CHAPTER III.

ON THE GENERAL MODES OF ACTION OF THERAPEUTIC AGENTS INTRODUCED INTO THE STOMACH.

The principal affirmations which I have to make on this subject are divisible into Ten Propositions, as seen in the Table of Contents.

The first four of these concern the general conduct of medicines after their introduction into the stomach, and before their passage into the blood. Some broad rules are laid down by which the course which they take must be determined. The action of some few on the mucous membrane is also defined.

The remaining six propositions treat of the subsequent behaviour of those medicines which pass into the blood and fluids of the body. Of these, the fifth specifies their general course. The sixth states that they may undergo certain changes in the system. And the concluding four treat of the various modes in which these agents may operate in the cure of disease.

The first proposition lays down the great fundamental rule of the action of medicines through the medium of the blood and fluids.

PROP. I.--_That the great majority of medicines must obtain entry into the blood, or internal fluids of the body, before their action can be manifested._

This is to say, that the mere contact of a medicine with the stomach is not in general sufficient for the production of its peculiar action. It will be seen that the only apparent exception to this rule consists of agents having a mere local action on the mucous membrane, for which simple contact is all that is required.

Even when acting on any part of the system removed from this mucous surface, as when applied to the skin, it is necessary that the medicine pass away from it to enter the blood or internal fluids. In the great majority of instances it enters the blood directly. But we know that it would be sufficient for its operation if it were to enter through the chyle, or into the serous fluid which exists in the interstices of the tissues throughout the body. For by these it might at length be conducted to distant parts. This is what is meant by _internal fluids_.

We are not just now concerned with the way in which this passage into the blood and fluids is obtained. It is by the process of absorption. The question of passage by absorption is treated in the second and third propositions. What we have now to decide is, whether a medicine acts by mere contact with the stomach, its influence being propagated to distant parts by means of the nerves; or by passage thence into the system, acting through the medium of the blood and fluids. I affirm that it operates in this latter way; and this is to be proved by four considerations, which we will consider in succession.

_A medicine introduced into the system elsewhere acts in the same way as when introduced into the stomach._

This proves at least that contact with the mucous surface is not an essential requisite for the operation of a remedy. We may cause a medicine to be absorbed by the skin, or inject it directly into an opened vein. The result of this latter experiment proves not only that entry into a distant part of the system is sufficient for the action of a medicine, but that it will operate when introduced into the blood. Numberless proofs of this affirmation may be adduced. Tartar Emetic injected into the veins produces vomiting. Croton Oil rubbed on the surface of the abdomen causes purging. Mercurial ointment applied by friction to the skin will produce salivation. Extract of Belladonna applied to the temples causes dilatation of the pupil of the eye; and tincture of Opium dropped on the eyeball causes the pupil to contract. Ammonia inhaled as gas into the lungs will relieve fainting in the same way as when swallowed. The breathing of Prussic acid, causing its vapour to be applied to the pulmonary surface, is sufficient to kill. Prussic acid, dropped in a concentrated state into the eye of a dog, causes speedy death. Solution of Aconitina, applied to the skin, will produce numbness, and tingling of distant parts. Injection of Nux Vomica, or any powerful poison, into the veins, is rapidly followed by symptoms of poisoning, like those which would have followed its introduction into the stomach.[17] Thus contact with the stomach is not necessary, but introduction into the system any where is sufficient. But still, may not the poison in either case act by influencing the nerves? Even when it has entered the blood, it may not travel along in it, but act in a more direct way. So in the second part of the proof we must show that a remedy cannot act by an impression conducted from the surface of the stomach by means of the nerves.

_The continuity of nerve is not necessary for the propagation of such effects; but vascular connexion is necessary._

This alone, if established, would be sufficient to prove that a medicine must be introduced into the circulation, in order to act on distant parts. When confined to a surface, it can operate on the remote part only by its contact with the superficial extremities of the nerves. For vascular connexion to be established, it must first enter the vessels. Many experiments have been made which demonstrate that the vessels are the only channel by which medicinal effects can be propagated.

M. Magendie introduced some Woorara poison into the limb of a dog, which was only connected with the trunk by means of quills uniting the divided ends of the main vessels. It rapidly took effect. Having divided all the nerves and lymphatics in the intestine of another dog, he introduced into it some Nux Vomica, beyond the division. It quickly acted, and must again have done so through the vessels. Sir B. Brodie cut all the nerves of the anterior extremity of a rabbit, near the axilla, and then introduced Woorara into the foot. It rapidly acted.[18] Thus we see that vascular connexion is sufficient, and that nervous connexion is not necessary. By other similar trials it is found that vascular connexion is absolutely necessary, for when it is interrupted, the action cannot be propagated along a nerve. If, on introducing poison into an extremity, a cord be tightened round the limb above it so as to intercept the flow of blood, no effect is produced. It takes effect after the ligature is relaxed. Sir B. Brodie introduced Woorara into the leg of a dog, which was connected with the trunk only by means of the principal nerve, carefully dissected out. No effect followed. M. Ehbert found that poison would not act when applied to an amputated limb connected with the trunk by a nerve only. Thus vascular connexion is necessary; whereas continuity of nerve is not necessary, neither is it sufficient by itself.[19] Woorara poison is a substance which acts with great rapidity on the nervous system; and if its action cannot be propagated by means of the nerves, _à fortiori_ would it seem that slower poisons must act through the circulation. But, granting that it has been shown that introduction into the stomach is not necessary for the action of a medicine, and that when in the stomach medicines do not act by influencing the nerves, still it may be objected that the rule cannot possibly be universal. It may be urged that some poisons and medicines, as Hydrocyanic acid and Ammonia, act with such great rapidity, that we can only suppose their influence to be transmitted directly along a nerve-fibre to the nervous centre, because the process of passage in the blood to this distant part would be far too slow. This argument requires us to prove a third thing.

_The circulation of the blood is sufficiently quick to account even for the operation of those poisons which act most rapidly by influencing the nerve-centres._

There is no poison whatever which acts so quickly on distant parts that the circulation cannot previously have had time to conduct it to them. By means of an instrument invented by M. Poisseuille, Dr. Blake found that a chemical substance traversed the whole circulation of a dog in nine seconds, and of a horse in twenty seconds.[20] The results of Hering were similar. M. Volkmann, in the tenth chapter of his work on Hæmadynamics, states, as the result of several experiments, that the whole circulation in an adult man occupies exactly 65.76 seconds.

Now a poison that operated by nervous connexion would probably operate directly when it touched the stomach. This is not the case even with Hydrocyanic acid. This, the most sudden of all poisons, before it takes effect, allows sufficient time to elapse for the blood to conduct it to the brain. Blake made an interesting experiment upon it. He placed some on the tongue of a dog, having first fitted a tube into the larynx, so as to prevent the vapour from passing into the lungs. The effect did not commence until sixteen seconds had elapsed, and forty-five were required for its completion. This allowed of time for absorption.

Thus it is proved that poisons act when introduced into the system at any point; that vascular connexion is required for this action; and that the rapidity of the circulation is in all cases quick enough to account for it.

But this last is only a proof of _possibility_, and does not by itself show that a substance may not nevertheless act through the nerves. And to the experiments on nervous connexion some may object that no conclusions on this point can be drawn from trials made on isolated and exposed nerves. So we may imagine a person to be still incredulous as to the truth of the Proposition, that medicines must pass into the blood before they can act. But a fourth consideration will suffice to bring this probability as close as possible to a certainty.

_The great majority of medicines have been detected in the blood, and found in the secretions formed out of it._

Having tried to prove that they must pass into the blood, if we find that they actually do so, we shall establish a stronger case. Isolated observations on this subject have been frequently made. Thus in 1847 Mr. Allen detected Daturia in the urine of a man poisoned by Stramonium. In 1824 M. Runge had discovered in the same way the principles of Henbane and Belladonna. M. Ragsky has lately detected Chloroform in the blood. (_Journal für Prakt. Chem. 1849._) Dr. Golding Bird observes that Indigo, when given for Epilepsy, has turned the urine blue; that Logwood also passes into it, and causes it to give a dark precipitate with solutions containing iron; and that during a course of Copaiba or Cubebs, a resin may be precipitated from it on the addition of Nitric Acid. If a medicine cannot be proved to pass into the blood or secretions, we cannot so certainly affirm that it does not act through the nerves. But the experiments of Tiedemann and Gmelin, and since then of Wöhler, have definitively settled this point. The former two have found the great majority of mineral, and many vegetable substances, in the blood of animals to which they had been administered.

Thus, from these four considerations, we are strictly justified in concluding that a medicine must pass from the stomach into the blood before its action can be manifested. This action cannot then be conducted from the surface of the stomach through the agency of the nerves. Some experiments made by Dr. Garrod and others on the action of animal charcoal as an antidote, furnish again an additional confirmation of this fact. He finds that if a sufficient quantity of this absorbing agent be introduced into the stomach before time has been allowed for the passage of a medicine through the mucous membrane, then even such powerful nerve-medicines as Morphia and Strychnia, in very large doses, are prevented from taking effect. Yet before the contact of the charcoal they would have had time to act through the nerves, had they been capable of any such action.

In the fifth Proposition the rule here laid down will have to be further extended. It will be shown that medicines, having already passed into the blood, must travel along in it so far as to reach the part of the system on which they act.

Before concluding this question, a few remarks must be made on a subject which will be again referred to in the discussion of the Fourth Proposition.

The proper and peculiar action of a medicine, by which I mean that action on the system which is immediately recognised as distinct from that of any other agent, cannot be exerted on distant parts from the stomach-surface, but requires the passage of the medicine into the circulation. But can any other action on distant parts be produced by the remedy while in the stomach? This is a different question, and must be answered in the affirmative. Suppose a Cantharides plaster be applied to the surface of the chest in a case of Pericarditis, so as to redden or blister the skin, absorption of the fluid in the pericardium may follow this application. But any other irritant would have done this. It is not the proper or peculiar action of Cantharides, but an operation of the nervous system which follows the local change. Such agents are said to act by _Counter-irritation_ or _Revulsion_, because it appears that, as a consequence of their action, the attention of the nervous system may be drawn off from a morbid process going on at some other part of the body. But it is only a consequence, and not a direct operation. Such an effect is no more the action of Cantharides than the healthy functions following recovery from sickness can be ascribed to the remedy which has cured the latter.

Now some few medicines have a marked local action on the mucous surface of the stomach and intestines. (_Vide_ Prop. IV.) These, and these only, may, without passing into the blood, produce on distant parts an action of this kind by counter-irritation. Thus the operation of an irritant emetic may be followed by the arrest of some incipient inflammation, _e.g._ Ophthalmia. This revulsive action, when carried to an extreme, so powerfully impresses the nervous system, that it puts a stop to all other actions, and produces Syncope or Death. This extreme action is called _Shock_. Powerful corrosive poisons may effect this by a sudden destruction of the mucous surface, operating like a surgical injury. But such actions, not being the proper and characteristic operations of medicines, but rather attributable to a change in the relations of the nervous system, following a local impression, are not to be considered as exceptions to the above rule, that medicines cannot from the surface of the stomach or intestines propagate their influence to remote parts.

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._

It has already been shown of medicines in general, that it is necessary for them to pass away from the mucous surface into the circulation. Mention has been made of their discovery in the blood by chemical means; and as we proceed it will be shown more particularly of different sets of medicines that each of them has been found in that fluid. Now, to gain entrance there, the medicine must first pass through the soft mucous membrane lining the stomach and intestine. This passage is performed by a process to which the names of _Absorption_ and _Endosmosis_ have been applied. Immediately outside this membrane, and between the tubes and cells which are formed by its involution, is a close net-work of very small veins, having thin and delicate walls. Now the same forces, whatever they be, which conduct the medicinal solution through the mucous membrane, cause it to pass on through the fine walls of these vessels. The two membranes, lying in such juxtaposition, are to all intents the same as one. Thus the medicine passes into the blood, and this is the only direct way by which it can gain entrance into it. These small veins, or capillaries, lead at length to the Mesenteric veins, which pour into the Portal vein, by which the blood proceeding from them is conducted into the Liver. The process of Absorption is the only mode by which remedies can thus enter the blood; we have now to consider what it is, and to show in what manner and by what agents different medicines are fitted to undergo it.

The subject of this Proposition divides itself naturally into three parts. We shall have to consider--1. What is the nature, and what the function, of the gastric and intestinal secretions. 2. The laws of this process of Endosmotic absorption, and how they are fulfilled in this case; and, 3. The mode in which the great majority of medicines are reduced to a state of solution, which is necessary before they can be absorbed.

The process of stomach-digestion has been cleared up of late years by the decisive experiments of Spallanzani and Réaumur, of Tiedemann and Gmelin, and of Dr. Beaumont of Canada.

Immediately that a substance touches the mucous surface of the stomach it causes the copious outpouring of a thin fluid, which is secreted by a glandular apparatus. This gastric juice is highly acid, and contains besides a peculiar nitrogenous substance called Pepsin. Dr. Prout thought that the reaction was due to free Hydrochloric acid. But it seems more likely that it is due to Lactic acid. Such at least is the opinion entertained both by Liebig and Lehmann. Now the result of the action of this fluid is to dissolve down the solid materials of the food, or other substances presented to it, reducing them to a thin watery pulp. This pulp is then mainly absorbed; and that which is not taken up through the coat of the stomach is absorbed in the earlier portion of the intestinal canal. I shall have to treat of Aliments as one of the orders of Restorative Hæmatics.

We are now concerned with medicines in general. The same juice is poured out to receive them. Such as are dissolved by it are immediately absorbed. Some other matters may be rendered soluble by the agency of the Bile and Pancreatic juice which are poured out into the middle of the Duodenum. The former is an alkaline fluid, containing carbonate of Soda. The Pancreatic juice is also said to be alkaline. That the stomach is absorbent may be proved by the experiment of placing a ligature round the intestine of a dog, just below the pylorus. It is then found that soluble substances placed in the stomach pass rapidly from it into the circulation. It is probable that all substances which are easily dissolved pass through the coats of the stomach. That the surface of the intestines is absorbent may be proved by the disappearance of enemata thrown into them. Liebig states that a solution of common salt, in the proportion of one part to eighty of water, disappeared so completely in the rectum that an evacuation one hour afterwards was found to contain no more than the usual proportion of salt. (_Animal Chemistry_, _p._ 77.)

On the mucous surface of the small intestines are a number of small projections, called Villi. Within these are the origins of the Lacteals, a peculiar set of Lymphatic vessels, which are engaged in the absorption of chyle. This chyle is a thick fluid which is formed by the meeting of the Bile and Pancreatic juice with that part of the digested food which passes into the Duodenum. It is generally white, from the presence of fat. Now these lacteal vessels are no doubt absorbent, but are they ever engaged in the absorption of medicinal solutions? It seems that they are not in ordinary cases at all concerned in this; for three chief reasons. In the first place it appears from the researches of Bernard and others that the lacteal system is a special arrangement for the absorption of fatty substances, and that other matters, such as albuminous compounds, pass generally into the veins, and thence to the liver. Besides, it seems that these lacteal absorbents are only in action during the digestion of food, when the epithelium on the surface of each villus becomes loosened, in order to allow to the chyle an easier access to the lacteal within it.[21] So that it is likely that a small portion of a fluid or soluble substance would be insufficient to rouse them to action. And, inthe third place, direct experiments of a decisive kind have been made on this point. Magendie has found that the ligature of the lacteal trunks does not prevent the occurrence of poisoning from agents introduced into the bowels. And Tiedemann and Gmelin have carefully sought in the chyle for a number of different medicines administered to animals in their food, and have been unable to detect any of them there. So that, with the exception perhaps of fats and fixed oils, we may reasonably conclude that no medicinal substances pass into the system through the lacteals, but that all are absorbed by the veins or capillary vessels.[22]

It seems probable that the Bile and Pancreatic juice may be engaged in reducing to a soluble state certain medicines that are insoluble in the Gastric secretion, and may thus procure the absorption of these substances by the veins of the intestinal canal.

Having briefly considered the secretions which meet the medicine on its first entrance into the system, we are next to inquire into the manner in which this medicine gains admission into the blood. In the first place, it must be in a fluid state, or it cannot be absorbed at all. It will be most convenient to consider afterwards how different remedies are to be reduced to this condition.

Now the force or process by which fluids are enabled to pass and repass through an animal membrane, has been named by Dutrochet _Endosmose_ and _Exosmose_, according as the current tends inwards or outwards.

There are fluids on both sides of the membrane. The circumstances which determine their passage are mainly 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 membrane._--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. By virtue of the last two laws, but contrary to the first, water passes through to alcohol more rapidly than alcohol to water. 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. This also will cause endosmosis in defiance of the first law. This may be proved by a simple experiment. Let a large vein, cleanly dissected, be attached at one end to the stopcock of a vessel containing pure water. Let it then pass through a basin containing a strong solution of Ferrocyanide of Potassium, and let the other end hang over a jar filled with a solution of the Sesquichloride of Iron. If the cock be now turned, and water be allowed to pass through the vein into the vessel beyond, the solution of Iron will quickly acquire the tint of Prussian blue; for the heavy solution in the central vessel has passed through to the simple water of the vein, mainly by virtue of the motion of the latter. It will be seen directly that this is a matter of considerable importance. 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. (_Vide Liebig's Animal Chemistry_, p. 72; _Liebig on the Motion of the Juices_; and the _Lectures of Professor Matteucci of Pisa_.)

The mucous membrane and the coat of the capillary vessel beyond it are probably subject to about the same physical conditions of absorption as those which are thus found by experiment to regulate the passage of fluids through dead animal membranes.

As to the first condition, it is probable that the aliment or medicine which is digested, however solid and dense, may be diluted down by the gastric juice until the solution is of less specific gravity than the serum of the blood. With the second law we are not so much concerned, as the medicine after solution has generally no repulsion for the animal membrane. So also with the third, as the serum of the blood mixes readily with all watery fluids. The fourth, viz. the condition of motion, is of great importance; for by it the motion of the contents of the capillary vessels will tend powerfully to determine the passage through of the liquid on the other side. Fifthly, the influence of pressure on endosmosis is one which is certainly exerted in the case of the stomach and intestines, which are muscular, and during the process of digestion contract on their contents with considerable force. This contraction, together with the circulation of the blood in the capillaries, would doubtless be sufficient to determine the passage of the digested matters inwards, even in opposition to the first law.[23]

Under the first proposition I have shown that the majority of medicines are absorbed into the system. It is now seen where and how they are absorbed. But it still remains to be seen what particular substances or classes of medicaments are thus taken into the blood, and whether while so passing they undergo any modifications.

The following, then, are the chief classes which I believe to undergo solution and absorption in the intestinal canal. They comprise the great majority of all substances used either as food or medicine:--

1. Mineral substances soluble in water. 2. Mineral substances soluble in acids. 3. Mineral substances soluble in alkalies. 4. Vegetable products soluble in water. 5. Animal and vegetable substances rendered soluble by the gastric juice. 6. Fatty and resinous substances soluble in alkali.

1. All soluble mineral substances--acids, alkalies, salts, and soluble compounds of the earths and metals--are absorbed in the stomach and intestines. The conditions and the process of absorption have been already stated. When solid they are first dissolved, when in a dense solution diluted down by the gastric fluid before they are absorbed. Thin watery liquids are quickly taken up. Motion on one side, and pressure on the other, hasten the process. I am not inclined to make any exception to this rule. This leads me to make some remarks on _the Endosmotic theory of the action of saline purgatives_.

M. Poisseuille found that the serum of the blood would pass through an animal membrane to a solution of Sulphate of Soda of greater specific gravity. He thus concluded that an ordinary saline purgative of greater specific gravity than serum (1.028) acted by causing the passage of this serum outwards into the intestine, producing a watery evacuation. The theory was taken up by Liebig and Matteucci, and by Laveran and Millon. Dr. Pereira and Dr. Golding Bird have drawn some practical inferences from it.

It is said that when a saline is absorbed it produces diuresis, and no purging; that when it purges it is not absorbed; that when given to act on the kidneys, the solution should be so diluted as to contain less than five per cent. of the solid; and when administered as a purgative, the specific gravity should be considerably above 1.028. Now I do not deny that a weak solution is more likely to pass off by the kidneys, and a dense one by the bowels; but I consider this due to the fact, that the kidneys are the proper emunctories of water, and of such matters as are soluble in it. But I believe that these solutions are equally absorbed, both heavy and weak, and that the purging or diuretic effect depends mainly on the quantity of the salt, as the kidneys will not eliminate beyond a certain amount of it. I must allege, to support this view of the question, firstly, some arguments _à priori_; and secondly, some experiments which I have made to satisfy myself. To consider first the former. Analogy is certainly against this theory. Other purgatives from the vegetable kingdom produce their effect when injected into the blood, and are yet often powerfully hydragogue. What effect on the process of endosmosis can be exerted by Castor or Croton oils, or by calcined Magnesia? On turning to what we know of the theory of digestive endosmosis, we find that the solid parts of the food are diluted down so as to be absorbed, and that the influence of pressure is to be taken into calculation. It was laid down by the great Boerhaave that a necessary requisite for the formation and absorption of chyle was the contractile force of the viscera. (_Van Sweiten's Comment_, vol. i. p. 290.) This, in fact, would press the fluid into the absorbent vessels, even if against the other endosmotic forces. Further, a fundamental principle was insisted on by Dutrochet--that even when the liquids on the two sides varied in density, they would both pass through to each other, though in different proportions. The ultimate result of this would be, that a heavy saline solution would be diluted down to the specific gravity of the serum, and would then pass through. This point I have illustrated in my first experiment. Thus it seems that my view is favoured by these physical laws. But even if it were not so, I should not be inclined to admit that all the endosmotic processes in the living body were regulated by merely physical tendencies. This cannot be the case with some of the secretions. The bile is of higher specific gravity than the serum of blood. Urine in health is lower, but in diabetes often much higher. The production of these secretions, differing in density from the serum of blood, would be inconsistent with the first law of endosmosis. Lastly, we find that in many known cases the theory which I am contesting does not hold good. Seidlitz water and sea-water are both known to be purgative. In both the specific gravity is _below_ that of the serum of blood.

The first, according to Bergmann, has a density of 1.006. It contains in each pint 192.8 grains of solid matter. Out of this, 180 grains consist of Sulphate of Magnesia.

Sea-water has a specific gravity of 1.026, and its solid contents are about 3.5 per cent. But Dr. G. Bird says that less than five per cent. of saline matter constitutes a liquid diuretic.

These, then, are strong reasons against this idea considered merely as a theory. But it can readily be put to the proof. With this purpose I have made the following experiments. As far as they are concerned, they seem to show that salines are in all cases absorbed, and that whether they are subsequently excreted through the kidneys or by the bowels depends more on the quantity administered than on the degree of dilution of the dose.

EXP. 1.--A sufficient quantity of white sugar was dissolved in four ounces of water to raise its specific gravity to 1.028, that of the serum of the blood. Two drachms of sulphate of magnesia were dissolved in another ounce of water, so that the solution measured nine fluid drachms, and had a density of 1.060. This heavier solution was introduced into an open wide tube, closed completely below by a clean piece of bladder. It was introduced into a small vessel containing the solution of sugar, and arranged so that the height of the two liquids should correspond. After three days, the inner solution measured two drachms more, and the specific gravity had sunk to 1.050. The outer solution, after making up exactly the loss by evaporation, was found to have risen in density to 1.040. On adding a small quantity each of the solutions of phosphate of soda and carbonate of ammonia, a copious precipitate took place, indicating the presence of magnesia. Thus it appeared that the fluids passed both ways, some of the heavy solution of magnesia finding its way through to the lighter solution of sugar. The tendency of this process was evidently to an equalization of their densities, both by endosmose one way and by exosmose the other. Thus, apparently, would it be with a saline purgative, and with the serum of the blood.

EXP. 2.--Three drachms of Sulphate of Magnesia (a very mild purgative dose) were dissolved in ten ounces of water, and thus administered to a healthy young man. It produced, after some time, slight purging, and some diuresis. The urine, when tested, contained only a very little more than the usual quantity of magnesia. The quantity in the dose was less than five per cent. of the solution, and thus, according to the endosmotic theory, should have produced no purging.

EXP. 3.--Six drachms of the same salt were given in eighteen ounces of water to the same patient. After a few hours, it caused very copious and long-continued watery purging. The urine did not seem to be increased, and contained no excess of magnesia. It seemed, that in spite of the dilution, the quantity of the salt was so large, that it could not pass off by the kidneys, and so was eliminated from the blood by the bowels, in the same way as other purgative medicines. (_Vide_ Chap. IV.)

EXP. 4.--This trial was the reverse of the last. Two scruples of Acetate of Potash were dissolved in three drachms of water, and thus administered. The solution then contained about twenty per cent. of the salt. According to the endosmotic theory, it should have caused only slight purging, on account of its density. It did not do so, but produced diuresis. The dose was so small, that after absorption it was easily eliminated by the kidneys.

These experiments are in favour of my views, and seem, as far as they go, to cast discredit on the theory of Poisseuille. It will be very easy to multiply them, so as to place the fact beyond a doubt.[24]

This point being so far settled, and there being no physical reason why any other soluble mineral substance should not be absorbed--it being, moreover, proved, by repeated experiments, that they all pass into the blood, we therefore proceed to the second class of bodies capable of absorption.

2. Mineral substances soluble in acids.--It is apparent that if any insoluble substance will admit of easy solution in the fluids of the stomach and intestines, it may be brought to the condition of a soluble one and thus absorbed. Now the gastric juice is acid. This secretion has been variously ascribed to free hydrochloric, acetic, phosphoric, and lactic acids; also to an acid phosphate or lactate of magnesia. There seems to be most reason to conclude that it is lactic acid, which would be easily formed out of the constituents of the food.[25]

But we have now only to regard the gastric juice as containing a free acid. This would reduce to solution the carbonates and oxides of all the metals; less perfectly when anhydrous, more easily when in the hydrated form. In this manner are absorbed the oxides of Iron and Silver, the carbonates of Lime and Magnesia, and other medicines of the same kind. They would be slightly modified, being absorbed in combination with the (lactic) acid of the stomach. In this they would differ somewhat from the substances already soluble, which would probably be absorbed unchanged, unless we except the alkalies and their carbonates, which might be similarly decomposed. Even these, if given in solution, would probably be absorbed faster than the gastric acid could be secreted to neutralize them.

Other insoluble substances, such as calomel and metallic sulphurets, would be more or less dissolved by the action of this acid. But as a great part would necessarily escape its influence, being propelled onwards by the muscular contraction of the stomach, it follows that insoluble substances of this kind are much less active as medicines than similar compounds introduced in a soluble state. It is also likely that a certain quantity would be sufficient to exhaust for a time the acid gastric secretion.

We now pass on to a third class of mineral products, which, though insoluble both in water and in acid, yet, being soluble in alkalies, appear to be in this way prepared by absorption.

3. Mineral bodies insoluble in water and in acid, but soluble in alkalies.--These remain unaffected by the action of the gastric juice, but on passing on as far as the centre of the duodenum, they meet with two alkaline fluids. These are the bile and the pancreatic juice. We know that some such insoluble bodies pass into the blood. It will be shown in the proof of the next Proposition, that they cannot do so without being first dissolved. Therefore, there must be in the intestinal canal something capable of thus dissolving them. For this purpose these two alkaline secretions are well adapted. As an example of such mineral bodies, of which there are not many, I may adduce sulphur. It unquestionably passes into the blood, and is found there in combination with alkalies, as a sulphuret or sulphate. It has been detected in the urine of those who were taking it, by Dr. Ronalds and others. It is possible that iodine, bromine, and some of the hydrated metallic oxides; may enter the blood in the same way.

4. Vegetable substances soluble in water.--These would be absorbed with more or less readiness according to their degree of solubility. They would probably be taken up in great part by the stomach. Some vegetable matters--as Lignine, or woody fibre, and Resins--are insoluble in water. Starch even is comparatively insoluble, and thus comes under another division, being probably one of those vegetable substances which are rendered soluble by the aid of the pepsin of the gastric juice.

These soluble vegetable matters are of several kinds. Cane-sugar and grape-sugar are readily soluble. So also are the various vegetable acids. There is another class of bodies which is highly important in a medical point of view. These are the natural salts of the vegetable alkaloids, of which are constituted so many of the active principles of plants. In pharmaceutical operations we are enabled, by the judicious employment of different menstrua, to extract from the crude and inert mass these vegetable active principles, and thus to obtain in a concentrated form the medicinal power for which each plant is esteemed. This process is also performed in the stomach. By digestion and concoction, with or without the aid of acid, it is enabled to dissolve out these soluble and potent matters from the ligneous and bulky tissues which surround them. For though the alkaloids themselves are in general almost insoluble in water, yet their natural salts which occur in the vegetable kingdom are mostly very soluble. The most important of these salts are as follow. In Cinchona bark, the Kinates of Quina and Cinchonia. In Opium, the Bimeconates of Morphia and Codeia. In Nux Vomica, the Igasaurate of Strychnia. In Aconite, the Aconitate of Aconitina. In Colchicum and Sabadilla, the Supergallates of Colchicia and Veratria. There are some neutral soluble substances, not partaking of the nature of Alkalies. Thus we find in Ipecacuanha and Ionidium, Emetine; in Tea and Coffee, Caffeine; in Willow-bark, Salicine; and the soluble active principles of Senna, Aloes, and Gentian, are probably of the same nature. Many other alkaloids are known. Atropia in Belladonna, Daturia in Stramonium, and Hyoscyamia in Hyoscyamus, occur in combination with Malic acid. Conia in Hemlock, and Nicotia in Tobacco, are peculiar volatile alkalies containing no Oxygen: thus in two respects they resemble Ammonia. They too are soluble in water.

Alcoholic and Ethereal fluids may be enumerated here as soluble products of the vegetable kingdom. Alcohol mixes with water to any extent; and one part of Ether is soluble in ten parts of water. Nitric Ether and Chloroform are also sufficiently soluble. So is Creosote, 1.25 parts of which dissolve in 100 of water. But this may be absorbed in another way, as will be seen presently. Volatile Oils and Turpentine come also under this head. They are all slightly soluble in water. The former, when given in small doses, are probably absorbed in this way. Turpentine, when given in large doses, may perhaps, by undergoing a change, come under the head of vegetable substances dissolved by alkalies. Camphor may be included here: one part is soluble in 1000 parts of water.

The soluble gummy matters of plants, when added to the substances enumerated above, constitute an aggregate which is called the _watery extractive_ of a vegetable product: _i.e._ that part which is capable of being dissolved out of it by pure water.

But there are other active parts of vegetables, such as oily and resinous matters, and some neutral acrid principles, which, before they can be dissolved by water, require the aid of an alkali. These will be considered separately.

We now arrive at a fifth class of matters which are taken up by absorption.

5. Animal and vegetable products dissolved by the gastric juice.--The most important of these are the nitrogenous and nutritive constituents of the flesh of animals and of the parts of vegetables. Albumen, Glutine, Fibrine, and Caseine, are connected together as compounds of Proteine. Animal Fibrine, and the analogous Glutine of vegetables, are quite insoluble in water. Albumen and Caseine, though soluble, are immediately precipitated by acids. This is known to be at first effected by the gastric juice on their entry into the stomach. But the action of the gastric juice which contains an acid, and a peculiar nitrogenous material called Pepsin,--together with the temperature of the body, which is about 100°,--causes at length the gradual solution of these previously insoluble matters. This is found to take place out of the body when the above conditions are imitated with an artificial gastric fluid. The result of the process is a viscid fluid, which is then absorbed. The hard Gelatine of gristle and bone is not soluble in water at this temperature, but is readily soluble in the acid gastric juice. The Pepsine seems to be an important agent in this process, for an acid by itself is found to produce an imperfect solution. The nitrogenous matters thus digested and absorbed constitute that portion of the food which is of most use in the nutriment of the system; for the starchy compounds cannot be appropriated to the more solid tissues, although in some cases they may be converted into fat, as in herbivorous animals. (Liebig's _Animal Chemistry_, p. 113.)

Starch itself is one of this class. Tiedemann and Gmelin found that by the action of the gastric juice it was slowly converted into Dextrine, which afterwards changed into grape sugar. Both of these are very soluble. From the researches of Bouchardat and others, it appears that other fluids, as the Saliva, the secretion of Brunner's glands, and the Pancreatic juice, possess also this power of converting starch into a more soluble compound. So that if any of it escape the action of the stomach-secretion, it is probably reduced to solution and absorbed in the small intestine.

This change of starch is the first of a series of transformations, now ascertained, the ultimate result of which is its combustion and resolution into carbonic acid. Thus the nitrogenous compounds are called the _nutritive_, and the starchy materials the _calorifacient_ elements of the food. Considered as medicines, these substances belong to the division of Aliments.

6. We have already considered some few mineral substances which are absorbed by the aid of the free alkali contained in the Biliary and Pancreatic secretions.[26] The sixth kind of absorbed matters consists of some vegetable and animal products which can only be rendered soluble by a similar agency. Fats and oils, resinous matters, and some principles resembling resins, come under this head. Fats and fixed oils consist of acids, as Stearic, Margaric, and Oleic, insoluble in water, in combination with a base, Glycerine, which, when isolated, is soluble. With a free alkali such a fat forms a soluble salt, called a soap, and the base Glycerine is set free.

In Man the Bile and Pancreatic juice are discharged together into the middle of the Duodenum. The fatty matters of the food are not absorbed before they meet with these secretions. But, after they have mixed with them, a milky fluid, called chyle, is formed, which is then taken up by the lacteal absorbents. It passes thence into the Thoracic duct, meeting there with an albuminous lymph, and is discharged at length into the general circulation at the junction of the left jugular and subclavian veins.

M. Bernard, in some papers laid lately before the French Academy, states, as the result of his experiments, that the function of the Pancreatic juice is to reduce the fat to the condition of a white emulsion. He states that no milky chyle is formed when the Pancreatic ducts are tied in dogs. He considers it absolutely necessary that saccharine and albuminous matters should be absorbed by the capillaries of the Portal veins, and then pass through the liver; and believes that the sole function of the lacteals is to take up fat thus emulsified. His experiments and inferences have received the high sanction of M. Magendie.

M. Frerichs has since affirmed that, whatever be the function of the Pancreatic juice, the Bile, by virtue of the alkali which it contains, is an indispensable agent in the absorption of fats. But M. Bernard has also found that the Pancreatic juice is always alkaline in health.

Whatever be the particular function of the Bile, it may reasonably be concluded that the alkali contained in one or both of these fluids is engaged in the saponification and solution of the emulsified fats. If it were not for this, this alkali would seem without an object; and further, it is contrary to all we know of the process of absorption to suppose that oil could pass through to a watery fluid without the intervention of an alkali to reduce it to the soluble state.

Thus it would seem likely that by means of the Pancreatic juice, with or without the aid of the Bile, fatty matters are first emulsified, in order to undergo an increase of surface, and then again saponified before they can be absorbed by the lacteal villi.

The principal fixed oils which are used in medicine are Castor, Olive, Almond, Croton, and Cod oils. It is certainly to be regarded as a very beautiful arrangement in the animal economy, that those substances which are not acted upon by an acid fluid should be subsequently subjected to the action of a free alkali, so that by the successive action of these solvents, together with the peculiar process of stomach digestion, the great majority of substances taken into the system are dissolved and rendered fit for absorption.

There seem to be other vegetable substances which are rendered soluble by means of alkali in the way already described. Resins form an important class of remedial agents, in which are comprised many Diuretics, Diaphoretics, and Purgatives. They consist chemically of peculiar acids, which, though themselves insoluble in water, combine with alkalies to form salts which are soluble. They are certainly in most cases absorbed. They have been found in the blood, and detected when passing out in the urine. From this last they may be precipitated by an acid, indicating that they are held in solution by an alkali. In large doses they may not be absorbed, but by irritating the surface of the intestinal canal, may act externally as Cathartics, and be expelled by the peristaltic action which they excite. But in small doses they enter the circulation in solution, and affect remote organs. The only way in which they can be dissolved is by means of the alkali of the two intestinal fluids. Among resinous medicines I may mention Catechu, Kino, Benzoin, Storax, Peru and Tolu, Copaiba, Guaiacum, the fetid resins, etc. Many purgative drugs, as Jalap, Scammony, and Gamboge, owe their efficacy to resin.

There are moreover certain neutral acrid principles, similar in their nature to resins, which are soluble only in alkalies, and thus come under this head. Such are Cantharidin, Piperin, Pyrethrin, Colocynthin, Elaterin, and Capsicin, obtained from Cantharides, Pepper, Pyrethrum, Colocynth, Elaterium, and Capsicum. But it should be observed that some of these are soluble in Acetic acid; and if, as some have supposed, this acid exist in the gastric juice, then they might be dissolved in the stomach.

We may add here some medicines which were enumerated also in a former division. Creosote, not very soluble in water, is easily dissolved in a free alkali. This substance also, like the last, is soluble in Acetic acid.

Some volatile oils, especially Turpentine, display a marked tendency to oxidize into resins; and being themselves very sparingly soluble in water, may perhaps be dissolved after having undergone this change. Thus Turpentine changes into common Resin, which consists of two isomeric acids, Pinic and Sylvic.

Turpentine = C_{20}H_{16} Pinic Acid = C_{20}H_{15}O_{2}

and,

C_{20}H_{16} + 3O = C_{20}H_{15}O_{2} + HO.

or, Oil of Turpentine, with the addition of three atoms of Oxygen, produces Pinic acid, _i.e._ Resin, and an atom of water.

Now Turpentine, when given in large quantities, irritates the surface of the intestinal canal in man, and is not absorbed. But in the horse very large doses are found to pass through the system into the urine. It is not likely that a large quantity should enter in solution in water. It seems more probable that it may first in some way become oxidized, and then dissolved as a resin. The action of turpentine resembles that of some other substances which contain resin, as Copaiba and Balsam of Peru.

The resins thus dissolved would pass, like other solutions, through the mucous membrane of the intestines into the Portal capillaries.

But of the fats and fixed oils it cannot be said to be _proved_ that they are absorbed in a state of solution, although such a conclusion is almost forced upon us by a consideration of the laws of endosmosis. They do not pass into the veins, but are taken up by the lacteal absorbents. They are _capable of solution_, and are thus not in that sense an exception to the rule of Prop. II. But in another sense they are an exception to it; for they do not pass directly into the veins, but through the lacteal system. It seems that the sole purpose of these lacteal vessels is to absorb fats. Thus it appears that all soluble substances, whether in the food or given as medicine, and in whatever manner rendered soluble, whether by acid, by alkali, or by stomach digestion, are absorbed in the stomach and intestines. All of them, with the exception of fatty matters, pass directly into the blood, traversing the mesenteric and Portal veins, to reach the liver. From this organ they pass on into the heart through the Vena cava inferior. I have shown also that they are mostly absorbed without material change. Supposing the stomach acid to be lactic, it would be too weak to displace mineral acids. It would, however, decompose a few insoluble matters, and combine with alkalies and their carbonates, forming salts which in the blood would again change into carbonates. (_Vide_ Prop. VI.)

PROP. III.--_That those medicines which are completely insoluble in water, and in the gastric and intestinal juices, cannot gain entrance into the circulation._

It may at first sight be objected to this proposition, that fatty matters may probably enter the lacteals in an undissolved state. But this is not proved; and besides, whether dissolved or not, we know that they are soluble in one at least of the intestinal juices--viz. the Bile. So that they do not come under the above definition.

We have just seen that many medicines which are given in the insoluble form are capable of being dissolved in the fluids of the intestinal canal. This so much reduces the list of perfectly insoluble medicines, that it is difficult to find any that come under such a definition. But Charcoal, the simple metals, woody fibre, and Nitrate of Bismuth, will serve as examples.

Sulphate of Lead is often quoted as perfectly insoluble; but this is not the case. It is soluble in a solution of acetate of ammonia. This salt is contained in the perspiration. Thus the sulphate, when substituted for the carbonate in some lead works at Paris, proved fatal to the foreman, who died of colic. M. Flandin found that it poisoned a dog when rubbed into the skin as ointment. Even some metals may possibly be brought within the influence of weak acids when in a fine state of subdivision, as Mercury in blue-pill. Gold in a very fine powder has been used successfully in syphilis.

Thus the list of insoluble substances is still further reduced. But there is no doubt that many substances which are slightly soluble in the intestinal fluids may in great part escape this solution, and pass out with the fæces just as they went in.

To assert that the particles of an insoluble substance cannot pass through the homogeneous wall of the capillary or absorbent vessels, is merely to state what follows from an absolute physical law, and is generally admitted by physiologists. But even this fundamental datum has been lately attacked.

Professor [OE]sterlen of Dorpat has been induced to affirm the possibility of the absorption of insoluble substances, from some experiments which he has made. Finely-powdered charcoal was administered to rabbits for some days. They were then killed, and globules of charcoal, measuring from 1/6000 to 1/3000 of an inch, were found in the blood of the Portal circulation. (_Zeitschrift für Rationelle Medizin_, 1847.) To obtain these results the microscope was used, a far less certain test in such matters than chemical analysis. [OE]sterlen reasonably concludes that, if charcoal can so pass, so also can any other insoluble substance. The necessity of solution could then at once be done away with, and the blood continually liable to admixture with all kinds of heterogeneous and crude materials. [OE]sterlen asserts further that he has found minute globules of mercury under the skin after rubbing in mercurial ointment. (_Journal für Praktische Chem._, No. IX. 1850.) Now, if these things were true, there could be no need to suppose the solution of insoluble active medicines, for they would be enabled without difficulty to pass through in an undissolved state.

To test for myself the accuracy of such statements, I have made some experiments, the object of which is to discover if some of the most insoluble of our known remedies, which are yet known to obtain entry somehow into the blood, could do so while yet in the insoluble state. They are as follow:--

EXP. 1.--Ten grains of calomel were given to a large dog. It was killed after three hours, allowing this time for digestion. A considerable quantity of blood was collected from the Portal vein, and submitted to analysis to determine whether it contained any compound of Mercury in an insoluble form. The blood was dried and pulverized. The result was boiled for some time in water, and the insoluble part collected. It was dissolved in a small quantity of aqua regia, and the clear acid solution placed in a test tube. A slip of zinc foil was folded round a narrow plate made of gold foil, and introduced into the solution. A galvanic current being thus set up, the minutest quantity of mercury, if present, would have been deposited on the gold, so as to tarnish it. But this did not take place, and when at last the zinc was completely dissolved, the gold remained as bright as before. Thus there was _no_ Calomel, or compound of mercury, present in the insoluble form.

EXP. 2.--Ten grains of strong mercurial ointment (containing half its weight of metallic mercury, with some oxide) were given to another dog. He was killed after the same time, and the Portal blood analyzed carefully in the same way, but here also _no_ mercurial compound was present in the insoluble form.

EXP. 3.--To a third dog five grains of Oxide of Silver were administered. After three hours he was killed. The Portal blood was dried in a water-bath, and reduced to powder. This was boiled for some time in water, which was separated by filtration. Aqua regia was then boiled on the insoluble part. This would convert any silver into chloride. The acid was evaporated off as much as possible, and the solid remainder heated in a small porcelain crucible to dull redness. The result was powdered, and digested in liquor ammoniæ. It was filtered, and excess of nitric acid was added. There was not any precipitate. Had chloride of silver been present, it would have been dissolved by the ammonia, and precipitated by the acid. Thus no insoluble silver compound was contained in the blood analyzed.

EXP. 4.--Ten grains of sulphur were administered in the same way to a fourth dog. On killing it and opening the body, the thoracic duct was found to be full. A considerable quantity of chyle was collected from it. Now, as it is asserted by some, that fat passes undissolved into the chyle, and as I believe that sulphur is digested in the neighbourhood of the bile duct, this chyle was chosen for analysis in preference to blood, as more likely to contain any insoluble sulphur. Besides, the blood would be less satisfactory, on account of the large quantity of albumen and fibrine contained in it, both of them also containing sulphur. The insoluble part of the chyle was obtained in the same manner as with the blood. It was then boiled in a small quantity of a weak solution of caustic potash. By this any free sulphur would be converted into a soluble sulphate of Potassium. The solution was filtered, and a few drops of a solution of the Nitro-prusside of Potassium added. (This is a salt lately discovered by Dr. Playfair. It is a delicate test for soluble sulphurets, with which it strikes a deep purple colour.) No change was produced. Therefore no insoluble sulphur was present in the chyle.

The results of these experiments are thus in direct opposition to those of M. [OE]sterlen, and support a view of the question which seems even _à priori_ more philosophical and reasonable than that which he has adopted. I believe that no insoluble medicine can in any way gain entry into the blood without first undergoing solution in some way or another.

PROP. IV.--_That some few remedial agents act locally on the mucous surface, either before absorption, or without being absorbed at all. That they are chiefly as follow:_--

_A. Irritant Emetics._ _B. Stomach Anæsthetics._ _C. Irritant Cathartics._

It has already been shown, during the consideration of the first proposition, that medicines which act on distant parts of the body must be, and are, absorbed before they can so act. This necessity for absorption has been shown to extend even to medicines which act most rapidly on the nervous system. If any medicines could produce a distant effect by a mere contact with the coats of the stomach, such a power would be ascribed to those stimulants and sedatives which, from the suddenness of their action, are called diffusible. Such are Hydrocyanic Acid and Ammonia. Their rapidity of action is to be ascribed to their volatility, whereby they spread over a large surface, and are almost _suddenly_ absorbed and transmitted through the blood. But Hydrocyanic Acid may be absorbed from any surface. It is poisonous when inhaled into the lungs. It rapidly causes death when dropped into the eye of an animal. So also the results of the inhalation of ammoniacal gas are the same as of the ingestion of its solution. I believe that the latter, on account of its diffusibility and rapid absorption, escapes neutralization by the stomach acid, and passes into the blood as free Ammonia.

In the consideration of the first Proposition, I endeavoured to point out that though the proper action of a medicine could in no case be conducted, without absorption, from the mucous surface to a distant part of the system, yet that a remote action of another kind might occur as the result of a change in the nervous system produced by a powerful local impression. I stated that the term _Counter-irritation_ was employed to express this action, the nature of it being but ill understood. A powerful impression on any surface of the body, external or internal, seems to be capable of arresting and diverting, as it were, the attention of the system, and thus, for a time, of checking a morbid process.

Frictions and Sinapisms act on the skin externally on this principle. So do Blisters and Issues; but they are not simply counter-irritants, for they also drain away the serum of the blood. It is not now within my province to consider such an action on the skin, any further than for the purpose of stating that similar local impressions on the mucous surface of the stomach and intestines are capable of operating on the same principle.

We have then to consider what are the local actions that medicines are capable of producing on these surfaces.

And first, it must be laid down as a rule, that all medicines, when given in excess, act as irritants on the stomach and intestines. This is more especially the case with mineral salts, with the bitter and astringent principles of vegetables, and with acrid and resinous matters. By irritating the stomach locally, they cause vomiting; by causing peristaltic action of the bowels, purging. Some of them are actually employed to produce these effects, and will be presently specified.

The corrosive and narcotico-acrid poisons may produce by this local action a degree of irritation sufficient to cause death. In the case of the first, some erosion of the mucous surface may occur. By both kinds violent vomiting and purging is apt to be produced, and succeeded by symptoms of collapse. These last, however, are not _therapeutic_ agents, when in such doses.

Antidotes, employed to counteract these poisons, are remedies which are given to act locally in extraordinary cases. There are three chief kinds of them; Demulcents, to sheath the irritated surface, and protect it from further injury; Emetics and Purgatives, to get rid of the poison; and chemical antidotes, to neutralize it or render it insoluble while in the stomach. With this last object, acids are given in alkaline, and alkalies in acid poisoning. The soluble salts of Lead may be precipitated and rendered insoluble by sulphuric acid or sulphates. Those of Mercury, Copper, and Zinc, by albumen. Tannic acid precipitates the vegetable alkaloids. There are some other special antidotes of the same kind.

Let us now consider the three kinds of remedial agents in ordinary use, which are employed for the purpose of producing a local effect on the mucous surfaces, before absorption, or without absorption.

_a. Irritant emetics._--Two kinds of medicines are employed to produce Vomiting,--specific emetics, and irritant emetics. The former act from the blood; the latter, by local irritation. In the same way that irritation of the external surface of the body will sometimes cause at the same time the _direct_ contraction of a neighbouring muscle, and the _reflex_ contraction of others at a distance, so does local irritation operate on the surface of the stomach. On the one hand the muscle of the stomach itself is caused to contract, so that, the pylorus being at the same time forcibly closed, it tends to expel its contents in the wrong direction. On the other hand, a large set of distant muscles is thrown into sudden action. First, a quick deep breath is taken by means of the inspiratory muscles. Then the aperture of the glottis is spasmodically closed, so that, the lungs being full, the diaphragm cannot be pushed upwards. Then immediately the abdominal muscles contract, and being unable to act on the diaphragm, they press on the stomach, emptying it forcibly of its contents.

All this is by reflex action, and follows sympathetically the contractions of the stomach, co-operating with it, and resulting, like it, from irritation of the sensitive mucous surface.[27] Such is the action of an irritant emetic.

Now, Tartar Emetic and Ipecacuanha do not act in this way. When injected into the blood elsewhere, in sufficient quantity, they are found to produce vomiting. They have also special actions on the heart and lungs, which are not possessed by merely irritant emetics. They seem to me to act specifically on the Vagus Nerve, which is supplied to these organs as well as to the stomach, and to cause vomiting by deranging its functions. By this action on the Vagus while in the blood, they excite, in a special way, the same reflex contractions which are produced, in the case of an irritant emetic, by irritation of the extremity of that nerve in the mucous membrane. They are thus Neurotics, or nerve-medicines. They are not gland-medicines; or, at least, there is no proof that they are excreted by the stomach, and thus they do not come under my definition of Eliminatives. All substances which touch the surface of the stomach cause it to pour out its secretion.

Specific emetics cause nausea, even without vomiting, depressing the action of the heart by their influence over the Vagus nerve. Irritant emetics scarcely cause nausea, producing only a feeling of discomfort, arising from the inverted action of the stomach.

The Sulphates of Zinc and of Copper; common Salt, and among vegetables, Mustard and Horse-radish, are used as irritant emetics. They cause, by contact and irritation, a large quantity of the gastric juice to be poured out. This, together with the emetic, and any contents of the stomach, is rejected. The process is not followed by much inconvenience.

Such emetics are chiefly used when we wish to unload the stomach of any irritating or poisonous matters; but not when our object is to cause nausea, depression of the heart's action, or relaxation of the muscles. The violent action which they produce may possibly act on remote parts on the principle of counter-irritation. Thus emetics of various kinds are often administered in the early stages of inflammatory disorders, and have been known sometimes to cut them short. But such an effect is much more likely to be produced by a specific emetic, which adds to this counter-irritant action the production of nausea, by which the force of the heart is powerfully depressed, and the pulse reduced. Tartar Emetic, the most powerful of these specific agents, must doubtless be absorbed to a certain extent before it can produce its effect. Thus the important difference between the modes of operation of irritant and specific emetics is, that the former do not produce vomiting when injected into the blood, but act locally; whereas the latter act from the blood on the nerves. (_Vide Prop. VIII., Specific Sedatives._)

_b. Stomach-Anæsthetics._--There is a class of medicines used in Gastrodynia which seem to act locally on the sentient nerves of the stomach, in the same way that Aconite acts on the superficial nerves of the skin. Although the majority of them are subsequently absorbed, yet, in order to exert this particular action, it is not necessary that they should pass beyond the substance of the stomach itself. They do not seem to have any special or peculiar tendencies towards the stomach nerves. But if introduced into the blood elsewhere, they would not pass the nerves of the stomach in so concentrated a form as when coming directly from the mouth, and thus would not be so useful as stomach-anæsthetics. Thus this action depends upon local contact, and is so far a local action.

Hydrocyanic acid, Creosote, and Nitrate (also called Tris-Nitrate) of Bismuth, are the most useful of these medicines. The first two are subsequently absorbed, and pass into the blood. The third is a very insoluble salt. It acts also as an astringent on the mucous surface of the intestine, and is probably the only astringent which is not absorbed. Being insoluble, its action is quite confined to the mucous surface. It may be given safely in very large doses, (as [dram]ss, or even [dram]j.) and it is likely that its anæsthetic action may be in some part mechanical in nature, and depend upon its affording a mechanical sheath to the irritable and painful surface of the stomach. Hydrocyanic acid and Creosote,--general sedatives,--act locally as anodynes to the nerves of the stomach.

_c. Irritant Cathartics._--As there are two kinds of emetics, differing in their mode of operation, so also do there seem to be two kinds of Cathartics. But the distinction between them is not exactly the same. As with the Emetics, one kind seem to act by topical irritation, exciting an outpouring of the intestinal secretions, and causing an expulsion of the contents by exciting peristaltic contraction. But Specific Emetics, which act from the blood, seem to produce their effect by influencing the nerve of the stomach; so that they are Neurotic medicines. Specific Cathartics act differently. They are truly Eliminatives. They exert no influence over nerves, but they operate by passing out of the blood through the intestinal glands. Like Specific Emetics, they must be first absorbed. I will not now enter into the theory of Elimination, which I shall have to consider afterwards, but I wish merely to distinguish between local action on a surface, and specific action on a gland, exerted from the blood. Many substances used as purgatives are capable of absorption, and are absorbed. But it seems that they are not fit to remain in the blood; and after passing round in the circulation, they are expelled by the depurative force at a point near to that at which they previously entered by the laws of absorption, namely, the mucous surface of the bowels. They are most commonly expelled by the glands of this surface somewhere in the lower or fæcal portion of the intestinal canal, which is more engaged in secretion, but less active in absorption, than the upper part. The increased secretion which they excite causes peristaltic action, which expels both it and them, so that they cannot again be absorbed.

Such a specific Cathartic would be capable of acting thus if introduced into the system at any point. Castor Oil and Croton Oil, whether received into the stomach, or injected into the veins, or introduced into the system at any part, equally produce purging. So also do Rhubarb, Aloes, and Senna. The principles of these medicines have been detected in the blood by Tiedemann, Gmelin, and others. Colocynth and Elaterium have also been proved to act specifically.[28]

It is to be inferred from analogy that other resinous Cathartics, as Jalap, Scammony, and Gamboge, must also act from the blood. It has also been shown that both from actual experiment, and from a consideration of the laws of the process of absorption, we must conclude that saline Cathartics are absorbed into the blood before they cause purging.

But we have now to do with Cathartics that act by topical irritation. Which are they? I believe that the same resinous Cathartics which have the power of acting specifically, may have, especially when in large doses, a double action. It has been shown that resins are difficult of absorption; and whether they be absorbed or not, we know that they must irritate the intestinal surface, from the violent griping which often attends their operation. Thus Scammony does not act so well, and does not gripe, when the bowels are lined with mucus. Gamboge and Euphorbium are irritant in an extreme degree, and are therefore too dangerous for general use. The powder of Euphorbium resin has been used as an Errhine, for, by irritating the mucous membrane of the nose, it increases its secretion. This illustrates the operation of irritant Cathartics. A great part of the fæces is secreted by the mucous membrane of the bowel. This secretion a Cathartic may increase by mere contact and irritation; or, being also a specific agent, by absorption and elimination likewise.[29]

Some Cathartics employed as Vermifuges, as the hairs of _Mucuna pruriens_, metallic Mercury, and Tin powder, cannot be absorbed at all, and must act solely and altogether by irritation.

These Vermifuges, or Anthelmintics, are employed for a strictly local purpose--that of killing and expelling intestinal worms. Any powerful Cathartic may be used to expel them. But such an agent should generally be conjoined with a medicine that tends directly to kill the parasite; for after that it will be more easily dislodged. For this purpose the root of Male Fern, Kousso, and the bark of the root of Pomegranate, have been used with advantage in the case of tape-worm. Ascarides are situated low down in the intestine, and may be dislodged by the use of an enema, as of Salt.

Turpentine is often very efficacious in cases of this kind, being at once a poison to the worms and a powerful irritant cathartic.

I have already alluded to Nitrate of Bismuth, as seeming to be an astringent to the mucous surface of the intestine, although apparently incapable of absorption. It has been used with advantage in diarrh[oe]a, and is highly recommended by Dr. Theophilus Thompson in the diarrh[oe]a of Phthisis.

But all other astringents are absorbed; and when they act on the mucous glands of the intestines, it is probably from the blood.

It has been supposed by M. Poisseuille and others that the action of Opium in confining the bowels is to be attributed to a power of checking the process of endosmosis, said to be possessed by a solution of Morphia. I shall afterwards state my reasons for discrediting this explanation. (_Vide Chap. IV., Art. Opium._)

Thus we have concluded the list of substances which seem to act locally on the mucous surface, without passing into the blood.

Having previously endeavoured to explain the various modes in which medicines are absorbed and pass into the blood, and having now defined the action of some few before absorption, the greater part of our investigation remains still to be accomplished. The actions of medicines in the blood, and their various and complicated operations in the cure of diseases, have to be traced out, and, if possible, accounted for.

The remaining six Propositions concern the behaviour of medicines after their passage into the blood. The first two of them are comparatively unimportant. The Fifth is merely an extension of the First Proposition,--in which the same rule is applied to the blood which was there proved of a surface,--and indeed follows in part from the latter. The Sixth Proposition defines three kinds of changes which certain medicines are liable to undergo during their stay in the system.

PROP. V.--_That the medicine, 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._

We might already have concluded that, as a general rule, it is impossible for medicines to exert their primary action on a remote part by nervous or any other agency, but that they must actually reach the part which they affect by means of the circulation. The experiments, already quoted, of Magendie, Blake, Ehbert, and others, show that even those medicines and poisons which tend most powerfully to influence the nervous centres, cannot act by nervous connexion, or without being allowed to pass on in the blood. They must actually reach the brain, before they can act upon it. The circulation of the blood is sufficiently quick to allow of this.

The action of nerve-medicines when applied to a part, being similar to that which follows their absorption, would alone render it highly probable that in the latter case they reached the part in the blood. Thus Morphia, Hydrocyanic Acid, Chloroform, and Aconite, benumb the superficial nerves: Belladonna dilates the pupil; and Strychnia augments muscular irritability; whether locally applied, or administered through the stomach.

Neurotic medicines have even been detected after death in the parts and organs which they influence. Thus Alcohol has been found in the brain, and Lead in the spinal cord and muscles.

From these various facts we may conclude that however near these remedies may be brought to that part of the nervous system over which their power extends, whether it be centre or periphery, they do not in general affect it, unless they are allowed to reach it.

And what is proved of nerve-medicines holds good still more obviously with medicines that act on the blood, and on blood disorders. Nearly all of these have been found to exist in the blood, and to pervade the whole mass of the circulation, wherever at first introduced.

The glands of the body form a third case in which we require proof of actual local access. This matter will be discussed when we have to consider the subject of Eliminative medicines, when I shall attempt to show that the majority of those medicines actually pass through and are excreted by the glands which they affect. When Mercury is chemically detected in the secretions of the liver and bowels; Sulphur in that of the skin; Turpentine and Copaiba in that of the kidneys; it is evident that these substances must have reached bodily the glandular organs to which their action is directed.

Astringents are medicines which from the very nature of their action--apparently a chemical one--cannot operate at all without touching the muscular fibre, which they cause to become contracted.

But in laying down this rule of the necessity of local access for the production of the primary[30] effect of a medicine, we must be careful that we do not make it too absolute. In saying that no action at all can be propagated by the agency of the nervous system, we do not make proper allowance for the vital properties of nerve-fibre. The vital nature of common nerve-fibre is such that two actions can be conducted along it;--an impulse producing sensation, or an impulse producing muscular action, at a distant point. It is known that an impression on the terminal extremity of a sensory nerve is capable of producing either sensation or motion at a distance, by what is called _reflex nervous action_. Though this impression must pass through the brain or spinal cord, yet these centres are not appreciably affected by it. Now it is possible, though it does not often happen, that the action of a medicine on the extremity of a nerve may cause this distant action, without reaching the part at which it is manifested. It may be positively affirmed that in no other case can the direct action of a medicine be conducted along a nerve.

Having made allowance for the physiological characters of nerve, we must also take notice of the vital properties of muscular fibre. We sometimes find, especially in the case of unstriped muscle, that when one part of a muscular organ is caused to contract, a wave of contraction is propagated along the fibres; and this action may even be extended to a neighbouring muscle, either by contact or sympathy. In one or two cases it seems that muscular contraction may occur in this way as the result of the action of a medicine.

We will now consider separately the two exceptional cases.

_a._ _A medicine may occasionally produce pain or sensation at a distant part, without reaching that part._ We often find that a morbid action at one part of the body is capable of producing pain or uneasiness at another distant part by a reflex nervous action. We are familiar with instances of this among the symptoms of disease. The pain in the knee which occurs in disease of the hip-joint; in the left arm, in some cases of heart disease; and in the right shoulder, in disorders of the liver; are examples. Certain impressions on the surface of the stomach may cause such a reflex pain. Swallowing a piece of ice will sometimes produce pain over the brow; and it is likely that the headache which follows over-eating, or a large dose of a tonic medicine, may result in a similar way from mere irritation of the stomach. Any irritant, as a solution of Iron, Arsenic, or Zinc, will do the same. The action of a violent purgative will cause headache while it lasts. Although we cannot deny the possibility of other actions of the same kind, yet there are so few medicines which, in ordinary and safe doses, are capable of producing pain in any way, that it becomes difficult or impossible to adduce a satisfactory example of an agent which operates on distant parts in this manner when in the blood.

_b._ _A medicine may occasionally produce muscular contraction at a distant part, without reaching that part._ This may be done in two ways; either by a reflex nervous action, or by a propagation of the contraction from one muscle to another in its neighbourhood. The first of these never results from the action of a medicine while in the blood; but it may follow an impression on a surface. Thus we have already seen that the irritation of the mucous membrane of the stomach, and probably of the filaments of the Vagus nerve distributed in it, which precedes the act of vomiting, may cause the contraction of the muscles of the abdomen.

The propagation of contraction from one muscular organ to another appears to take place in the case of violent purgatives, particularly some, as Aloes and Savine, which act on the lowest portion of the large intestine, exciting it to a peristaltic contraction,--whose action may thus be extended to the contiguous Uterus in the female, causing it also to contract. This renders the employment of such medicines dangerous in cases of pregnancy, as tending to produce abortion. In other cases these agents may be useful; for by the irritation and congestion which follows this action on the Uterus, they may cause the appearance of the menstrual secretion when deficient or retained. This also is the result of an action on a surface.

Now, though in such cases the action of a medicine seems to be continued from the part where it is situated to a distant point, there are certainly no authenticated examples of such an action by a remedy in the blood. Yet it would not be reasonable to deny the bare possibility of such a thing. But such instances are at all events rare, and, being cases of the manifestation of their vital properties by nerve and muscle, rather than of the proper action of a medicine, must not be considered to invalidate the above proposition, which, as a general rule, is of considerable importance.

PROP. VI.--_That while in the blood, the medicine may undergo change, which in some cases may, in others may not, affect its influence. That these changes may be--_

_a._ _Of Combination._

_b._ _Of Reconstruction._

_c._ _Of Decomposition._

Before advancing to the consideration of the modes in which medicines operate in the cure of disease, it is of importance to mention that some of them are liable to undergo changes in the animal organism, because in particular cases these changes may materially affect their action, and in all cases they have some bearing upon it. With a view to this point I have divided these changes, somewhat arbitrarily, into three kinds,--of which the first does not hinder the effect of a medicine--the second may alter it slightly--and the third entirely changes or neutralizes it. Some of these change have to be considered more at length in the progress of the Essay, so that here I will only give an outline of them.

_Changes of Combination._--The chief, and indeed almost the only way of detecting changes in medicines, is by taking notice of their effect upon the composition of the secretions.

Now in the blood we have a slight excess of alkali; in the urine, an excess of acid. Acids and alkalies are often given as medicines; and as it is not right that there should be much excess of either in the blood, both are generally soon neutralized in the system, and reduced to salts. This may sometimes occur before absorption, but perhaps more often after it. Now, it may seem strange for me to say that this neutralization does not destroy their influence. But it evidently does not; for in being neutralized they diminish in the blood, and in the system generally, the quantity of basic or of acid matter, and thus tend to alter the reaction of the secretions. Though an acid may combine in the blood with Soda, or with salts of Soda, yet by so doing it causes an excess of some other acid, probably an animal acid, which, being set free, acts on the secretion of urine much in the same way that the first acid would have done. It is easier to render the urine alkaline than to make it acid, for two reasons; first, as I shall show hereafter, an acid may pass out through other glands besides the kidneys; and secondly, an alkali is not so easily neutralized, either before or after absorption, the blood being already more or less alkaline.

A large quantity of acid would easily overcome the feeble reaction of the blood, and thus, by remaining free, Sulphuric and other acids are enabled to act as astringents on certain of the glands.

Other changes of combination have already been shown to take place during the process of absorption. Alkalies and their carbonates are more or less neutralized by the stomach acid. Substances soluble in alkalies are probably absorbed in such solution. Calomel, Chalk, Magnesia, and metallic oxides, as well as other insoluble medicines, are taken up in the soluble form, in which only they are capable of acting. But we are now concerned with medicines in the blood. And here I must protest against the idea that all chemical affinities have free play in that liquid. If it were so, many of our most valuable medicines would be decomposed and rendered insoluble there. All the mineral salts would be precipitated by the free Soda in that fluid. Acetate of lead would be immediately decomposed by sulphates, and Nitrate of Silver precipitated by chlorides. It is probable that the vital forces, as well as the viscidity of the plasma, exert a retarding or controlling power over such chemical tendencies.

Some substances are decomposed while passing out of the body. Decomposing matters in the intestines and in the saliva, cause the formation of Sulphuret of Iron, while chaly-beates are taken, which blackens the fæces; and of Sulphuret of Lead, when lead is taken for some time, producing the well known blue line on the gums.

_Changes of Reconstruction._--The elements of a body may be disturbed in the system, and combined together anew, without any material or apparent alteration of its properties. Probably many changes of this kind occur, but only some isolated instances have been verified. Thus Tannic acid, acquiring Oxygen, changes into Gallic. Benzoic and Cinnamic acids are converted into Hippuric acid, which passes out in the urine. Turpentine changes into a volatile oil, which communicates to the urine an odour of violets. Ferridcyanide of Potassium changes in the system into Ferrocyanide. Some of these changes will be afterwards considered more at length.

_Changes of decomposition._--By this I mean such a disarrangement of elements as shall neutralize or reverse the action of a medicine.

There is free Oxygen in the blood, and the most important change to which all organic substances are liable there is _oxidation_.

This probably occurs in many cases. It always takes place with the starchy elements of the food, and with those parts of the nitrogenous tissues that have done their work, and are preparing to be excreted from the body.

By this oxidation Wöhler has proved that the alkaline salts with vegetable acids are changed in the blood into alkaline carbonates. From being first neutral, they become now alkaline in their reaction, and affect the urine in the same way as free alkalies.

(_Vide Hæmatics, ord. Acida, Alkalia, Tonica, Solventia._)

We have now to treat of the actions of medicines in the blood. These are recited in the four remaining Propositions.

The seventh treats of Hæmatics, acting primarily in the blood.

The eighth treats of Neurotics, passing from the blood to the nerves.

The ninth of Astringents, passing to muscular fibre.

The tenth and last treats of Eliminatives, which pass out of the body through the glands.

PROP. VII.--_That a first class of medicines, called_ HÆMATICS, _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._

Supposing that a medicine has fairly passed into the blood, and circulates round with it, there are now two ways in which it may behave itself.

In the first place, it may have a tendency towards some tissues or parts of the body, on which to exert its powers, as the nerves, or the glands, or muscular fibre, and may use the blood only as a vehicle by which most readily and easily to attain to these. Such are Neurotics, Astringents, and Eliminatives. They may not affect the blood, but they must pass through it.

But there is another and still more important class of medicines, whose action is particularly directed towards the blood itself. The blood, after their action, is different from what it was before. It may be a change for the better or for the worse; but there certainly is a change. Medical authors, with few exceptions, have been very backward to acknowledge the existence of medicines of this description. But even those who would fain have classed all medicines as stimulants or sedatives, differing only in the kind or degree of their action on the nervous system, have in many cases been obliged to confess that there is a set of remedies which they call "Alteratives," whose action, though slower, is more certain and more durable than that of the former. It is allowed that they alter the condition of the blood. To suppose that they do so by first influencing the nerves, is to adopt a circuitous and uncalled-for explanation. It is proved that they pass into the blood. It is known that when actually applied to nerves, they do not affect them. From these considerations merely, without further evidence, it would seem tolerably clear that they act by influencing the blood itself, simply and solely. But this it will be my business to prove more at length directly.

Such medicines, then, I have designated Hæmatics, a simple and expressive term which has been used by others before me.

It is obviously necessary that a medicine of this class should be absorbed.

Now some of them tend in the end to act on the nerves or on the glands, not merely indirectly, but by bodily contact. But, whatever their subsequent action, they exert a primary and apparent influence on the blood itself. A little reflection will convince us that these remedies are more efficient than any others that can be selected out of the armory of physic.

It is easy, and satisfactory for the time, to allay nervous excitement by employing a sedative, or by using a stimulant to communicate to the system a temporary strength. It is easy to knock down an inflammation, or to evacuate morbid humours, by stirring up the glands with a powerful eliminative. But these are all at the best but temporary measures. Unless the exigency be also of a temporary character, the disorder may soon return with unabated violence; again is the patient bowed down by its strong hand; again is the fatal termination seen looming in the distance but too distinctly. Then has the physician to call to his aid more potent means, remedies of more permanent and certain efficacy. The disease is in the blood--ever circulating, breeding, and destroying. It is there that it must be met; let the physician strike boldly and warily there, if he would effect a cure.

These medicines, then, act in the blood. How they do so, and in what way they prove of use in the cure of disease, I shall next have to show, while attempting to prove the proposition in which I have briefly stated this mode of operation.

Hæmatics are very numerous, and very important: I shall thus devote some space to their consideration. But I must first lay down a broad distinction between the two divisions of Hæmatic medicines. The diseases in which they are used appear all to originate in the blood, however they may manifest themselves.

Now some of these diseases originate in a want of some principle or constituent of the blood, which want causes an aberration of the vital functions.

Thus, in anæmia, there is a deficiency of the Hæmatosin of the blood corpuscles. In simple debility a want of a similar nature probably exists. In rheumatic fever and other disorders an excess of acid is formed and eliminated, possibly from a want of the alkali by which it should be neutralized. In common inflammatory fever there is an abnormal oxidation of the Proteinaceous compounds, possibly arising, as we shall see hereafter, from a failure of some principles which are the proper food of the oxygen. In diseases causing urinary deposits there is a want of those principles which should naturally retain them in solution. In typhoid fever there is said to be an excess of basic matter, and a deficiency of acid, in the blood. In pulmonary phthisis there is a deficiency of fat in the system. In the latter stage of malignant cholera there is an absence of watery particles in the blood. Some suppose that in scurvy there is a want of the salts of Potash in the blood.

These diseases, then, in some of which the want is proved, in others partly hypothetical, may be treated by medicines which supply the deficient matter, and thus restore a right state of things. They may supply it to the blood directly, or else cause it to be generated there. The former of these modes of restoration seems to be the most frequent, and may possibly, when we shall know more of such matters, be found to occur in all cases. This division of Hæmatics I have named Restoratives (Restaurantia.) Their action, as we shall see, is in some cases apparent, in others more obscure. They restore the blood directly to its proper condition, if there is only a deficiency, but they do not in general seem to have the power of counteracting any morbid or active material that may exist in the blood. Nor do they, except in large doses, exert themselves any peculiar action on that fluid. In these respects they differ from the other division of Hæmatics. They also differ in another important character. Each Restorative has in healthy blood a substance analogous to, or identical with itself: it replaces this when deficient.

Not so with other Hæmatics. There is in general nothing in the blood corresponding to them--or if there be in some cases, they are not introduced with the intention of supplying its wants. Thus Restoratives may remain in the system, and are intended so to do; but these may not remain. They must pass out. In so doing they come under the head of Eliminatives, or that of Astringents. This is their secondary action, distinct from their primary and most important operation. What then is the curative action of these remedies?

A large class of diseases depends on the presence in the blood of a morbid material, or, what amounts to the same thing, on the constant working of a morbid process in that fluid. Some of these, as the eruptive fevers, will run a certain course, and then come to an end. These we cannot generally stop, but can only alleviate. But others, more in number, and more commonly met with, tend naturally to run on for an indefinite period, unless by any means we can arrest their progress. Some depend on a contagious virus, communicable from one person to another, as Syphilis. Some, as Ague, are dependent on atmospheric or terrestrial influences. Others are due to some derangement of the secondary assimilative processes, as Scrofula, Scurvy, Gout, and Rheumatism. Others again, to causes that are ill understood, as convulsive disorders and skin diseases. Lastly, some may be caused in many different ways, as common inflammatory fever.

Now the object in the treatment of such diseases is to obtain in each case some remedy, that shall be able to counteract this process, something that shall destroy the morbid influence at work, and thus restore health. Medicines that are used with this intention form the second division of Hæmatics, which I have named Catalytics (Catalytica,) from a Greek verb signifying to destroy or to unbind.

Now though I have a probable hypothesis to advance as to the action of some of these, I would not have this considered as more than hypothetical. I would not speak positively of the action of any one of them, any more than to say that each of them tends to neutralize one or more particular morbid poisons.

Some have tried to give a general explanation of their action, and have talked of it as if it were easily understood by their known properties. I am not of their opinion; and when I speak of Catalytics, I shall give my reasons for disagreeing with them. Now each Catalytic has peculiarities and affinities that distinguish it from all others. I have not thought that I could arrange them more truthfully than by subdividing them according to diseases which they tend to counteract. How inadequately is the action of Mercury and of Iodine expressed by calling them special stimulants, alteratives, or absorbents! Is it not better and more correct to say at once that Mercury is useful in checking inflammation in general, and in counteracting the poison of Syphilis in particular? and that Iodine is effective in secondary forms of the latter disorder, as well as in Scrofula?

These medicines, then, are specifics, in so far as they are particularly useful in certain disorders, and in those excel other remedies; but they are not, in the vulgar acceptation of that term, the only medicines which can be employed in such a disease, nor is their use to be restricted to it alone. I have already said that a Catalytic tends of itself to work out a peculiar process in the blood. For this reason their administration in health generally does harm. They have nothing in the blood corresponding to them; or if so, they are not introduced to supply its want. Thus they must eventually pass out of the body. Before doing so, some may act on the nerves. While so passing out, they may, as I have said, act either as Astringents or Eliminatives on the glands. Under these heads their secondary action will be subsequently considered.

Being thus foreign to the blood, Catalytics do not remain there to supply a want; but just long enough to counteract a morbid action, and are then excreted.

Such is the difference between Restorative and Catalytic medicines. Although so far as this their action is sufficiently distinct, yet some care is required in separating the remedies in one division from those in the other. Sometimes both kinds are used in the same disorder. For whenever the action of a morbid poison causes any derangement in the proportion of the normal constituents of the blood, a Restorative may become of use to supply this defect. Thus a cancerous or scrofulous condition may cause a deficiency in the red colouring matter of the blood, which may be supplied by Iron. When, as in Gout and Rheumatism, there is an excess of acid in the system, partly due to an absence of that basic matter which should be present to neutralize it, this may be restored by an alkaline remedy. In both of these cases a Restorative may be used in a disease which depends on a morbid agency. But other remedies, Catalytic in their action, are of more direct use in such disorders. They counteract the original poison, and striking at the root of the evil, instead of correcting the consequences, they are more likely to eradicate the disease.

Some medicines come under both heads, acting in different ways in different cases. Thus Potash may be a Restorative in Rheumatism, but a Catalytic in Scrofula.

The operation of some particular agents is rather obscure. I shall have to show how it seems to me that the vegetable acids may act as Restoratives in fevers; and also to explain why, of those medicines which are used in Intermittents, I have placed Quina among Restoratives, and Arsenic with Catalytics.

It may be remarked that the fact that Catalytic medicines produce of themselves distinct actions in the blood has proved a stumbling-block to the disciples of M. Hahnemann. For in some few cases their action may, to a certain extent, simulate the disease which they tend to cure, and has thus been confounded with it by this imaginative observer. This partial resemblance is probably due to the fact that both disease and remedy produce a series of changes in the same set of particles in the blood. If it were not so, the remedy could not meet the disease. It would be out of its province, as not acting at all in the same sphere. But that the actions are essentially different is sufficiently proved by the fact that they counteract each other. The remedy, moreover, is often of equal efficacy in other different disorders. It has been shown in