animal body is the source of its force in whatever degree it may be manifested. This theory would explain why some drugs are highly poisonous to some animal life, and to that of others perfectly harmless.

The legitimate force of a remedy cannot be produced without the aid of a physiological force to meet it. It is impossible to induce emesis in subjects who are in an adynamic state, † and in a state of profound collapse, the stomach will accept nothing for assimilation and absorption.

The effects of remedial agents are more intense when the economy is already turned in the direction towards which the medicaments tend to impel it, the effects, on the contrary, are less intense, or what amounts to the same, tolerance is greatest when the economy is turned in the direction opposed to that towards which the remedial agent has a tendency to impel it. †

It is important to seek an explanation of the circumstances which cause variation in the physiological and remedial effects. There are two principal causes for the variations of action; the first is the power of the agent itself, which varies in different cases and under different circumstances; the second is the ensemble of phenomena as regards the organism.†

The peculiar power of a remedial agent is not an expression having always the same significance; it does not signify that a medicament is always endowed with the same virtues, and in the same degree, and that it can always exercise a calming or stimulating action. The peculiar properties possessed by the remedial agent are not thus in relation with the particular conditions of pharmaco-dynamic energy possessed by or inherent in it.†

The physiological vital force necessary to manifest the dynamic action of a drug, whether molecular or chemical, or both, in combination are but depending operations in that simple chemical process of the action of oxygen carbon and hydrogen, which is so intense in its effects that nearly all the force which is generated outside and inside of the body results from its chemical combination.

In admitting a scale giving the power of a remedy, it is likewise admissible to make an estimate on the constitutional condition of the patient: let I stand for general good health and 100 for death, the intervening numerals giving the different degrees of constitutional impairment. We will show the importance of both of these scales-the one physiological and the other pathological-in another part of the book.

Chemical Changes of Medicine in the Stomach.

There are few remedies that are not materially changed when introduced into the stomach. Therefore it is of frequent occurrence that medicines are not admitted into the system as represented in a prescription. One ingredient may modify the other, as opium and acetate of lead. They act chemically on each other in the stomach, producing the acetate of morphic

†Prof. Adolph Gubler.

and meconate. As a rule, when medicine is taken into the system a series of chemical changes ensue from the moment of its ingestion to the period of its elimination. This is effected by its coming in contact with the acids, alkalies, and alkaline chlorides, and other chemical constituents that have their habitation in different parts of the system. Owing to the systemic changes in health and disease, in fasting and feasting, and other circumstances, these chemical reactions likewise meet with corresponding changes. If these systemic chemicophysiological operations were always the same, there would be no change in the vital forces, and medicine could be administered with uniform results. The frequency and extent of these systemic chemical oscillations may not always receive the proper attention, and therefore may cause confusion in theory and disappointment in practice. M. Andrel considers mucus to be acid; Booth believes it to be alkaline. The former thinks the pancreatic juice alkaline, and Turner has it acid. Such are the discrepancies we find as to the chemical nature of nearly all the secretions of the human body. The fact is, they may be all right, under peculiar circumstances. It is known that the secretions of the mouth may be alkaline after food is taken, acid, and even poisonous after fasting; the urine may be acid, and then alkaline, or acid in the kidneys, and alkaline in the bladder; the chyle may be acid in the small intestines, but is alka line in the lacteals; sweat is acid, but from a skin in a state of inflammation it becomes alkaline, etc.

It is in these chemico physiological changes that many of the inequalities are produced in the effects of medicine--why it is that one remedy will give a marvelous relief in one case, while in another, apparently with the same pathogenic condition and the same constitution, may prove the instrumentality of harm.

The first, and often the most important chemical change that a medicine undergoes in the stomach, is in its contact with the lactic, chlorhydric or phosphoric acids, or its normal and abnormal ferments. Some are made soluble, and form a close affinity with the acid secretions of the stomach and its contents, some bear no modification whatever, others pass through a decomposition into a new compound.

With

The acids in the stomach exert great influence. They increase the solubility of salts, for the majority of salts are rendered more soluble by an excess of acid. Bases are also salified by those acids. Thus, the oxides of iron, of zinc, and of calcium are salified and dissolved by the acids contained in the stomach. regard to iron, this is of great importance, because we very frequently introduce oxides of iron, relying upon the acids in the stomach to effect their solution and procure their passage into their circulation. The acids in the stomach also decompose such carbonates as those of lime, soda, potash, magnesia, and iron rust. Consider how important are these facts. When you desire to diminish the gases and acids of the stomach, you must not prescribe carbonate of magnesia, but calcined magnesia. The car

bonates would only have a tendency to increase the disorder by producing carbonic acid gas.* A most important feature of medicines in the stomach is their conversion into new compounds. Thus, the cyanide of potassium is converted into prussic acid. The nitrate of silver into a chloride. The citrate of bismuth and ammonia is precipitated by the hydrochlo ric acid, which it meets in the gastric juice, and is consequently reduced to the condition of the insoluble salts of the subnitrate and subcarbonate. The therapeutic doses of permanganate of potassium are entirely decomposed in a very short time after they reach the stomach, hence any action which the drug exerts upon the general system is due to the oxide of manganese; indeed, the ordinary black oxide of manganese is affirmed by different practitioners to be as active an emmenagague as is the permanganate.

When the oxide of zinc absorbs lactic or hydrochloric acids in the stomach, the chloride of zinc is then formed, which is a salt possessed of highly irritating, nauseating and emetic qualities; therefore the oxide of zinc should be associated with bicarbonate of soda, that the acids from the stomach may be more speedily absorbed. Many forms of iron undergo a change to ferreous chloride before being absorbed in the hydrochloric acid of the gastric juice, while others, like the ferric salts, undergo a partial reduction. Bromine and iodine are much alike in their chemical changes in passing through the system. The bromine in an uncombined form unites with the soda or potassa found in the secretions of the body, forming a neutral salt of bromide, or bromide of sodium or potassium. The efficacy of iodine is greatly impaired by all starchy food, and should be administered before eating, unless to neutralize its irritating effects on the stomach. The sulphites taken internally are not decomposed in the stomach ordinarily. If otherwise, there is a manifest production of sulphurous acid gas, when a little magnesia should be added to the sulphite to neutralize the acids of the stomach. Sulphites are readily absorbed, and appear in the urine unchanged in about twenty minutes after they have been swallowed; but they are readily changed in the system into sulphates.

The Time for the Administration of Certain Medicines.

Taking into consideration the reacting influences between a medicine introduced into the stomach and the secretions of that organ, we are led to inquire, when is the most propitious time to introduce a medicine into the stomach, fasting or at meal time? On the authority of Gubler: "The only remedies introduced at meal times are those requiring previous dissolution, those acting in the same as histogenics, and metallic substances from which the metal is alone desired, such as iron, manganese and

*Prof. Adolph Gubler. †Prof. R. T. Edes. Prof. H. C. Wood.

Waring.

Prof. Adolph Gubler.

arsenic. Organic substances, as a rule, are usually administered on an empty stomach." A better rule is, that nearly all remedies of a high power, or of a heterogeneous nature, had best be given on a full stomach. Take any powerful medicine, it will not always have the same effect by giving it either way. Strychnine in a maximum dose, on an empty stomach, may readily manifest its toxic influence, but it would take more than double the dose to secure the same effect by giving it after eating. The difference is, that medicine taken before or after eating is not disposed of by the same physiological operation, ‘A medicine administered after eating finds its way gradually into the system, through the ordinary process of assimilation, and often with better effect, with a less toxic tendency or intolerance than when taken on an empty stomach. A soluble medicine in an empty stomach is rapidly absorbed by the veins of that organ, or rather by endosmosis. It is obvious that medicines administered before and after eating do not find their way into the circulation by the same avenues, and by the same physiological action; and the effect of a medicine introduced into the system, either by a gradual or rapid process, may be a question of the greatest importance in a clinical point of view.

To show that remedies at different times have different effects in connection with eating, we have simply to cite the effects of bicarbonate of potassium and other alkaline carbonates on the stomach-on an empty stomach they increase the acidity of the system, while their administration after a meal diminishes it.

Iodine and iodides should be given on an empty stomach, If given during digestion, the

acids and starch alter and weaken their action. Acid, as a rule, should be given between meals; acids given before meals check the excessive secretions of the acids of the gastric juice. Oxide and nitrate of silver should be given after the process of digestion is ended. If given during or close after meals, the chemicals destroy or impair their action. Potassium permanganate also should not be given until the process of digestion is ended, inasmuch as organic matter decomposes it, and renders it inert. Malt extracts, cod liver oil, the phosphates, etc., should be given with or directly after food.*

There are other considerations why a proper time should be selected in giving medicines in relation with eating. It is known that various preparations possess the power of precipitating the peptones of food, or of destroying the activity of pepsin, such as corrosive sublimate, alcohol, tannin, etc., and these should be, therefore, ordered to be taken between, rather than just before a meal.† This should be carefully remembered in the treatment of adynamia, and where it is of the utmost importance to maintain a normal gastric digestion. We have not only to foster gastric digestion, but to make our best efforts to restore it when depressed by some constitutional disease; this is better accomplished by medicating more for the disease, than the

*Gaillard's Medical Journal. †Waring.

functional derangement it may cause in the stomach. It is well known that in impaired digestion and deficient interstitial nutrition, accompanying certain blood diseases, which produce anæmia, or a diminution of the red blood corpuscles, for instance, the syphilitic and cancerous cachexia, iron will not, as a rule, repair the anæmic condition while in the former disease, certainly mercury and iodide of potassium, and in the latter sometimes, carbonate of ammonia or potassa will improve the anæmia.*

Avenues of Introduction of Medicines.

When a substance in a soluble state is brought in contact with almost any part of the human body, internally as well as externally, more or less of it is taken into the general system by ab sorption. All parts are not equally active in absorption, neither can all parts be used with safety to the patient. The mucous surface is the most available part for the reception of medicines into the system. The absorbents of the serous membrane will admit medicines; but it can hardly ever be resorted to, owing to its great sensibility, and tendency to a violent dangerous inflammation when foreign bodies are brought in contact with it; this is in particular the case with the peritoneum. The skin is frequently the seat of application by which medicines are administered, in the form of baths, unctions and under clothing impregnated with medicine. The skin is in remarkable contrast with the nature and function of the serous tissue; so blunt in its sensibility, that it is the place of selection for all powerful counter irritants. The skin being an emunctory, and subject to many forms of disease, may not only be treated topically, but constitutionally, the medicine often making its salutary impression in the process of elimination. Sulphur, arsenic, iodine, etc., become curative in many forms of cutaneous disease in this manner.

The place of application and avenue of introduction of a remedy are two things which are often confounded. A solution of benzoate of soda may be atomized, and inhaled, and absorbed into the system, and eliminated by the kidneys as hippuric acid. The same solution may be taken into the stomach, or introduced into the rectum, with the same effect. Here we have an example of three imposing entrances of a substance into the system, leading to the kidneys.

Camphor may be absorbed from the mucous membrane from any point, to be eliminated by the lungs and the skin. When taken into the system by inhalation, it goes the rounds of the

*Prof. Rob. L. Edes.

†G. P. Hachenberg, M. D., on Important Points in Surgery, Cincinnati Medical News, Vol. IX., No. 9.

†G. P. Hachenberg, M. D., on Dermic Medication, Medical Record, 1877.

†G. P. Hachenberg, M. D., Under-clothing Impregnated with Medicines, Western Lancet, Vol. XIII., p. 21.

Jaccoud.

circulation, as if it had been taken into the stomach, and then eliminated at the point of introduction. There is no special rule to determine the avenues of introduction of medicines, except in their terminal physiological effects and process of elimination. Every drug of any perturbation has pretty much a route of its own in its transition through the systemwe judge this to be so, from its effects.

The place and manner of application may be ever so varied. Iodoform is absorbed from the stomach, and so from any raw surface. Medical substances may be introduced in parenchymas, then again, in deep seated regions, as in deep seated cellular tissue of a limb, in the ganglions, and the thyroid glandt-a system of treatment called the method of parenchymatous substitution. But even in these instances, each remedy thus applied will follow its legitimate route through the system.

Chemical Alterations which Medicines Undergo.

A chemical change of a medicine may occur, even before its administration, through such influences as heat, light, moisture, and spontaneous decomposition. In the saccharated iodide of iron the addition of sugar is for the purpose of preserving the iodides from decomposition, but when exposed to sunlight the iodide is reduced to the condition of a subiodide.

When organic substances are introduced into the stomach, if there be considerable gastric activity, as for example, during the digestive process, they will meet with such important changes, that it may happen their effects will be greatly, if not entirely, impaired. You introduce aconite but obtain no results, not even with high doses. Atropine and morphine are subjected to the same destruction. Even quinine and the proximate alkaloids, which are so persistent, are not able to resist being modified, so that at meal time considerable quantities can be taken, without obtaining the desired result. In the stomach oxygen is also found. It has the effect of raising substances from a low to a higher degree of oxidation, which is what happens with sulphate or carbonate of protoxide of iron. It is converted into a sulphate of the peroxide of iron, which becomes basic. There is an ulterior oxidation, and a change to a higher condition. This free oxygen oxidizes all substances introduced, either at a low state of oxidation or absolutely free. Thus, if sulphurous acid is introduced, it has been suggested that it will be changed into sulphuric acid. When phosphorus is introduced into the stomach it passes to a higher degree of oxidation, and also undergoes other mutations due to the presence of water. Phosphorus decomposes water, and forms on the one hand phosphorus acid, and on the other phosphuretted hydrogen.* The hypophosphites probably all become oxidized in their passage through the alimentary canal. It is from the phosphites and not from the phosphates we derive the beneficial

action of phosphorus in promoting healthy functions.†

Permanganate of potassium is supposed to act by oxidizing the blood.‡

When carbolic acid is taken in maximum doses, it is in part eliminated as carbolic acid, and the remainder of it in part escapes in combination with an alkali as sulphur-carbolic and glyco-uronic acids, and is in part oxidized in the system.

Iodine seems to be eliminated, partly as an alkaline iodide and partly in organic combination. ¡

Virchow says: "If we follow the chemical changes and action which iodide of potassium must necessarily undergo and exercise in its passage through the circulation, it is to be noted that it undergoes no change in the stomach, for whilst on the one hand, the extremely dilute hydrochloric acid of the gastric juice is incapable of decomposing it, so on the other it neither precipitates nor is decomposed by the albuminous compounds, sugar, starch, and salts, that are or may be present in that organ. It then enters the blood by diffusion in an altered state; but, even were the iodide decomposed by the hydrochloric acid of the gastric juice to some extent, it would only result in the entrance of hydriodic acid instead of iodide of potassium into the blood, the action of which would be similat. The large quantities of carbonic acid, which are continuously produced in the blood, will immediately act on the very dilute solution of the iodide in the blood, especially at the high pressure under which the gas exists in the blood. Hydriodic acid is set free with the formation of the bicarbonate of the alkali. The acid is, however, immediately broken into iodine and water. Thus, by the direct action of the oxygen of the blood upon the iodide of potassium, iodine must be set free. The action of iodine de

pends, like that of bromine and chlorine, upon its affinity for hydrogen, which it displaces from the compound, and unites with to form free hydriodic acid. The molecule of hydrogen withdrawn from the compound, is at the same time, replaced by one of iodine; but this new compound, being unstable, immediately breaks up, and the secondary products readily undergo oxidation. In the same way the hydriodic acid dissolving in the blood, itself undergoes oxidation, and the iodine is again set free to pass through the series of changes. A single molecule of iodine may thus aid in the decomposition of many molecules of organic matter, which explains the action of small doses of it."

The sulphite of potassium is in part decomposed when introduced into the blood; it is excreted, in part, in the state of sulphate of potassa, that is, the sulphur has become sulphuric acid, and, in this state, has induced the formation of sulphate of potassa, which is thus excreted in the urine.* Tannic acid splits up into gallic acid and glycol; it simply takes up water to add the necessary quantity of hydrogen and

Thomas S. Mays. *Waring.

Prof. H. C. Wood.
Prof. See.

oxygen to that which is already contained. All essential oils which are resinified, and which passing to the state of oxides, combine with the acids and become true salts, and will pass in large part by the urinary passages.

*

When nitrate of silver is mixed with bread crumbs, or bread in the stomach, in a very few moments the silver is reduced and chloride or albuminate of silver is formed. More than seveneighths of the nitrate of silver is thus decomposed into metallic silver. The soluble salts introduced into the primæ viæ where they meet with chloide of sodium, form insoluble salts-the organic salts combine with potassa or soda, so when citric acid is administered, carbonate of soda is eliminated from the kidneys.

As a consequence of the action of the pancreatic juice, salol splits up into carbolic and salicylic acids, which are then eliminated by the kidneys, carbolic acid without being changed, salicylic acid after combining with sodium. Nenčki, Sahli, and Lepine have as a consequence recommended its internal use in "internal disinfection" in cholera, typhoid fever, and bacterial diseases.

Solubility of Medicines.

The act of solution, in which solid substances assume the fluid state through the agency of liquids, is one of the most important operations of practical pharmacy. The process has received a variety of names, according to the mode of applying the menstruum and the degree of heat employed; as maceration, infusion, digestion, decoction, displacement, or percolation and circulatory displacement.

Two classes of substances are the subject of solution; those which dissolve in the menstruum, as salts, gum, etc., and those which consist of soluble and insoluble matter, as roots, leaves, barks, etc. The former yield simple solutions; the latter infusions, decoctions, tinctures, wines, etc.†

It is our province here, to consider the subject in a different light, that is, the solubility of substances in their transition through the system as medicinal agents.

We know that the presence of acids, of alkalies, of albuminoid substances, and of fatty matter, is, if not indispensable, at least of use in aiding the solution and absorption of a large number of medicaments of themselves rather difficult of dissolution. It suffices to know this general law-the necessity of the presence of modifying substances-to understand that, according as they are in abundance, in small proportion, or not at all present, there will be facility or difficulty of absorption, or no absorp tion at all. Thus, the acid of the stomach will favor the introduction of all the substances which are in need of acid to penetrate into the economy; such as the metals and very insoluble acid salts. And thus again, the opposite condition will prevent absorption. Alkalinity of the intestines is favorable to the absorption of a certain number of substances, and, in particu

*Prof. A. Gubler.

†U. S. Dispensatory.

lar, of arsenious acid, as also of salts having an alkaline, or an earthy base, and which have acids rendering them insoluble. Thus, the tartrates and the oxalates of lime, of potash, and of soda, are little soluble when they are acid, and if they are easily soluble, then they are alkaline and basic; consequently, they can penetrate with more facility when the amount of alkali which they meet in the intestines is more considerable.*

There is within the intestines, with the exception of the cæcum, which is said to be acid, great scope to effect the solubility of medicines, owing to the alkalinity of the secretions. It is in those parts that a chemical reconstruction often takes place with many substances. Medicines that become soluble under the reaction of acids of the stomach, in reaching the intestines are precipitated, and then redissolved by the alkaline albuminous fluids of the intestines, and taken into the circulation. Not only resinates are thus dissolved, but metals; gold, silver, calomel, zinc, lead, sulphur, phosphorus and platinum. We have reason to think there are circumstances where substances pass through a triple and quadruple chemical change in their passage through the system, as affected by the acidity of the stomach, the alkalinity of the intestines, the albuminoids in the blood, and finally the acidity of the emunctories.

Albuminoid substances which are found in the intestines, and throughout the whole of the digestive duct, as well as in the blood, are not only emulsive agents, but perform the office of real solvents to facilitate the penetration of different substances into the circulation.* In the digestive duct they are able to dissolve calomel, which penetrates into the organism as an albuminate of protochloride of mercury, and behaves like calomel. This likewise applies to protoiodide of mercury, to sulphur, phosphorus, and to all substances that are soluble in mucus and albuminoid substances. It is said that calomel likewise may be dissolved in mucilaginous substances.†

It is a general law that albumen modifies remedial agents in a certain manner, to render their introduction into the economy more facile; but once introduced, this same albumen opposes in the blood the effects, whether chemical or physiological, which these remedies usually exercise on the organ with which they come in contact.*

Medicines Changed in the Blood,

and their Effects on the Blood. Some drugs have an immediate effect on the blood, either to impoverish it, or to improve it by oxidation. Mercury and the salines belong to the former; and nitrate, permanganate and chlorate of potassium, iron, etc., to the latter. The hemostatics, although directly intended for the blood, make no chemical impression on it, as is generally supposed-their power is in contracting the arterioles. Ergot fully reveals

*Prof. Adolph Gubler. † Personne.

this physiological action. So does turpentine through its stimulating properties, and its extraordinary penetrability, forcing its way through the protective albuminoids of the blood vessels, and acting as a direct stimulant to the capillary vessels, causing them to contract to resist its influence, and to keep it from invading routes not its own. The constitutional use of iron acts as an indirect hemostatic, so modifying the blood by oxidation that by its own normal force it will impart its tonicity to the blood vessels.

It is supposed by giving mercury, that it is found in the blood as a double albuminate.* and therefore contra-indicated in albuminuria and adynamic affections. It is evidently highly destructive to the fibrin of the blood.

Blood before the exhibition of nitre is cupped and buffed, but loses much of this character after its administration in quantity. It communicates a bright arterial tint to venous blood, and when added to fresh drawn blood it impedes coagulation. Why it fails as a hemostatic is evidently owing to the rapid elimination of the solids, under its diuretic effects.

Chloral coagulates blood as powerfully as is the effect of phenic acid. Therefore, when you introduce a solution of chloral, it must be a massive dose; because if over diluted it would produce a commotion of the heart. Thus you risk causing a coagulation of the blood, and giving rise to emboli to infarets and a suspension of life in some of the essential organs.

Chlorate of potassium, rich in oxygen, has without decomposition the valuable property by its mere presence to oxygenate or aerate the the blood, and so by restoring or exerting this vital character of the circulating fluid, influencing to a corresponding degree the nutrition and functional activity of the various tissues and organs of the body.||

There are substances which act while present in the blood, but they are gaseous or volatile bodies, which act in the same manner as the air in respiration, directly on the blood corpuscles, and which accomplish their destiny, it might be said, in the blood itself; these substances are hydrogen, carbonated (carburetted) hydrogen, carbonic acid and oxide of carbon, which spend their activity on the globules. The same is true of protoxide or binoxide of nitrogen-substances which act on the circulation, as do also nitrous and hypo-nitrous acid; and prussic acid, too. acts in the blood, as do the nitrites of amyl and of ethyl, and all the volatile and gaseous substances which induce anesthesia. These all induce phenomena which really pass into the blood, and no more striking proof of this is needed than their instantaneous and often fugacious action in the great proportion of cases.

In the human organism, and in the circulation, albumen will exercise its suspending prop: erties on substances introduced into the blood and circulating in the serum of that fluid; thus preventing the manifestation of a certain num