On the Mode in which Medicinal Agents Act when Introduced into the Stomach.

A legitimate, and by no means unimportant or uninteresting question, is, as to the mode by which medicinal substances act when introduced into the stomach, so as to remove abnormal states of the general system, or of particular organs. We will first look at their apparent effects, before examining the mode by which their action is effected.

Remedies may operate directly upon the organs diseased, and newly impress them,—change the morbid action present by substituting a new and different one that shall supersede or displace the primary affection; and by this means a cure is sometimes effected. Thus in dysentery, diarrhea, cholera morbus, nausea and vomiting, and many other disorders affecting specifically particular tissues, by exhibiting agents that exercise a specific influence upon the parts diseased, a new impression is produced corresponding with the morbid one already existing, though differing from it in kind and intensity of action, and by this means the original one is effectually removed. Indeed the substitution of a new action or impression in a diseased organ, often most effectually removes the primary one, and as soon as the part recovers from the temporary medicinal action, a normal state ensues. Although results of this kind do not always follow, yet the exceptions to this rule constitute no valid objection to the truth of the general proposition.

In this way cathartics prove beneficial in dysentery and diarrhea, emetics in cases of nausea and vomiting, and cantharides, turpentine, and other stimulating diuretics, in chronic irritation, or inflammation of the urinary organs. That other impressions and modes of action may follow the exhibition of these remedies, by which aid may be derived in subduing the morbid states, can not be doubted. Thus, they may excite the surfaces with which they come in contact to an increased secretion, and thus deplete the distended vessels, while the increased secretion may remove a noxious material from the blood, which has assisted to keep up the disease; the increased secretion may likewise shield, and thus lessen the irritability of the inflamed or irritated surfaces. The impression which they make upon other organs, or upon the general system, may also enable us to account in part for their sanative influences upon those tissues.

In the second place remedial agents may exercise a sympathetic influence upon the whole system. Some medicines act primarily upon the solids, and these impressions are transmitted through the agency of the nervous system to every part of the body. The remote effects of medicines are far from being confined to the parts with which they are brought into direct contact; on the contrary, parts distant from these are strongly influenced or impressed by remedial agents. Emetics, for instance, act primarily and specifically upon the stomach, but their most important sanative influence is transferred through nervous sympathy to other organs, and thus every tissue of the body is influenced or newly impressed by them; old associations and perverted sympathies are broken up, and a new action established, the tendency of which is, by this change of action and sensation, to restore the system to health.

The same remarks apply to cathartics. They act specifically upon the alimentary canal, causing alvine evacuations, and thus remove the vitiated and disease-creating accumulations of the intestinal canal—a prolific source of disease. But this is far from being the only way in which these contribute to the restoration of health. They excite the intestinal exhalents, and thus act as depletives, thereby promoting increased absorption and nutrition; they also exercise a strongly revulsive influence, by which a new surface or point of excitation is established, and by this counter-irritant effect, remote organs are relieved of congestion, inflammation and other morbid states. The whole system is impressed by their action, and important changes wrought upon the animal economy. Tonics and stimulants may act directly upon the sentient extremities of the nerves of the stomach, and thus arouse or excite that organ to increased energy, and thereby promote digestion; and thus favor the process of chymification and chylification, and by this means indirectly promote nutrition and the renovation of an exhausted or enfeebled system. By the agency of the same classes of medicines, a transmitted influence is extended through the nerves to every part of the body, and in this manner every fiber is newly impressed, and a modified state of the vital manifestations in every part of the body is the result.

In the same manner we may explain the therapeutic agency of other classes of agents in the removal of disease. In this way we may explain the highly sanative effects of ablutions— we apply them to the surface and the impression there made is transmitted to every portion of the system, and a general reaction results from a timely and appropriate resort to these means. The advantages attending their employment, often so conspicuous, can be explained only upon the ground that the new impression made upon the surface is transmitted by nervous sympathy to other parts of the body.

That the animal economy possesses the faculty of transmitting impressions, whether morbid or sanative, from one part to another is indisputable. This power is essential to the preservation of living beings, and the vital actions would soon cease, did not a connected medium exist, by which each part is brought into a reciprocal relation and mutual dependence upon others. The brain and nervous system constitute the medium through which these sympathetic phenomeua are transmitted, and remedial as well as morbid impressions are propagated through this source to all parte of the animal economy.

Thus every therapeutic agent or appliance may be said to alter or modify the sensations, actions, functions or condition of some organ through this medium; their primary action may be upon particular parts, and remote from those over which they exercise an important curative influence, and this secondary influence may not be in every case immediately appreciable. How wonderful then is the bond of union which exists between the various organs of our bodies; that it does exist, does not admit of a doubt; that a reciprocal intercourse of relations, sensations, and sympathies is maintained between all parts of the animal economy is apparent. These links unite all parts of the system, and thereby establish that concurrence of action, and that perfect harmony of function, which when beheld, can not fail to strike the observer with wonder and admiration. In this way then are we enabled to explain many of the sanative influences wrought upon diseased organs or states of the system by the administration of medicinal agents.

Again, remedies may act directly upon the blood, either adding something to it, or modifying its constituents. We have a large class of agents termed restoratives that act in this manner; they are of great importance in the treatment of any disease in which the blood mass has lost its normal character. In health, food is the proper restorative, it supplies the blood with all its constituents, with all substances required to supply growth, to repair waste, and to maintain the various functions at the healthy standard. Disease may result from improper food, or want of assimilation in that which is taken, and thus we have as the proximate cause a defect of some of the constituents of the blood. We have a familiar example of this in Chlorosis or Anaemia; in both these diseases there is a defect in the quantity of the red globules of the blood. The treatment in this case should be directed to the restoration of the defective material; this is done by the administration of iron, which assists to form the deficient element. Again we suppose that the class of tonics add to the blood some vital constituent that is lacking; no one can have failed to notice the beneficial effects of this class of remedies upon the system: all of them are readily absorbed, and chemists inform us that they are not excreted, without they are taken in large quantities. This being the case, it is reasonable to suppose that they remain in the blood, and assist in supplying material to the various parts of the body.

Some agents exert a modifying influence on the blood, and on the system; these agents are generally termed alteratives. This class of agents we know less about than any other; there is no doubt that many of them owe their medicinal action to their effect as diminutives, but their entire effect can not be ascribed to this cause, so that we must suppose a part of their action at least must depend upon their influence on the blood.

Again, some classes of agents owe their sanative influence to their eliminative action, either stimulating the excretory organs of the body to a normal performance of their function, or uniting with a morbid material in the blood, pass with it through an excretory organ, by virtue of their special affinity for it. To this class of agents belong cathartics, emetics, diaphoretics, diuretics, etc. They are used to remove morbid material from the circulating fluids. "To restore the natural secretion of a part when its diminution or stoppage results from torpor or deficient vascular activity of the secreting organ. To augment the natural secretion of a part, and thereby diminish the quantity of circulating fluid. To augment the natural secretion of a part, and thereby to promote absorption—as in dropsy. To augment the secretion of one part, and thereby to lessen the secretion of some other part. To augment the secretion of an organ, and thereby relieve local determinations of blood to remote parts; as when we administer purgatives to relieve determination of blood to the brain. To promote secretion, and thereby to favor the subsidence of diseases whose natural termination is by increased secretion. To produce exhaustion (the secondary effect of evacuants), and thereby to act as antipblogistics."

In the further consideration of this subject, we will adopt the propositions of Headland, with some modifications, as the basis of our remarks. Perhaps no other writer has done more to unravel the intricate questions in regard to the action of remedies than this author, and we will quote freely from his work where his views appear to be founded upon fact or correct reasoning. He bases his views of the action of remedies introduced into the stomach, upon ten propositions. These propositions relate to the general conduct of medicines after their introduction into the stomach, and before their absorption into the blood, and of their subsequent effects after they have passed into the blood. They are as follows:

Prop. 1. That the great majority of medicines must obtain entry into the blood, or internal fluids of the body, before their action can be manifested.

Prop. II. That the great majority of medicines are capable of solution in the gastric or intestinal secretions, and pass without material change, by a process of absorption, through the coats of the stomach and intestines, to enter the capillaries of the portal system of veins.

Prop. III. That those medicines which are completely insoluble in water and in the gastric and intestinal juices, can not gain entrance into the circulation.

Prop. IV. That some few remedial agents act locally on the mucous surfaces, either before absorption, or without being absorbed at all. That they are chiefly as follows:

a. Irritant emetics.

b. Stomach anaesthetics.

c. Irritant cathartics.

Prop. V. That the mcdiciue, when in the blood, must permeate the mass of the circulation, so far as may be required to reach the parts on which it tends to act. That there are two possible exceptions to this rule:

a. The production of sensation or pain at a distant point.

b. The production of muscular contraction at a distant point.

Prop. VI. That while in the blood the medicine may undergo changes, which in some cases may, in others may not affect its influence. That these changes may be:

a. Of combination.

b. Of re-construction.

c. Of decomposition.

Prop. VII. That a first class of medicines, called hematics, act while in the blood, which they influence. That their action is permanent.

1. That of these, some, called restoratives, act by supplying, or causing to be supplied, a material wanting, and may remain in the blood.

2. That others, called catalytics, act so as to counteract a morbid material or process, and must pass out of the body.

Prop. VIII. That a second class of medicines, called neurotics, act by passing from the blood to the nerves, or nerve-centers, which they influence. That they are transitory in action.

1. That of these, some, called stimulants, act so as to exalt nervous force, in general or in particular.

2. That others, called narcotics, act so as first to exalt nervous force, and then to depress it, and have also a special influence on the intellectual part of the brain.

3. That others, again, called sedatives, act so as to depress nervous force, in general or in particular.

Prop. IX. That a third class of medicines, called astringents, act by passing from the blood to muscular fiber, which they excite to contraction.

Prop. X. That a fourth class of medicines, called diminutives, act by passing out of the blood through the glands, which they excite to the performance of their functions.

The first proposition affirms that the great majority of medicines must enter the blood before they can exert their peculiar influences upon the system. That this is true is readily proven by the fact that medicinal agents introduced into the stomach disappear, and no trace of them can be found in the alvine evacuations, unless they are agents which act specifically upon the alimentary canal. It is proven by the action of remedial agents upon the child at the breast, showing that the remedy has been absorbed, and that the milk of the mother has been medicated, it being rendered purgative by senna and narcotic by opium. Rhubarb in the secretions, madder in the bones, silver in the skin, and mercury in various parts of the body, when these agents have been administered, are additional examples going to prove the same proposition. Again, the odor of musk, garlic, onions, and various other agents, is readily detected in the cutaneous excretions, and in the breath. The coloring matter of indigo, iodine and madder is recognized in the milk, and the same principles, as well as the chemical constituents of agents almost without number are readily detected in the urine.

It is said that the amanita muscaria, a species of fungus, produces inebriation, and that the inhabitants of Northern Asia use it for this property. He who has eaten it will, in the course of twenty-four hours, have slept himself sober; when if he takes a teacupful of his urine, he will again become intoxicated; and a party of drunkards, it is said, may keep up their debauch for an indefinite period of time by drinking the urine of each other—one only having eaten the fungus.

That medicines act after having gained entrance to the blood, and that this is requisite to their action, is proven by the fact that remedies act in the same way when introduced into any other part of the system, or by being injected into the veins, as they do when introduced into the stomach. Thus iodine injected into the scrotum, for the cure of hydrocele, has been detected in the urine. Croton oil, or a liquid preparation of gamboge, jalap, or rhubarb, rubbed in sufficient quantity upon the abdomen, produces purging. A moistened leaf of tobacco applied over the radial artery, has been known to produce vomiting. A solution of aconitina applied to the skin, will produce numbness and tingling of distant parts. When medicinal substances are injected under the skin, they produce the same effect as when introduced into the stomach: thus, emetic substances produce vomiting; castor-oil, purging; opium, or its active principles, narcosis; strychnine, convulsions, etc.

It is proved that remedies must act through the blood, and not through the medium of the nerves, by the direct experiment that a poison will not act when introduced into the body, if the circulation from the part is cut off. Or the reverse experiment of Magendie proves this position. He introduced into the crural artery of a dog, the barrel of a small quill, upon which he fixed the vessel by two ligatures; the artery was divided in a circular direction between the two; he then did the same with the crural vein; thus all communication between the thigh and the rest of the body was interrupted, except the arterial blood, which passed to the thigh, and the venous blood, which returned from it. The poison introduced into the part produced its effect in the ordinary time—about four minutes. In this instance there could be no doubt but that the poison was absorbed by the veins, and through them carried into the circulation, from which it acted.

The objection that some agents act so rapidly that there is not sufficient time for their absorption and conveyance in the circulating fluids to the part on which they act, is also removed by direct experiment. Mr. Blake made an experiment on a dog in order to test the rapidity of absorption: he placed half a drachm of hydrocyanic acid on the tongue of the animal, having first fitted a tube into the larynx, so as to prevent the vapor from passing into the lungs; he found that fifteen seconds elapsed before any morbid symptoms appeared, and death did not occur until forty-five seconds after the exhibition of the poison. Mr. Blake also found that a chemical agent would traverse the entire circulation of a dog in nine seconds, and of a horse in twenty seconds; so that sufficient time elapses for the absorption and conveyance through the system of even those agents that act with the greatest rapidity.

The second proposition states that the great majority of medicines are capable of solution in the gastric or intestinal secretions, and pass without material change, by absorption, into the capillary veins of the stomach and intestines. That they do this is proved by the facts already stated, but the question is, how is it accomplished? The physical agency by which absorption is accomplished (imbibition of Magendie, or endosmosis of Dutrochet), consists in the tendency of rarer fluids to permeate membranes into cavities containing those of greater density. The circumstances which determine the passage of fluid through the coats of a vessel are principally five: 1. The densities of the liquids.—Other things being equal, the lighter of the two tends to pass through to the heavier, more than the heavier to the lighter. 2. Their attraction for the intervening membranes.—That one passes through most, which has the greatest affinity for the membrane. 3. The affinity of the fluids for each other.—A fluid passes through more rapidly when it is readily taken up and dissolved by that on the opposite side. 4. The motion of the fluid on one side promotes the passage through of that on the other, because it is carried off as fast as it permeates the membrane. 5. The last law is that any pressure on the fluid on one side of the membrane has a powerful influence in determining the passage of the current from that side.

Magendie demonstrated the fact that when there was vascular repletion, absorption was very slow; but by depleting the vessels, absorption became very active. In one instance he injected about a pint of water into the veins of a dog; and placing in the pleura a moderate dose of a substance with the action of which he was familiar, he found that its effects were not apparent until many minutes after the ordinary time. In another experiment he depleted the vessels by abstracting a half-pound of blood, and the effects which ordinarily did not occur until the end of two minutes, developed themselves in thirty seconds.

Remedies, however, can not be absorbed without they are first dissolved and held in solution. A large number of agents are soluble in water, and these are readily absorbed. Some are rendered soluble by the addition of an acid to the water, and as the gastric juice contains an acid we have here the materials for their solution. Again others require a fluid with an alkaline reaction; and passing down into the duodenum they come in contact With the bile, an alkaline fluid, and are thus rendered soluble. Albumen and like matters are rendered soluble by the action of the gastric juice. Thus a great majority of remedies are rendered soluble, and are then absorbed; but we have agents that are insoluble in any of these fluids, and these either pass through the alimentary canal without exerting any medicinal influence, or they act as irritants or sedatives to it.

The third proposition affirms that those substances that are insoluble can not be absorbed into the circulation. This is a generally admitted fact and needs no proof, as its affirmation would conflict with well-known physical laws.

The fourth proposition affirms that some remedies act locally on the parts with which they come in contact. Some of these agents act first upon the stomach and intestines and are then absorbed; others are entirely insoluble and after their action pass from the body with the feces. These agents may be classed as follows: 1. Antacids, 2. Chemical Antidotes, 3. Astringents, 4. Anaesthetics, 5. Irritant Emetics, 6. Irritant Cathartics, 7. Agents which affect the process of Endosmose.

1. Antacids are employed to neutralize acidity of the stomach; they combine with and neutralize free acids contained in this viscus; they are then absorbed. Pereira states that they probably aid in the digestion and absorption of fatty substances, especially when there is a deficiency of bile and pancreatic juice.

2. Chemical Antidotes are used to counteract poisons by rendering them insoluble, or converting them into harmless substances.

3. Astringents exert their effect locally as styptics, checking hemorrhage from the stomach.

4. Anaesthetics are employed to relieve gastrodynia and other painful diseases of the stomach. They include hydrocyanic acid, creosote and tris-nitrate of bismuth, and probably some others. They act in the same manner as aconite or morphia in painful diseases of the skin, by paralyzing the sentient nerves of the stomach — this action depending on local contact. The first two are afterward absorbed; but the third is insoluble, and acts also as an astringent to the mucous surface.

5. Irritant Emetics act by producing local irritation of the mucous membrane of the stomach. The impression is transmitted to the spinal cord, and by a reflex action the muscles concerned in the act of vomiting are excited to action, to expel the offending substances. Such agents produce but little nausea, and unlike specific emetics, which act upon the stomach into whatever part of the system they are introduced, these act only when brought into direct contact with the mucous membrane of the stomach.

6. Irritant Cathartics act in a similar manner as the same class of emetics; that is by their irritant effects on the mucous membrane of the intestinal canal, they cause an increased secretion from that canal, and stimulate the peristaltic action. Their action differs widely from that of specific cathartics; for these latter, as castor-oil, aloes, rhubarb, colocynth, elaterium and others will act as cathartics if absorbed through the skin, or injected into the veins. Many agents act in both ways, that is, they are partially absorbed and exert their influence through the blood; but being slowly soluble in the fluids of the body they exert a direct, irritant effect upon the walls of the intestine. We have examples of this in the class of resinous cathartics — as scammony, gamboge, euphorbium, podophyllin, etc. These agents are sometimes of great value in disease of distant parts of the system, by their revulsive or counter-irritant effect.

7. Some agents effect the process of Endosmose—they may increase the absorption of other agents, or they may cause an endosmose of the blood serum into the stomach and intestine, or they may entirely check the process of endosmosis. Pereira makes the following classification:

"1. Substances which undergo Endosmose and Exosmose with the Serum ofthe Blood.—The kind of endosmotic influence which these bodies exercise varies, in many cases, with the degree of concentration of the solution. Very concentrated solutions in general cause endosmose of the serum; whereas dilute solutions bave a reverse effect, and give rise to endosmose of the solution; and for solutions of an intermediate strength, the two currents are equal.

"a. Substances which cause Endosmose of the Serum.—This division includes concentrated solutions of various salts (phosphate of soda, nitrate of potash, chloride of sodium, iodide of potassium, tartrate of potash, sulphates of soda and potash, phosphate of potash and alum), native Seidlitz water, Pultna-water, sufficiently concentrated solutions of certain vegetable purgatives (manna and the extracts of senna, rhubarb, the herb mercury, tamarinds, cassia, colocynth and aloes, resins of scammony and jalap, and castor-oil), of various narcotic substances (one part of the alcoholic extract of the following substances to five parts of water: black hellebore, hemlock, henbane, aconite and belladonna), solution of cane sugar (this causes a very powerful current), dilute spirit, and a solution of cantharidin in olive-oil.

"b. Substances which cause Endosmosis of the Solution.—This division includes water (which produces the strongest current), dilute solutions of salts (phosphate of soda, nitrate of potash, chloride of sodium, and iodide of potassium), solutions of certain acids (acetic, tartaric, citric and sulphuric acids), of ammonia, of nitrate of strychnia, and of sulphate of quinia, hydrocyanic acid, laurel water, and certain non-purgative mineral waters.

"2. Substances which do not undergo Endosmose and Exosmose with the Serum of the Blood.—These may be arranged in two divisions:

"a. Substances which penetrate the Membrane and render it unfit for Endosmose.—To this division belong the solution of sulphureted hydrogen and decoction of tobacco. Under the influence of either of these liquids, the membrane becomes permeable, and yields to that liquid which exercises the greatest amount of pressure.

"b. Substances whose presence puts a stop to the Phenomena of Endosmose, and renders the Membrane impermeable to either Liquid.—To this division belongs the solution of hydrochlorate of morphia."

According to the generally received opinion of the laws of endosmosis, the purgative salts are purgative only because they are of greater density than the blood, and therefore cause an endosmose of the serum of the blood to the intestine, the increased distension exciting the peristaltic action of the bowels; hence these agents are generally hydragogue cathartics. This action is according to the law of endosmosis, that a fluid of great density, when separated by a membrane from one of less specific gravity, will cause an endosmosis of the lighter fluid.

This theory of the action of saline purgatives is adopted by Poiseble, Liebig, Matteuci, Dr. Pereira, and Dr. Golding Bird. They also contend that when these salts are much diluted they become diuretics and are excreted by the kidneys. On this point Dr. Bird states "that when saline substances, especially, are intended to reach the kidneys, it is necessary that the density of their solutions should be much below 1.028; the proportion of solids dissolved in the aqueous vehicles prescribed being always less than five per cent. Daily experience in the employment of remedies will show the importance of this law in a therapeutic sense. Thus a tolerably strong solution of the tartrate, or the acetate of potass, will altogether escape the action of the absorbents; indeed, so far from being imbibed by the capillaries, it will actually excite an exudation of water from these vessels into the stomach and small intestines, thus becoming diluted by exosmosis, a sensation of thirst is excited, by which the patient is compelled to drink for the purpose of supplying the water removed from the blood by exudation. In strong solutions, the salts alluded to stimulate the bowels and purge. They are moreover said to act as hydragogue purgatives, producing watery motions, a fact capable of ready explanation on physical laws; exudation of water from the exhalents (capillaries) occurring on account of the density of the saline solutions traversing the intestines. We can hence readily perceive why half an ounce of acetate or tartrate of potass will purge, and a scruple of either excite diuresis."

The fifth proposition states that medicines after they gain access to the blood, must permeate the mass of the circulation so far as to gain access to the parts on which they tend to act. This is proven by the fact that the agents may be detected in the different parts of the body, and in the secretions and excretions. We suppose that remedies have a special affinity for the parts on which they tend to act. As to the reason why particular agents act upon particular organs instead of others it is idle for us to speculate. Why do certain agents seek out and act upon the kidneys instead of other organs, and why do cathartics exert a specific influence upon the intestines, even though introduced into the blood vessels, or into some of the cavities of the body, or absorbed through the skin, and not taken into the alimentary canal? The reason we can no more explain than we can the reason why the planets are kept revolving in their orbits. If we are told that the movements of the planets are the result of attraction, so we may say that the determination of medicines to certain organs is occasioned by similar attractions. This, however, explains nothing, and we must, after all, be content with the broad fact that such phenomena do occur, and that they are governed by certain laws; but the cause why they occur must forever remain concealed. As readily could we explain the reason why one plant possessing the most deadly poisonous qualities, and another that is not only innocuous, but delicious, and highly nutritious, should be produced from the same soil, both being placed in the same conditions.

The sixth proposition states that while in the blood, medicines may undergo changes, which sometimes affect the action of the agent, and at others do not. This proposition is too circumscribed for practical purposes; for instance, we administer a dose of some agent, we wish to know first, whether it is changed before being absorbed, as we know this does take place in some instances, and whether this change affects the action of the remedy or not; then we wish to know what changes, if any, take place while the agent is in the blood. We will first consider the changes that take place in the stomach.

According to Pereira, "Some substances undergo no obvious chemical change, but being liquid or soluble, mechanically mix with the fluids of the part to which they are applied and become absorbed, as venous aqueous liquids, holding in solution coloring, odorous and other matters."

Some substances undergo more or less chemical change by the action of acids, bases, salts, albumen, casein, ptyalin, pepsin, or other substances with which they come in contact; and the newly formed body is, if soluble, absorbed but not otherwise.

The alkaline and earthy carbonates are decomposed by the acids of the alimentary canal, with the evolution of carbonic acid.

Most of the metallic oxides, and the metallic, alkaline and earthy salts, form new compounds with albumen, casein, etc.

Chalybeate preparations, when swallowed, are partly converted into sulphuret of iron, which darkens the feces.

The acith, both inorganic and organic, combine with bases; and the salts which are thereby formed unite with organic matters.

After being absorbed, medicinal agents may be changed in their combination ; they may be reconstructed or decomposed. Our knowledge, however, of these processes in the blood is not sufficient to elucidate any facts which would have any bearing on the action of remedies; neither can we tell whether an agent has been chemically changed in the blood, or in the stomach, or the excretions. We do know, however, that very few changes take place in the blood which affect the action of the remedy.

The seventh proposition maintains that a certain class of medicines, called hematics, act while in the blood, which they influence; and that their action is permanent. These agents are supposed either to add a material to the blood which was deficient, or to remove a material from the blood which was unnatural to it, or in some way change its character.

The first of these classes, called restoratives, embraces the most important agents of the materia medica; as already stated, they add to the normal constituents of the blood, and thus form a portion of the circulating fluid. They must then be such agents as would assist to form this fluid in a healthy state of the system, i. e., the blood must normally contain their analogues. It must not be supposed, however, that these agents are restorative in all conditions of the system, for the constituent of the blood which they increase may be in excess; hence a large number of them only prove restorative in certain forms of disease.

Headland lays down the following minor propositions in regard to their action:

"1. That they act in the blood, and that their effects are permanent.

"2. That there are naturally in the blood substances which resemble or coincide with them.

"3. That they are of use when a disease depends on the want of one or more materials in the blood."

The following classes of agents may be called restoratives in this sense: Tonics, chalybeates, acids, and alkalies.

The first class or tonics act first by increasing the tone of the stomach and entire alimentary canal; thus stimulating (though the effect is permanent) the process of digestion and assimilation, thus improving indirectly the quantity and quality of the blood. Do they do this merely by contact, acting locally, or are they first absorbed, then acting from the circulation? The bitter principles of agents of this class are almost invariably alkaloids, readily soluble in water, or in the gastric juice, and hence quickly absorbed, so that the contact of these agents with the surfaces of the alimentary canal is but of very short duration, and extends generally to only a portion of the stomach: this would tend to prove that they acted after being absorbed. By this stimulation of the digestive process we might account for the entire medicinal action of this class of remedies, as by this means they increase the quantity and quality of the blood, and the nutrition of the system; but we have reason to believe they do more than this. In miasmatic diseases, and fevers caused by the retention of an excretion, they are very efficient in counteracting the septic tendency of the morbid material. Is this action not owing to their counteracting the chemical changes going on in the body, in a similar manner to the action of hops in checking the fermentation of malt in the manufacture of beer?

In regard to the action of cinchona, which may be taken as the type of this class of agents, Sundelin observes: "The general operation consists in the increase and exaltation of the tone of the irritable fibers of the vessels; hence, by its use the pulse becomes fuller, stronger and regular, and the muscular power increased; also in the general augmentation of the cohesion of the organic mass; hence, it counteracts a tendency to liquefaction and disintegration, diminishes profuse secretions, which proceed from atony of the extremities of the vessels, and of the secerning surfaces and organs, and improves generally the crasis; and lastly, in the augmentation of the vital energy of the sensible system. By the last-mentioned property it restores sensibility, when defective or abnormally increased, and the property of reaction of the nervous system to their nornial state, and augments the influence of this system on the muscular fiber, and on the reproductive system."

The different compounds of iron, or chalybeate remedies, act by directly supplying a material to the blood. They appear to be of benefit in but one condition of the system, that of anemia; and this disease or condition depends upon a deficiency of the red globules of the blood. The coloring matter of the red globules or hematosin, contains this mineral, and without a due supply of it the red globules can not be formed. Thus, by the administration of iron, the solid constituents of the blood in a case reported by M. Simon, had increased from 128.5 to 198.5 in 1,000 parts. The first effect of the iron is probably upon the red globules; it restores the deficient material, thus improving their condition, and by this means stimulates the entire system to a proper performance of its functions.

Acids prove indirectly restorative in some cases by increasing the amount of the acid in the gastric juice, as in cases of weak digestion depending upon deficient secretion of this acid. It may increase the acid of the gastric juice either directly or indirectly; it increases it directly by being added to it, indirectly by being absorbed into the blood where it would set free more of the acid than the stomach is required to furnish. If, however, there is too much acid secreted, these agents will cause indigestion; the same result will follow their inordinate use.

It is stated by Pereira that acids always combine with bases before absorption. Other authors suppose that they are absorbed as free acid; in either way, the alkaline base is derived from the blood, and hence they decrease the alkalinity of this fluid. The blood always has an alkaline reaction; hence there is rarely, if ever, a free acid in it. The beneficial effects of the vegetable and mineral acids in typhoid and other low forms of fevers, has been supposed by some authors to be owing to their neutralizing the excess of alkali, which existed in the blood in those diseases.

According to Headland, the beneficial effects of vegetable, acidulous drinks in febrile diseases, seems to be the restoration of the blood to a more natural condition, by supplying a material for oxydation. He says: "In fact, I suppose that in fevers the supply of the natural blood fuel is deficient; that the nitrogenous tissues are then oxydized to maintain the animal heat—causing not only wasting, but tending to keep up the fever by the excessive amount of oxygen demanded by this abnormal combustion; that in such a case the vegetable acid is well adapted to take the place of lactic acid, the natural fuel. For though in health the ingestion of such an acid is immediately followed by an increased acidity of the urine, when used in fevers it does not pass into the urine. It is then disposed of, or burnt, in the blood. The alkaline salt of the same acid is similarly burnt, as it would be in health; but it leaves a residue, an alkaline carbonate, which exerts upon the system the usual operation of an alkali."

Again, the mineral acids have been strongly recommended in phosphatic deposits from the urine; they are supposed to increase the acidity of the urine, and by this means the phosphatic salt is held in solution. On this subject Dr. Golding Bird says: "Unfortunately there is a great uncertainty attending their use; indeed, I feel almost inclined to question whether any of the mineral acids, except the phosphoric, really do reach the urine, and thus destroy its alkaline character; certainly in the majority of cases, even their continued employment appears to be utterly ineffectual in rendering the urine acid."

Alkaline agents prove restorative in those cases where there is a deficiency of these agents in the system, or an excess of acid; in the former case they supply the deficient material, and remain in the blood; in the latter they neutralize the excess of acid, forming salts, and are excreted from the system. They are also used to counteract the lithic acid deposit. They are supposed to be useful in rheumatism by neutralizing the acidity of the blood and the secretions.

The second class of hematic medicines, according to the proposition we are now considering, are called catalytics (from καταλυω, to loosen, break up, dissolve), from their supposed action in destroying or counteracting certain morbid agencies. The term employed to designate this class of remedies is certainly no more appropriate than the one formerly used—the agents included under this head forming the old class of alteratives. The action of this class of remedies is so obscure that we will defer what we have to say upon them till we come to consider alteratives as a special class.

The consideration of the eighth, ninth and tenth propositions may well be deferred until we treat of the classes specified in them. The propositions themselves state all we know of their mode of action.

The American Eclectic Materia Medica and Therapeutics, 1898, was written by John M. Scudder, M.D.