Читать книгу The Action of Medicines in the System - Frederick William Headland - Страница 11

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 the modus operandi of 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 little of 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 the Methodic Sect among 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 the Chair 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 called light which 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, for Salt, Sulphur, and Mercury, 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 at least 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 the endosmotic properties of these liquids, as ascertained by experiment. It does not seem to me that these ideas can be successfully maintained. (Vide Prop. 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 be hot, cold, moist, or dry. There were four degrees of each of these properties. In the Pharmacopæia Londinensis of 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 were hot or cold, 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 a hot disease by a cold remedy.

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 their Philosophers' stone they could purify and rekindle the perishable base metal of 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 this Elixir Vitæ was 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, and Mercury. 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 of acid or alkalic 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 of fermentations in the blood which took place in the neighbourhood of the glandular organs. (Vide Eliminatives.) 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 them Hæmatolytica Physoda; and alkalies prevent the coagulation of the fibrine of the plasma, for which reason he calls them Hæmatolytica 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 can hardly 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 on vital or general principles. By vital I mean that these theories concern actions which could only take place in the living body. They may be termed general principles, because the grounds on which they are based are neither mechanical nor chemical, but something different from both. The term dynamical has 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 supposed that the general operation of remedies in the cure of disease is conducted in these various ways.

a. By degrees of stimulation.

b. By counter-stimulation.

c. By opposition.

d. By similar agencies.

e. By elimination.

f. By alterative actions.

g. By various counteractions.

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 inculcated by 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 that the 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. Thomas Sydenham, 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 a disease was 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 for specific medicines, 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 the aphorisms of 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 an alterative or revulsive action, by producing a distinct effect which diverted the attention of the system from the disease. His followers have classed remedies under three heads—as Stimulants, Debilitants, and Revulsives. He maintained also some other peculiar ideas.

Blood-medicines are commonly termed Alteratives, from the notion that they divert or alter the original disease by setting up in the system a peculiar process of their own. The term Revulsive is 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 into Biolytics, tending to dissolve life and structure; Anabiotics, which tend to stimulate the same; and Agonistics, tending to produce a "defensive" process, and acting by revulsion. Each class is again divided into those 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.

Schultz's Classification.
A. Biolytica. (Depressents.)
1. Plastilytica. (Mercury, Alteratives.)
2. Hæmatolytica. (Acids, Alkalies.)
3. Neurolytica. (Sedatives.)
B. Anabiotica. (Excitants.)
1. Plastibiotica. (Astringents.)
2. Hæmatobiotica. (Diffusible stimulants.)
3. Neurobiotica. (Opium, Strychnia.)
C. Agonistica. (Revulsives.)
1. Plastagonistica. (Purgatives, etc.)
2. Hæmatagonistica. (Irritants.)
3. Neuragonistica. (Emetics, Expectorants.)

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 in destroying organization, 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 the modus operandi of 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 are various different ways in which medicines may counteract, and thus cure, different diseases. This counteraction is distinct from contrary 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 on Mechanical or on Chemical principles, we are led to infer that their influence must for the most part be vital in 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 the modus operandi of medicines in the cure of diseases, is to say that they operate by various counteractions.

This, then, introduces my Third Chapter.