This section is from the book "A Treatise On Therapeutics, And Pharmacology Or Materia Medica Vol1", by George B. Wood. Also available from Amazon: Part 1 and Part 2.
It was at one time thought by many that medicines never entered the circulation. The absorbents were supposed to afford the only avenue of foreign bodies into the system. Substances incapable of being assimilated to the blood, were believed to penetrate no farther than the absorbent glands, which were so many sentinels placed to guard the system against the intrusion of noxious agents. This notion was purely theoretical; and, even at the time when it was most strenuously maintained, was opposed by known facts which prevented it's universal adoption. Subsequent experiments and observations, extremely numerous, and diversified in almost every conceivable manner, have established the conclusion, beyond all possible doubt or cavil, that medicines are very frequently absorbed, and, entering the blood-vessels, are circulated with the blood throughout the body. The following proofs of this truth may be adduced.
1. When medicines are applied directly to any surface of the body. and produce their characteristic effects elsewhere, it may often be noticed that portions of them have disappeared, without any possibility of accounting for their disappearance except by their absorption, or at least their entrance into the system.
2. The sensible properties of the medicine, its odour, taste, and colour, are frequently perceptible, either unchanged, or somewhat modified, in the breath, the secretions, and even in the various solid tissues. The effect of garlic in diffusing its odour and taste is universally known; rhubarb gives to the urine the property of staining linen yellow; and madder not unfrequently imparts its red colour to the bones.
3. The peculiar medicinal or poisonous effects of certain substances are occasionally produced, by taking into the stomach the liquid secretions of individuals under the influence of these substances. Thus, medicines given to the mother not unfrequently operate on the suckling; and numerous other illustrations of a similar kind might be adduced.
4. Effects, produced by medicines in distant parts, may be prevented by ligatures around the blood-vessels proceeding from the part with which the medicine is brought into immediate contact.
5. In many instances, the characteristic effects of medicines, exhibited in the ordinary way, may be obtained by injecting them into the bloodvessels.
6. But the most irresistible evidence is that afforded by chemical investigation, which has in almost innumerable instances detected medicinal substances taken into the stomach, or applied to other parts of the body, not only in the perspiration, saliva, urine, and other secretions, and in various solid tissues, but in the blood itself. Indeed, the list of substances, which have thus been proved to have been circulated through the system, is so large as to authorize the inference, that all medicines, capable of extending a direct action beyond the original surface of contact, may be absorbed, and carried with the blood to the part or organ which they affect.
It has been said that the effects of some medicines and poisons are so rapid, as to preclude the idea that they could have been absorbed, and conveyed to the seat of their action by the ordinary route of the circulation. But comparatively recent experiments, by proving the extreme rapidity with which the blood makes a complete circuit in the body, have invalidated that objection. Professor Hering, of Stuttgard, found that ferrocyanide of potassium, injected into the jugular vein of a horse, might be detected in the opposite jugular vein in a period of time varying from twenty to thirty seconds (Zeitschrift fur Physiohgie, iii. 122); and Dr. James Blake, formerly Professor of Anatomy in the Saint Louis University, has proved that "the time required for the blood to pass from the jugular vein, and to be circulated through the body, was, in the horse sixteen seconds, in the dog twelve seconds, in the fowl six seconds, and in the rabbit four seconds". (Am. Journ. Med. Sci. N. S., xviii. 100). The latter experimenter also found that the most rapidly fatal poisons, introduced into the veins of the animals referred to, gave rise to no signs of their action within less than the periods of time mentioned as occupied, in the several animals, by one round of the circulation. (Ibid., p. 101). Having introduced some hydrocyanic acid into the mouth of a rabbit, Dr. Blake noticed that its first effects on the system were evinced in two seconds and a half, and death followed in five seconds. (Ibid., p. 106). It is scarcely possible that any medicine can act more speedily than this; and, considering that the acid probably acted through the lungs, and, by entering the pulmonary veins, might reach the left side of the heart by a route much shorter than that of the general circulation, it is not too much to infer, that the time mentioned was sufficient for it to arrive at the brain through the medium of the blood. Vierordt, after experiments with a great number of animals of different species, came to the conclusion, that the mean duration of a round of the circulation in the several mammalia is equal to the average time in which the heart completes twenty-six or twenty-eight pulsations. (B. & F. Medico-chir. Rev., July, 1859, p. 167). It may be assumed that in man this time does not exceed thirty seconds. From these facts the inference may be fairly drawn, that no medicine acts with such rapidity as to preclude the possibility of its having reached the part affected through the circulation; and, the accuracy of the statements being admitted, the objection urged upon this ground against the universality of the mode of operation through the blood must be abandoned.
Medicines are absorbed from mucous membranes, the areolar tissue, the skin, the pulmonary air-cells, and probably from any other part of the body to which they may be applied. The rapidity of their absorption is proportionate to the thinness and delicacy of the tissue intervening between them and the blood-vessels. Hence, of all the surfaces with which they are habitually brought into contact, that of the pulmonary air-cells affords them the most speedy entrance into the circulation. Every one knows the great rapidity with which ether and chloroform act when inhaled. Next to the air-cells in this respect are probably the areolar tissue and the alimentary mucous membrane, especially that of the stomach, which, as a general rule, admits the entrance of medicines more readily than that of the rectum. Absorption takes place most slowly from the skin. This might be inferred from the firmness and thickness of the epidermis. It has indeed been maintained that this tissue is impermeable by medicines in its healthy state. But experiments have satisfactorily shown that they do enter the system through the epidermis; and the constitutional impression, sometimes resulting from the wearing of a mercurial plaster, is of itself a sufficient proof. There can be no doubt, however, that the epidermis opposes a great impediment to absorption; and, without such a protection, the system would be constantly exposed to the most deleterious influences from without. The impediment may be much diminished by softening the tissue with water, or by mechanically deranging it; and hence medicines applied to the surface by a local or general bath, or in the form of cataplasm, or by means of friction, may often be made to act efficiently on the system.* Deprived of its epidermis, the skin admits the entrance of medicines with great facility, though, even in this state, somewhat less readily than the gastric mucous membrane, probably because it is less vascular.