic Preparations containing resin, precipitate the latter when water is added. Nitrate of Silver should always be prescribed alone, or in company with opium, or extract of hyoscyamus only. Most vegetable extracts decompose it, and with creasote, it is said to make an explosive compound. Corrosive Sublimate is incompatible with almost everything, and should be given in simple syrup; even the compound syrup of sarsaparilla is said to decompose it. Syrup of Squill, containing acetic acid, is incompatible with carbonate of ammonium, but not with the chloride. Acetate and subacetate of lead are incompatible with almost every thing, but are, nevertheless, frequently used in lotion with opium, the insoluble compound formed being therapeutically active. Vegetable infusions are generally incompatible with metallic salts. * Poisonous compounds may be formed by the admixture of many substances in solution, such as Potassium chlorate with potassium iodide in solution together do not react at ordinary temperature, but in the system they evolve a poisonous agent, probably the iodate of potassium. *Prof. H. C. Wood. Potassium chlorate with syrup of iodide of iron, liberates iodine from the iodide in the warm stomach, causing severe gastric irritation, perhaps gastritis of a dangerous degree. Dilute hydrocyanic acid, or potassium cyanide, with calomel, forms the bichloride and bicyanide of mercury, both virulent poisons;with metallic hydrates, carbonates, sub-nitrates or sub-chlorides, cyanides of the metals are formed which are even more poisonous than the acid itself in its usual diluted form.* On Synergistics. The synergistic action of remedies is the superstructure of most of our medical prescriptions. Its action is co-operative with the principal agent you may have decided to employ. There are accessory, or secondary substances which act the part of medical adjuvants. These substances serve, for instance, to aid in the solution, transformation, and chemical metamorphoses of the substances destined to be absorbed, and consequently favor their absorption. Thus, acids serve to favor the solution of bases, and reciprocally the bases that of the acids. Another condition in which secondary or accessory substances may add something to the effect of the principal substance, is, when these ingredients, although having less effect than the principal substance act exactly in the same manner, and are true synergies, adding to the effect of the principal substance.t The physiological force of a remedy is not always a factor in the character of a synergistic. Even water may serve as such. For example: the physiological action of water internally, is to hasten the metamorphoses of tissue, and increase the urinary and cutaneous secretions. Its action upon the kidneys and bowels is increased by salines, upon the skin by sulphur, upon the blood by iron.‡ Cam The synergia of a substance may be applied to augment the power of the basis in a formula, or to make more acceptable its effects. Under this principle morphine and atropia, or opium and belladonna are combined in the treatinent of pain. Guarana, in a cup of strong tea, for headache. Canabis indica, with bromide of potassium, in insane delirium. The sulphate of iron to increase the purgative powers of aloes, or to combine ipecac with aloes to prevent its irritating effects upon the anus. phor has a wide range as a synergistic-with opium in the treatment of diarrhoea and other diseases-with aloes to render its action more certain and less irritating—with cantharidin it renders protection to the kidneys. Nearly all the narcotics unite with characteristic effects. Conium and hyoscyanus have an action of their own; the same with opium and conium, and conium with belladonna. The combination of opium and hyoscyamus is said to form the most powerful of narcotic combinations.|| The protective synergia characterizes many of our medical formulas, as forcibly illustrated by uniting carbonate, or spirits of ammonia, with iodide potassium, to prevent or control the symptoms of iodism. Chloral to moderate the violent effects of strychnine, and even to serve as an antidote to its poisonous effects. The same might be said of opium, to hold in check the toxic force of veratria. Sometimes this class of synergia is given alternately with some powerful remedy; as when ammonia is administered by inhalation during chloroform-anææsthesia to prevent heart failure. Sometimes a synergistic alone may determine the physiological effects of a remedy. Digitalis may fail to act as a diuretic until combined with bicarbonate of ammonia, or with squills. The infusion should not be chosen as a cardiac remedy, nor the alcoholic preparation when diuretic action is desired.* Even the infusion of digitalis, prepared from the fluid extract, as a rule, may be devoid of diuretic effects.* There is hardly any more interesting and more important feature in the practice, than the use of synergia to aid the physiological resistance, in preventing dangerous complications in formidable diseases. Prophylactics, in the common sense, might be included, but here we take it from a different standpoint. In typhoid fever there may be a fatal tendency by the intervention of pneumonia, or perforation of the intestines. In adynamic malarial fever, of hemorrhage. In many forms of malignant fever by excessive vomiting, etc. In such diseases, in particular, when of an epidemic form, a synergistic treatment should be enforced at the earliest stage of the disease. You, really, must prescribe for, what you may expect to happen in the future. For, to prevent pneumonia in typhoid fever, give ipecac for the first cough, slight as it may be, and at the same time to protect the bowels from ulceration, without waiting for any unfavorable symptoms to come. In epidemic diseases, where hemorrhage is usually a fatal complication, give turpentine at the very beginning of the disease, and do not wait for the bleeding, which nothing then can stop, as it usually goes hand in hand with collapse. By this system of medication the patient can be often fortified in synergism with the regular treatment of many serious diseases with the happiest effects. In an epidemic of a malignant form of typhoid fever that raged in central Illinois, nearly all the fatal cases died from the effects of an uncontrollable hemorrhage of some kind. In consultation I advised that cases of fever of recent occurrence be put on hæmostatics, as gallic acid and turpentine, synergistic to a sustaining treatment, with the happy result of no further loss of a single patient. † In an epidemic of malignant gastritis (following an epidemic of erysipelas) in central Ohio, it appeared that excessive vomiting tended to the fatality of the disease. consultation, muriated tincture of iron with hydrocycanic acid were recommended to be given to head off the vomiting. The remedy mitigated the disease at once, and even in advanced cases recovery ensued. † Special pains *Dr. F. A. Castle. In †Dr. G. P. Hachenberg, Cincinnati Medical News, 1880, p. 600. seems, in place, here to impress upon medical readers the importance of this question, involving as it does the golden rule: "It is better to prevent than to cure. Antagonism of Drugs. The number of antagonists is immense.† We will not consider here the dynamic antagonism of antidotes to poisons, or the chemical errors that may find their way into some of the medical prescriptions in the form of incompatibles. It is only in its therapeutical bearing we solicit your attention to the subject. It is physiologically demonstrated in that existing between jaborandi and belladonna. When the heart has been slowed or arrested by jaborandi, atropia will bring the rate of pulsation almost to its normal action; the reverse of this occurs, provided the amount of atropia previously applied has not been too great. Upon the sweat-glands the two drugs have also antagonistic powers, one being able to annul the action of the other. The same is true in regard to the salivary secretions, and the intestines and pupils. In belladonna poisoning, the alkaloid has been used with no advantage in very small doses; but in a case in which 9-10 of a grain of atropia had been taken, 9 grains of pilocarpine are said to have been injected hypodermically in between one and two hours with success. The antagonism between chloral and strychnine is also one of great energy, as their effects have been observed on animals. The intercurrent administration of strychnia and chloral to an animal, of a large and even dangerous dose of chloral, a dose of strychnia five or six times the ordinary medium dose, may be safely administered, and even a dose of either drug which is fatal to the same species and size of animal, is not usually followed by death.** Physostigma is likewise antagonistic to strychnia,-as an agent that powerfully diminishes the reflex activity of the spinal cord, it has been used with success in a case of traumatic tetanus. tt The antagonism between morphia and atropia mainly affects the cerebrum, the latter destroying the unpleasant effects of the former. The combination of the two make an excellent remedy for the treatment of pain-hypodermically, in neuralgia and other painful affections,—in suppositories, in cases of diseases of the bladder or generative organs. On the eye the two agents in question are mutually antagonistic, but atropia continues to act for a much longer time than imorphia. Atropia does not constipate, and may even relax the bowels; morphia has a reverse tendency. As regards toxic effects upon the cerebral organs, the two agents are materially antidotal, but this antagonism does not prevail throughout the whole range of their influence, so that, in some respects, they do not counteract one another, while, as concerns one organ, the bladder, both seem to affect it in a similar Way.* The toxic application of calcium chloride on the detached ventricle of the frog's heart can be quite antagonized by a toxic dose of potassium chloride, and vice versa, a toxic dose of potassium chloride, sufficient not only to arrest the spontaneous beats, but sufficient to prevent a strong induction shock exciting any contraction, can be antagonized entirely by a toxic dose of calcium chloride, and by the careful appointment of the two salts their antagonism be so nicely balanced that the ventricle will beat spontaneously and quite naturally. A toxic dose of potassium chloride will antagonize a toxic dose of veratria, and vice versa, a toxic dose of veratia will antagonize a toxic dose of potassium chloride, and these two substances may be given with such equipoise as completely to antagonize each other, so that the ventricle will beat quite naturally and spontaneously; but if one salt were administered singly it would powerfully affect the function of the ventricle to an extent incompatible with life.† Therapeutically, the most interesting part of this subject is to secure an independent action in the conbination of two antagonistics. This is manifested in some of the salts, and many prescriptions are based on this principle, as morphine combined with atrophine, quinine with hydrobromic acid, and chloral with opium, etc. Such combinations are to give either intensity or moderation to the remedy, The following_table shows the most important examples of antagonism of drugs: Aconitine Alcohol Ammonium chloride 66 Barium Bromal hydrate ||H. Larvand. **Prof. R. T. Edes. *S. Weir Mitchell Atropine. Strychnine. There may also be an antagonism between diseases, one destroying the force of another. This is not only the case in the effects of counter-irritants, or any other medical disease enforced as a remedial agent; but it may exist between two violent constitutional diseases, evidently caused by the antagonism of two sorts of micro-organism. Thus the inoculation of an erysipelatous virus in the submaxillary region of the diphtheritic patient, has resulted in a prompt cure of the sufferer. There is, evidently a great field for experimentation in this direction, before us; Koch himself already taking the lead. The economy itself may reveal antagonism between two organs under the action of medicine. There certainly is a very marked antago nism between the bowels and the kidneys; so that free catharsis reduces, very decidedly, the secretions of the urine. There is also an antagonistic relation between the skin and the kidneys, so that an increase in the excretion from one of these, generally results in a diminution of that of the other emunctory. Mode of Administering Medicines. Medicines may be administered by the mouth, by the rectum, hypodermically, by inhalation, by inunction, by medicated baths, and as remedial agents we may add: electricity, massage, and a special adaptation of diet, climate, recreation, rest, exercise, and labor, and we may class as important among the latter, salutary mental influences. Babtchisky Prof. H. C. Wood. On the Forces of Medicine. What demands our first consideration in administering a dose of medicine, aside of its physiological applicability, is an estimate we have to make of its dynamic force. We can do this systematically, in a measure, on a scale from 1 to 100, as represented in the table of Therapeutics in this work. The higher the number the more powerful the remedy, and as the numbers run lower, the milder in force. This estimate of the force of a medicine is more cautionary than arbitrary. Many circumstances may intervene to change its status given in the table, in particular in many forms of sickness, in idiosyncracies, and by a combination with other remedies, etc. But on a general physiological basis the scale is exceedingly convenient, and a safe guide to go by for any consultant in administering a remedy for the first time. In estimating the dynamic force of a prescription we must observe it, independent of its component parts. For example, chloral stands at 8o, and iodide of potassium at 60. The combination of the two would give it a place in the scale of deadly poisons. Where carbonate of ammonia, at a force of 55, and iodide of potassium, at 60, are com bined, the ammonia will not materially lessen its force, but the iodide will be changed, even to the extent of destroying all tendency to iodism. Suppose we administer opium at 85, in connection with iodide of potassium at 60. Both would be somewhat augmented in force. Here opium stands with equal force with chloral, but not in combination with other medicines, but as two independent agents. Let us take chloral in connection with strychnine at 96. As these are antagonistic in their physiological effects, in combinination they both greatly lose force. The same is the case with belladonna and opium, and many other remedies. Corrosive sublimate and opium united are mutually augmented in force, and so are arsenic and tobacco. Now, The question naturally arises, where is the pharmaco-dynamic action of a medicine centred? Let us take quinine, at 70, to solve this question. Quinine, in small quantities, stands preeminent as a tonic or stimulant, and it is also just as true that in large doses it outranks every other article of the materia medica in reducing exalted temperature of the body. there are, in some respects, two opposite, or, at least, altogether different pathological conditions, for the alleviation of which it is administered, in the former case to revive falling activity, and in the latter to depress activity.* According to our formula, the given force is manifested in the administration of the remedy tending to cinchonism. Few, if any, therapeutic agents are characterized by but a single mode of action, but produce effects in keeping with the quantity, administered or applied, and the con dition of the body at such a time,* neither is the elementary composition of drugs sufficient to explain the properties of medicaments and their diversity of action. Perhaps the relative molecular structure alone, between the medicine administered and its organ of selection in the *Dr. Thomas J. Mays. |