The Action of Medicines in the System. Frederick William Headland
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:—