Dr. Pereira makes four orders ofCerebro-spinals; three include different kinds of Narcotics, very minutely subdivided; another is calledCinetics. They affect the muscular system; but it is altogether an assumption to assert that these medicines, Astringents and Tonics, do so by influencing the nerves. As to Astringents, it appears that they do not affect the nerves in any way, for which reason I shall have to make a separate class of them. For Tonics, there is great reason to suppose that in the first place they act on the blood; so that I cannot agree with Dr. Pereira, who ranks them amongNeurotics. Emetics are classed by him amongEccritics; but it seems to me that their action is either external, and of an irritant nature, or when from the blood, that it is exerted upon the nerves of the stomach. The stomach is not, like most glandular organs, a simple emunctory, and it is affected by medicines in a different way. Whereas gland-medicines increase secretion, the chief action of Emetics is to cause an evacuation of the contents of the stomach by contraction of itself and of other muscles. All substances which touch the stomach cause the copious outpouring of a thin fluid by mere contact; yet we cannot for this reason call them medicines which tend to increase secretion. Emetics acting from the blood after absorption, as Tartar emetic, which generally influence at the same time either the lungs or the heart, parts supplied by the other branches of the Vagus nerve, which isdistributed to the stomach, seem to me to be Specific Neurotics, probably acting on that nerve. So that in these points, as well as in some others, I am disposed to differ from Dr. Pereira.
It is apparent that in none of the classifications of this second kind is any mention made of the primary action ormodus operandiof medicines in the cure of disease, as a necessary basis of such distinctions.
In this third division are included those writers who have attempted to account for the mode in which medicines produce each their peculiar effects after entering into the blood, and some who have classified them according to their ideas on this point. It is with such theories as these that I am more immediately concerned in this Essay. Such writers have dived into a deeper subject than those who have directed attention to the general effects or tendencies of medicines rather than to the means by which such results are attained. Thus it is not to be wondered at that they have sometimes failed. Those have erred most who have allowed their imaginations to lead them astray from facts, or to guide them in matters which are naturally incomprehensible, to which our reason gives us no clue.
Attempts have been made to account for themodus operandiof therapeutic agents generally, in three different ways.
1. On mechanical principles.
2. On chemical principles.
3. On general or vital principles.
1. Mechanical theories of the action of medicines were greatly in vogue during the seventeenth and eighteenth centuries. There is a tendency in the human mind to explain every thing; and it was only natural for men who knew littleof chemistry or of physiology to resort to the science of physics, which they could comprehend, in attempting the explanation of observed phenomena.
John Locke, in his essay concerning the Human Understanding, published in 1689, gave it as his opinion, that the shapes of the minute particles of medicines were sufficient to account for their several operations.
"Did we know," said he, "the mechanical affections of the particles of rhubarb, hemlock, opium, and a man, as a watchmaker does those of a watch, whereby it performs its operations, and of a file, which, by rubbing on them, will alter the figure of any of the wheels, we should be able to tell beforehand that rhubarb will purge, hemlock kill, and opium make a man sleep." This idea did not originate with the great metaphysician. The first rudiments are to be found in the doctrines of theMethodic Sectamong the Romans, a medical branch of the Epicurean school. They held that diseases depended either on constriction or relaxation of the tissues, and that medicines operated by mechanically affecting these conditions.
The simple and philosophical statement of Locke was not improved by the various applications which were subsequently made of it. At the early part of the eighteenth century these ideas derived great support from the principles inculcated by Dr. Herman Boerhaave, the learned physician of Leyden. He likewise supposed that many diseases of the solid parts were to be attributed to a weakness or laxity of the animal fibres, and were to be cured by external or internal agents, which should act mechanically on those fibres so as to increase their tenacity. Also, that disorders of the fluids often depended on their being too viscid, and that this condition might be improved by agents which should attenuate this viscidity. Dr. Archibald Pitcairn, a Scotchman, the immediate predecessor and contemporary of Boerhaave, was elected to theChair of Physic in Leyden in 1691, and was also an able exponent of the mathematical theories. But he applied to physiology those ideas which were employed by the other to throw light upon physic; if that may be calledlightwhich was at least an improvement on the ignorance which preceded it.[8]He explained the digestive process by the mechanical trituration to which the food was subjected in the stomach; and accounted for secretion by supposing the existence in glands of vascular pores of different sizes, which intercepted certain particles of the blood; actually giving for the process a mathematical formula. He was a vehement opponent of those who based their theories on the then youthful science of chemistry, who, having scarce yet shaken off from them the dust of alchemy, only substituting Acids, Alkalies, and Fermentations, forSalt,Sulphur, andMercury, fell easy victims to his satire.
Dr. Charles Perry, in 1741, propounded a mechanical view of the action of Mercury and Arsenic. He thought that the particles of the former, being round and heavy, were able, when shaken about in the vessels, to break up and to annihilate those crude acrid humours which were the causes of disease; and that Arsenic acted as an irritant by the sharp and pointed nature of its atoms. He attributed the occasional poisonous effects of Mercury to the presence of Arsenic or some such substance as an impurity.[9]
Dr. Mead, in 1751, states that the administration of Mercury is dangerous in cases where there is carious bone, as there is a fear that its ponderous particles may break the weak lamellæ.[10]He was the Court Physician in the reign of George II. He accounted for the poisonous nature of the venom of serpents by asserting that it consisted of pointed particles, which pierced and destroyed the globules of the blood.
Dr. Perry conceived that some medicines, such as Steel and Antimony, did not act by their mere bodily presence, but by certain subtle vapours which emanated from them, and affected the vital spirits. This was a very misty notion. He stated that he borrowed this idea from a great philosopher of the German nation. This was probably Boerhaave, who lectured at Leyden in 1707.
Among those who regarded with favour the mechanical hypothesis, were Fourcroy and Hecquet in France, Van Swieten and Huygens in Holland, and Bellini in Italy. Excepting perhaps the case of external irritants, these explanations of the action of medicines have been universally condemned by scientific men at the present day. Doubtless these old authors were in the wrong, both in applying one hypothesis to the action of all remedial agents alike, and still more, in carrying their theories into such minute details, where it is impossible that they should be verified. And yet we may go too far in our condemnation of all such ideas. It does not seem to me to be so impossible, or even improbable, that the operation of some medicinal agents, particularly those which act on the nerves, may depend in some way on the shapes of the atoms of these substances, as related to those of the tissues which they influence. At least, there is no other possible explanation of the power of such substances. We know that the nerves are very much under the influence of mechanical impressions, upon which depend the phenomena of two atleast out of the five senses, those of hearing and touch, as probably also of the other three, if we understood them better. We know also that if we accept the Atomic theory, by which so many chemical phenomena are cleared up and explained, we must admit a certain definite and peculiar arrangement and shape to the ultimate particles of every compound body. These considerations render it possible that the ultimate particles of a stimulant medicine may be of such a nature as to irritate, or to refuse to coincide with, the ultimate molecules of the sensitive nerve with which they come in contact; and those of a sedative may, on the other hand, be so shaped and arranged as to dove-tail with those particles, and by extinguishing, as it were, their salient points, to cloak their vital sensibility. This is obviously a mere conjecture, and the only value which can attach to it is, that it appears in some sort to explain a thing which without it is inexplicable.
Some modern writers have attempted to clear up the actions of certain medicines by their supposed influence on the physical process of endosmosis, as carried on through the coats of the stomach and intestines. Poissenille and Matteucci have attempted to prove that the action of saline liquids in causing purging, and that of a solution of morphia in preventing the same, may be explained by theendosmoticproperties of these liquids, as ascertained by experiment. It does not seem to me that these ideas can be successfully maintained. (VideProp. II.)
2. Several attempts have been made to explain the general action of medicines on chemical principles.
Perhaps the strange doctrine taught by Galen, which prevailed for so many centuries afterwards, should be mentioned under this head as the first approach to a chemical theory. He considered all medicines to behot,cold,moist, ordry. There were four degrees of each of these properties. In thePharmacopæia Londinensisof 1702, translated by Dr. Salmon,it is stated of every herb that it possesses in a certain degree one or more of these qualities. It is amusing to find Dr. Salmon in great doubt as to whether Opium werehotorcold, as the Ancients said one thing, and the Moderns another. Galen supposed that diseases depended on similar qualities, and were to be counteracted by medicines; that, for example, we were to meet ahotdisease by acoldremedy.
The next advance, if such it may be termed, was made by the Alchemists of the middle ages, who frequently turned their attention towards the healing art, and almost imagined that by theirPhilosophers' stonethey could purify and rekindle the perishablebase metalof the human body. One of their dreams was, that from Gold, the most durable of metals, or from Mercury, the most lively and volatile, they might by their magical arts be enabled to prepare a medicine that should render life perennial. A most impracticable formula for the preparation of thisElixir Vitæwas given, among others, by Carolus Musitanus. Basil Valentine, who flourished in the fifteenth century, did good service by adding to the Materia Medica the preparations of Antimony, as well as the Mineral Acids. In the sixteenth lived Paracelsus and Von Helmont, the latest and most enthusiastic of the medical Alchemists. They considered the chemical principles of medicines, by virtue of which they operated, to be three in number,—viz.,Salt,Sulphur, andMercury. And though the seventeenth century was illumined by the philosophy of Bacon, and the discoveries of Newton and Boyle, we find that this strange doctrine survived in full vigour at the commencement of the eighteenth. It is laid down as an axiom in Dr. Salmon's Pharmacopæia in 1702.[11]
About the middle of this century there arose a new sect of chemical philosophers, somewhat better informed than the last. They imagined that most diseases depended on the predominance in the blood ofacidoralkalic humours, and that each of these conditions should be counteracted by a direct chemical antidote. They supposed also that the various secretions were the products offermentationsin the blood which took place in the neighbourhood of the glandular organs. (VideEliminatives.) In some of their ideas there was much that was reasonable; but it must be confessed that they were rather imaginative than argumentative, and, knowing really but little of the principles of that science on which their system was ostensibly based, they were ill-qualified to contend with their opponents of the mathematical school, who at least understood their own position. Foremost among these new chemical philosophers was Raymond Vieussens, who was severely censured by Dr. Pitcairn for having asserted that he had found an acid in human blood.[12]Vieussens was one of the earliest of the sect, which afterwards numbered many followers.
There is very little that is tangible to be discovered in these old chemical theories of the action of medicines; and it is not to be wondered at that most of them have faded away before the advance of science, and particularly before that wonderful development of the science of chemistry, which has distinguished the end of the last, and the first half of the present century.
We have seen that some of the early writers made great account of the affinities of acids and alkalies. So also a chemical explanation of the action of these remedies is generally adopted by writers at the present day. It is known that they have powerful tendencies to combine with each other, and it is supposed that these affinities are manifested even in the living blood.
Schultz attempts a further chemical explanation of their action in some diseases, particularly inflammations. He says that both affect the condition of the blood; but that acids tend to dissolve and destroy the corpuscles, wherefore he terms themHæmatolytica Physoda; and alkalies prevent the coagulation of the fibrine of the plasma, for which reason he calls themHæmatolytica Plasmatoda.
Some modern writers have tried to extend a chemical theory to the operation of medicines in general. This is an error to which those who have devoted themselves particularly to the study of chemical phenomena are especially prone.
Müller thinks that the agency of many remedies may be explained by their chemical affinities. He supposes that they may effect a change in the nutritive fluids, or that they may so disturb the state of combination in which the elements of an organ may be, that it becomes insensible to the action of morbid stimuli. Some chemists have accounted for the action of Alcohol by its chemical affinity for the brain substance. Liebig considers that the similarity of their composition to that of the brain may serve to explain the operation of such medicines as Quina and Morphia. Such ideas as these are at the best purely hypothetical, and even as theories they seem to me to be untenable,—for what reasons I shall have to show when I consider these remedies. Liebig has hazarded several other explanations of a similar kind, of which the following is an example:—"The frightful effects of Sulphuretted Hydrogen and Hydrocyanic Acid are explained by the well-known action of these compounds on those of Iron, when Alkalies are present, and free Alkali is never absent in the blood." (Organic Chemistry, p. 274.) Now in the first place it is not proved that the complete abstraction of iron from the blood would occasion sudden death, though doubtless it is a necessary constituent of that fluid. Further, Prussic Acid acts on the superficial nerves as an Anodyne when applied externally, which it canhardly do by displacing iron. Besides, by parity of reasoning, Ammonia, or Benzoic or Cinnamic Acid, should precipitate iron, if present in the blood in the soluble state, and Sulphuric or Nitric Acid should dissolve it, if in the state of peroxide; and yet none of these agents are frightful poisons. It is not to be imagined that chemical solutions and decompositions of every kind are allowed to take effect in the human system in the same way as in the laboratory of the chemist, for there are in the former many disturbing and controlling causes which suffice to hold them in check.
We may altogether conclude, that though the actions of many remedies may be partly elucidated by chemical considerations, it is impossible to account for the influence of all alike in this way. For at least the actions of nerve-medicines and of gland-medicines cannot be reasonably explained on any such hypothesis.
3. The most plausible explanations of the mode of operation of medicines have been founded onvitalorgeneralprinciples. ByvitalI mean that these theories concern actions which could only take place in the living body. They may be termedgeneralprinciples, because the grounds on which they are based are neither mechanical nor chemical, but something different from both. The termdynamicalhas sometimes been applied to an ill-understood vital action of this sort.
Many different ideas have been broached to account thus for the action of medicines. Some, who have constructed very ingenious and plausible systems, have explained in different ways the operations of different groups of medicines. But when others have adopted a single inflexible hypothesis to account for the action of all alike, this is found, as might be supposed, to be of a very untenable character. I will now consider very briefly several such ideas; first, for the sake of clearness, dividing them into seven sections. I shall explain my meaning as I proceed. Different writers have supposedthat the general operation of remedies in the cure of disease is conducted in these various ways.
a.This idea has received the title of the "Brunonian Theory," from the name of its founder. It was promulgated by the famous Dr. John Brown at the close of the last century. He considered all diseases to arise from excessive or diminished "excitement." He was of opinion that all medicinal agents were stimulants, only that some acted so powerfully as to produce "indirect debility." These latter were to be used in sthenic, the others in asthenic disorders. But it is to be urged against this idea, that many sedatives produce no appreciable degree of "primary stimulation;" that alterative medicines are neither stimulant nor depressent; and that the actions of different therapeutic agents,—as, for example, of Opium, Mercury, and Rhubarb,—differ very much in quality, and not simply in degree, as Dr. Brown supposed. The principle, then, cannot be maintained.
b.Rasori and other Italians adopted a similar idea about the commencement of this century, only that they supposed two contrary agencies, instead of variations in the degree of the same action, like the Brunonians. Giacomini classified medicines on this plan. The two classes of medicines are termed "Hypersthenics," and "Hyposthenics,"—i. e.Stimulants, and Contra-stimulants, or Sedatives. These were to be used respectively in asthenic and in sthenic disorders. But this idea did not originate with these physicians. It prevails among the modern Hindoos, and seems to have been inculcatedby certain medical writers of that nation in very remote times. (On the Hindoo System of Medicine, by Dr. Wise, 1845, p. 213.)
c.The last-mentioned idea supposes only one kind of opposition, and therefore only two descriptions of diseased action. But a much more plausible notion than that is, that each particular disease or symptom is to be cured by administering a remedy which is capable of producing a contrary state. By this contrary condition the disorder is to be neutralized. This was the maxim of Hippocrates—τα εναντια των εναντιων εστιν ιηματα—"contraries are the remedies of contraries." (De Flatibus, par. iii.) On this principle we give purgatives in constipation, opium in diarrhœa, sedatives to relieve pain, sudorifics to combat dryness of skin, etc. etc. But the rule becomes inapplicable when the cause of disease is so complicated that we cannot tell where to find a substance that shall directly oppose its agency. Besides, it cannot in theory be universally applied, for it takes no notice of treatment by evacuation or by revulsion.
d.I am brought now to an idea which is directly opposed to the last. The rule of the disciples of Hahnemann is, "Similia similibus curantur"—or, diseases are to be cured by remedies which shall produce effects similar to them. Now if this were the case, the majority of disorders would be hopelessly incurable. We know of no medicines that are capable of producing such affections as ague, small-pox, or phthisis; and when such remedies are known, their employment would certainly be singularly objectionable. Who would administer Strychnia in tetanus, Opium in congestion of the brain, or irritants in Gastrodynia? The arguments alleged in support of the theory are of the most fallacious kind. For example, it is said that diaphoretics cured the sweating-sickness, and purgatives are given with advantage in diarrhœa, on the "Homœopathic" principle. But it should be observed thatthe sweating in one case, and diarrhœa in the other, are the attempts of nature to get rid of the disease by eliminating a poison; and that in seconding these attempts we are availing ourselves of an agency which does not resemble the disease, but is like to the natural mode of cure. Such treatment depends, in fact, upon the principle which will have to be considered next in order.
The homœopathists would work a strange revolution in the Materia Medica.[13]Charcoal, Silica, and other substances commonly supposed to be inert, appear as remedies of wonderful efficacy. It is said that Belladonna produces a state like scarlatina, and also a condition resembling hydrophobia, and thus cures both of these disorders. Of these three propositions it is almost needless to say that all are equally erroneous. Further, an experimental trial of this principle was made by Andral on a large number of patients at the Académie in Paris, with the assistance of the homœopathists themselves. The medicines were carefully and fairly administered, but in no one instance were they successful. (Medical Gazette, vol. xv. p. 922.)
e.The idea that diseases are to be cured by assisting nature to eliminate from the system the morbid material, is probably as old as medicine. It was one of the doctrines of Hippocrates; but long even before his time it appears to have been inculcated by a certain sect of old medical writers among the Hindoos. These last were the very earliest advocates of the humoral pathology. (Dr. Wise,op. cit.p. 212.) Dr. ThomasSydenham, born in 1624, the contemporary of Harvey, and the most illustrious of the early English exponents of the humoral system, was probably the first in this country who clearly elaborated this view of the action of medicines by elimination; which has been more or less approved, though not so universally applied, by all who have lived since his time. Agreeing with Stahl in his view of the advantages of the "expectant" treatment of diseases, he thought it better to rely on the "vis medicatrix naturæ," than to make rash or violent attempts at a cure. He maintained that what we call adiseasewas in fact "no more than a vigorous effort of nature to throw off the morbific matter, and thus recover the patient."[14]He proposed, therefore, that our efforts should be directed to assist nature to procure the evacuation of a poison, promoting its elimination by acting on the various secretions—as by purgatives, diaphoretics and such medicines. For he had noticed that in fevers and febrile disorders the crisis or turning-point was generally accompanied or preceded by an increase in one or more of these secretions, and he regarded this as an indication of the treatment to be pursued in all such cases. "That," said he, "appears to be the best method of curing acute diseases, which, after nature has pitched upon a certain kind of evacuation, assists her in promoting it, and so necessarily contributes to cure the distemper."[15]He further proposed, that in the treatment of chronic diseases, when nature herself was slow in procuring this evacuation, we should seek forspecificmedicines, by which we might assist her in doing so, and thus effectually expel the morbific matter. This theory was reasonable and natural compared to those that followed it; but it was nearly extinguished and forgotten amid the war of opinions which was subsequently kindled by theaphorismsof Boerhaave. About this time we find Dr. Pitcairn mixing up this idea with his mechanical notions, in a treatise "On the Cure of Fevers by Evacuation." Huxham also, in 1729, maintained similar principles.
At the present day a more enlarged view is adopted. It is admitted that we may often assist these attempts of nature at a cure, and do good by the use, when thus needed, of evacuant medicines; but at the same time we must allow that there are many other advantageous modes of treatment,—that we may sometimes cut short a disease in the blood, or relieve a disorder by controlling vascular or nervous excitement, without resorting to elimination at all.
f.M. Broussais was one of the first who rightly maintained that many medicines were of use by means of analterativeorrevulsiveaction, by producing a distinct effect which diverted the attention of the system from the disease. His followers have classed remedies under three heads,—asStimulants,Debilitants, andRevulsives. He maintained also some other peculiar ideas.
Blood-medicines are commonly termedAlteratives, from the notion that they divert or alter the original disease by setting up in the system a peculiar process of their own. The termRevulsiveis especially applied to medicines which produce a powerful local effect, and are supposed so to occupy the attention of the system as to tend to cure the disease which formerly engaged it. Counter-irritants externally, and emetics among internal medicines, are generally admitted as revulsives.
The idea of revulsion is a prominent feature in the arrangement of medicines adopted by Dr. Schultz, of Berlin, who adds to the above, Expectorants, Purgatives, Diuretics, and Sudorifics. He divides medicines intoBiolytics, tending to dissolve life and structure;Anabiotics, which tend to stimulate the same; andAgonistics, tending to produce a "defensive" process, and acting by revulsion. Each class is again divided intothose which affect the organs and nutrition in general; those which act on the blood; and those which particularly influence the nerves. I will give examples of each.
These divisions are again subdivided with great minuteness, according to their supposed operation. And yet it will be seen that, in spite of the hard names, there is an admirable simplicity in this arrangement. So many and so various are the statements made, and so plausible the theories involved, that I cannot accord to it here a fair consideration. I must object to it, however, that there is too much generalization, and, what is more important, that many medicines may cure diseases without necessarily causing either excitation or depression or acting distinctly by revulsion. The only principles of action admitted here are these three, the same which are adopted by the disciples of Broussais. To suppose that medicines acting on the glands are only of use as revulsives, that they have no influence on the blood, and are never engaged in purging the system of peccant or morbid matter, is surely incorrect in theory. Medicines of the first class, when given in proper dose and in fit cases, are not engaged indestroyingorganization, nor is it invariably the case that such remedies as Mercury, Acids, and Alkalies act even as depressents, when given in moderation.
Further, the lines of distinction are too arbitrary, and drawn with too much precision. The variations in the actions of different medicines are too many and too great to be thus easily accounted for, and we do not know enough about many of them to be able to define their operation so exactly. And there is no explanation at all given here of the special tendencies of some remedies, by which we are enabled to cure a great number of disorders.
g.The Hippocratic maxim was a step towards a correct solution of the therapeutical operations of remedial agents. The humoral theory of Sydenham, and the threefold action supposed by Broussais, were further advances in the right direction. But these views were all too confined. Correct as far as they extended, they did not embrace the whole range of the subject; for it is impossible to explain by any one of them the operations of all medicines.
Biassed by the satisfactory observation which he had made of themodus operandiof particular medicines, and misled by the insufficiency of his knowledge, each of these writers was tempted to apply the view which was applicable to a certain set to all remedies alike. Once persuaded of its sufficiency, he easily found arguments by which to fortify both himself and others against any subsequent objections.
The right course lies in a combination of these various theories, embracing what is true and discarding what is erroneous in each of them, and supplying what may seem to be wanting in the whole. None of these ideas being by itself perfect, the sounder reasoners of the present day are driven to suppose that there arevariousdifferent ways in which medicines maycounteract, and thus cure, different diseases. Thiscounteractionis distinct fromcontrary action; it may be direct or indirect; and it allows of any action in a medicine, tending to restore health, except an effect similar to the disease. Such a view was adopted by Dr. Cullen, the well known Nosologist,who lectured at Edinburgh towards the close of the last century. He discarded all special and confined views of the operation of medicines, believing that they acted in many and various ways, all of which tended to the same end—to counteract the influence of the disorder. This is well exemplified in his admirable directions for the treatment of fever, in which he enjoined the use of a number of different remedies, varied according to the nature of the case, and progress of the symptoms.[16]
Dr. Pereira, the most learned and acute of living English writers on this subject, appears, like many others, to prefer a wide explanation of this description.
On such views my own statements are based. I suppose that a disease in the blood is to be met by agents in the blood, which directly or indirectly counteract it there; that disorders, generally temporary, which depend on nervous derangement, are to be benefited by remedies which affect the nerves; and in the same way that a laxity of muscular fibre, or a failure in a secretion, should be treated by agents which especially possess the property of restoring to a right condition such parts or functions.
Concluding, then, that it is impossible to account clearly for the actions of most medicines onMechanicalor onChemicalprinciples, we are led to infer that their influence must for the most part bevitalin its nature—that it must be such as could only be exerted in the living body. Even then we are unable to fix upon any single rule or formula which shall be capable of accounting for the actions of all at once. So it seems that the only general explanation which we can offer of themodus operandiof medicines in the cure of diseases, is to say that they operate byvarious counteractions.
This, then, introduces my Third Chapter.
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.
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 byinternal 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 surfaceis 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 notnecessary, 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 fortioriwould 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 notthe 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 ofpossibility, 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 Imean 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 byCounter-irritationorRevulsion, 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. (VideProp. 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 calledShock. 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 ofmedicines, 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.
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 ofAbsorptionandEndosmosishave 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; wehave 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 DutrochetEndosmoseandExosmose, 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 whichhas 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 sidepromotes 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, thatany pressure on the fluid on one side of the membranehas 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 theLectures 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 lessspecific 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:—