The Action of Medicines in the System

In commencing this Essay on the Action of Medicines, I must confess that I feel at first a certain discomfort when I consider the magnitude of the task before me. Many a volume has been written to elucidate the operations of single medicines, and when the variety and complexity of such an operation is considered, the space devoted to its consideration will hardly seem too great. Thus it is not to be wondered at that, when pausing on the threshold of my subject, I should be sensible of the many difficulties with which such an inquiry is surrounded.

In this introductory chapter it will be my aim, in the first place, to set forth briefly the great importance and extent of the subject, showing that it is an essential requisite in the advance and perfection of medical science. Next, I must insist on the advantage of correctness and clearness of language and argument in the treatment of such topics as this, and show in what manner I propose myself to attain to it. And in the third place, I must shortly explain the scheme or arrangement which will be followed in this Essay. If the preliminary remarks contained in this chapter are not first considered and clearly apprehended, I fear that I may be but imperfectly understood in what I shall have to say hereafter.

There have been, more or less, in all ages, two systems or schools of medical treatment, of which the one prevails among ignorant men, and in rude states of society, but the other requires a higher degree of enlightenment. These are the Empirical and the Rational systems. The first is founded on simple induction. By accident or by experience it is found that a certain medicine is of use in the treatment of a certain disorder: it is henceforth administered in that disorder; and on a number of such separate data an empirical system is constructed. It naturally requires for its elaboration a comparatively small degree of knowledge.

Now this observation of facts is indispensable as a beginning, but something more is required. We must not be satisfied with taking them separately, but we must proceed to compare together a large number of facts, and draw inferences from this comparison. And our plan of treatment will become rational, when on the one hand, from an accurate knowledge of the symptoms of diseases, we are better enabled to meet each by its appropriate remedy, and on the other hand, from some acquaintance with the general action of a medicine, we are fitted to wield it with more skill and effect, and to apply it even in cases where it has not yet been proved beneficial. Thus, for the proper perfection of medicine as a rational science, two things are in the main needed: the first is a right understanding of the causes and symptoms of disease; the second, a correct knowledge of the action of medicines. Should our acquaintance with these two subjects be complete, we should then be able to do all that man could by any possibility effect in the alleviation of human suffering. This sublime problem is already being unravelled at one end. Diagnosis and Nosology are making rapid strides; and perhaps we shall soon know what we have to cure. But at the other end our medical system is in a less satisfactory condition; and though some impatient men have essayed, as it were, to cut the Gordian knot, and have declared boldly on subjects of which they are ignorant, yet it must be confessed, that in the understanding of the action of medicines, and of their agency in the cure of diseases, we do not so much excel our ancestors. While other sciences are moving, and other inquiries progressing fast, this subject, so momentous in its applications, has, in spite of the earnest labours of a few talented investigators, made after all but small progress. Let but those who feel this want bestir themselves to remove it, and it will soon be done. Those doubts and difficulties, which are now slowly clearing away before the efforts of a few, will then be finally dispelled by the united energies of all; and instead of our present indecision and uncertainty on many points, we shall find ourselves eminently qualified to wage the conflict with disease, being skilled in that science whose name bespeaks its peculiar importance, the science of Therapeutics.

The subject assigned to me as the text of this Essay concerns this problem:-"On the mode in which Therapeutic Agents introduced into the stomach produce their peculiar effects on the Animal Economy." It is naturally a subject of very great extent; and one difficulty with which I am beset is that I scarcely know how to compress what I have to say on the action of medicines into the compass required. It will be granted that it is an important subject; it is also a difficult one. This difficulty depends mainly on the variety and complexity of the proof required to establish any one point with absolute certainty.[1] A long time ago, when men knew and understood less than they do now, it was fancied that the action and choice of medicines was a thing of the utmost simplicity; that it was comparatively an easy matter to fix at once upon that remedy required most in any particular case.[2] But the light of science, which in this day burns more brightly, at the same time that it displays all objects with greater distinctness, discloses to us also many dim vast tracts in the distance, of which nothing had been seen or imagined before. In this, as in other things, the more we know the more we discover our real ignorance. It is wrong, then, to treat dogmatically of matters that we cannot comprehend; and when perfectly in the dark as to the operation of a medicine, we should rest content with declaring the result of that operation. This by itself will be of great use to us.[3]

I am induced to lay stress on the difficulties surrounding an inquiry into the modus operandi of medicines, because it will be some excuse for the manifest insufficiency of the sketch which I am about to draw. For this, too, I may find a further apology in the fallacies and mistakes, both of reasoning and statement, of which previous writers have been guilty. These are best shown by their discrepancies. On no question, perhaps, have scientific men differed more than on the theory of the action of medicines. Either facts essentially opposed and incompatible have been adduced by the disagreeing parties; or, which is nearly as common, the same fact has received two distinct and opposite interpretations. Many hypotheses, when tested, are seen to be grounded on bare assertions, and to be destitute of logical proof; many others are attempted to be established on ill-sustained analogies. Analogy, in such a case as this, may be used to increase a probability already evidenced; but by itself it is no proof, for we find often that medicines are capable of producing the same result in very dissimilar ways.

How then are we to arrive at the truth! The best and surest way is to be extremely careful in the means which we employ in its discovery.

It is, I think, impossible to overrate the importance of exact precision of language and thought in scientific details, and in the deduction of conclusions from them.[4] A subject so interesting as this requires to be treated in a logical way. Facts, when ascertained, should be ranged together and compared, and exact inferences made, without ever straining a point. And when we are inclined to hazard a theory that is barely supported, we should take care to state it as a theory, and not to bring it forward as a truth. It has not been an uncommon habit among scientific authors, who should be of all men the most careful and exact, to confound assertion with fact-to mistake hypothesis for truth. In such illogical and incorrect reasoning is to be found the true source of a multitude of errors.

Being sensible of this danger, I have endeavoured to keep it in view in the arrangement of this Essay. In order to obtain, if possible, this clearness and precision, or at all events, to be better understood, I have arranged the heads of my ideas on the action of medicines in a number of distinct propositions, the scope of which will be presently described. I shall attempt to prove each of them separately, as if it were a theorem in geometry, sometimes dividing it first into a number of minor propositions, which, taken together, imply the original one, and which have to be severally discussed.

The great use of such an arrangement is its distinctness: so that it may in any case be easily seen whether a proposition has been established, or whether I have failed to prove it. These propositions are the foundation of the Essay; and upon them has been erected a superstructure of more or less logical consistency. In them has been stated about as much of the general principles by which medicines operate as seems to me to be capable of distinct proof: i.e. which may be regarded with that kind of certainty which we generally expect to attain to in scientific matters. So far, then, I have kept myself in a straight road, between two walls, diverging neither to the right nor to the left to gratify my inclination; it being, as I have said, a most obvious duty to guard against stating that for fact which is at the best uncertain. But having gone so far, I have in several instances indulged in speculations and hypotheses on certain matters, taking care to state that such explanations are only probable, and very far from determined. But it is often our duty to inquire into uncertain things; and those who do so, who officiate, in however humble a capacity, as the pioneers of knowledge, have to hazard many conjectures before they arrive at the truth. In striving after truth, we must investigate many an unknown path, and try at many a door where we have not before entered. Thus, when in some cases I have perceived before me a line of thought stretching onwards, and seeming to lead somewhere in the direction of truth, I have not, as it were, shunned it, or turned aside to tread only in more certain paths, but I have thought it my duty to follow it up, and to investigate it thoroughly, to see if by any means it might not help me on my way to that desired haven. These theories are the weak points of the Essay, but I must crave indulgence for them on the grounds alleged above. It will be observed that the original propositions are so stated, that the overthrow of any one of these extra hypotheses would not shake them, or in any way invalidate their proof.

I will now sketch out the arrangement which I propose to follow in the consideration of the topics which present themselves to me.

In the next chapter I shall take a brief review of the opinions of other writers on the subject of the action of medicines; knowing, indeed, that in so short a notice I shall be perfectly unable to do them justice, but wishing, in some broad points, to draw the line between what is known and what is unknown,-what is ascertained and what is debated,-what is approved and what condemned. In some cases also I may venture to object to opinions hitherto unquestioned. Now, as the best key to the main opinions of authors on this subject, we have to consider the various classifications of medicines which they have adopted. A classification of remedies presupposes a set of theories concerning either their primary action or their general results, and is, in fact, identical with them. The formation of such an arrangement depends on the necessity of considering medicines in groups, each possessed of some common character, in order that their various properties may be simplified, and admit of being compared.

In a classification we do not so much consider the peculiarities of single remedies, as the points in which large numbers agree together. These points of resemblance we gene rally find to be of the most importance. I have to consider three sets of authors in the second chapter. The first set treat of the general or ultimate effect of a medicine on the system; and classify medicines accordingly. A second set of writers have arranged therapeutical agents according to the organ or part of the body to which their action is especially directed. Neither of these deal with the mode in which medicines act as the basis of classification. A third set of writers have attempted in various ways to explain the modes of operation of medicines. They have laid down general rules about these operations, and have constructed more or less plausible theories on the subject. Some few have classified remedies on this plan. Now, with these theories I am more particularly concerned, as they trench immediately on the subject of this Essay. But they are not many, and it will not take us long to review them.

It is easier to find fault than to teach. After pointing out the shortcomings of some who have preceded me, I find myself necessitated in the third chapter to state my own conclusions as to the modus operandi of medicines.

Let us consider, as it were, the history of a remedy from the beginning to the end of its course. It is already "introduced into the stomach"-we must commence with it there. Now it does not remain there. It cannot act from the surface of the stomach through the medium of the nervous system.

In the First Proposition it is affirmed that it must obtain entry into the fluids of the body-pass, that is, from the intestinal canal into the system at large-before its action can begin. There are four proofs of this. It is shown that when introduced at another part of the body a medicine acts in the same way as when placed in the stomach. It is found by direct experiment that a poison will not act through the medium of nerves only, but that its passage in the blood is required. Thirdly, the course of the circulation is quick enough for the most rapid poison or medicine to pass quite round the body from the veins of the stomach before it begins to operate. The last and most conclusive argument to show that medicines pass out of the stomach into the system, is that they have actually been detected by chemists, not only in the blood, but in the secretions formed from the blood. Remedies, then, pass from the stomach into the blood and fluids. How do they do so?

In the Second Proposition it is laid down that all those which are soluble in water, or in the secretions of the stomach or intestines, pass through the coats of these organs into the interior of the capillary veins which surround them. It has already been shown that most medicines pass through in some way; we shall now have to learn how they pass, and what special arrangements are made for the passage of substances differing in nature. By the physical process of absorption a liquid may pass through the animal membranes, from the interior of the stomach or intestine to the interior of the small vein which lies close outside it. In examining the laws by which this process is conducted, we shall find that all the requirements are present in these parts, provided only that the substance to be absorbed shall be first in some way dissolved, and reduced to the liquid state. In the stomach there is, in contact with the substance just introduced, a thin watery secretion containing acid and a matter called pepsin: this is the gastric juice. A large number of medicines are soluble in water. They are dissolved in this fluid. Some others are soluble in dilute acid. These too are dissolved here. Albumen, and matters like it, are reduced to solution by the aid of the pepsin, which is the principle of digestion. But there are some few mineral bodies, and many vegetable substances, as fats and resins, which cannot be thus dissolved by the juice of the stomach. They are soluble, more or less, in a weak alkaline fluid; and such a fluid is the bile, which is poured out into the first portion of the intestine. They too are reduced to solution and absorbed. In this manner it is shown that a very great majority of remedial agents are capable of being reduced to solution, of being absorbed without material change, and of passing thus into the circulation.[5] Very few are quite insoluble; but some that are dissolved with difficulty may be left partly undissolved in the intestinal canal. What becomes of these?

It is asserted in the Third Proposition that substances which are thus insoluble cannot pass into the circulation. Arguing from a physical law, we should say at once that it was impossible; but the matter cannot be so lightly dismissed, for a foreign professor has lately asserted that insoluble matters may and do pass into the circulation. I have made experiments to satisfy myself on the point, and have come to the contrary conclusion.

In the Fourth Proposition it is stated that some few substances may act locally, by irritation or otherwise, on the mucous surface of the stomach or intestines. These are not many; they act without being absorbed; and they do not extend into the system at large. In some few cases, these local actions may be succeeded by changes in distant parts, on the principle of Revulsion.

Having just shown how medicinal substances are absorbed, we have now to suppose that they are in the blood.

It is next maintained, in the Fifth Proposition, that the medicine, being in the blood, must permeate the mass of the circulation as far as to reach the part on which it tends to act. This it can easily do. The circulating blood will conduct it any where, in a very short time. Supposing a medicine has to act on the liver, or on the brain, or on the kidney, it does not influence these organs at a distance, but it passes directly to them in the blood, and then its operation is manifested. This may be called the rule of local access. Its proof depends on two things: on the impossibility of the medicinal influence reaching the part in any other way, as shown in the first proposition; and on the fact of medicinal agents having been actually detected in many cases in the very organs over which they exert a special influence. But are there any exceptions to this? Can a medicine ever produce an effect without actually reaching the part? It seems that there may be two exceptions. In some cases an impression of pain may be transmitted along a nerve from one part to another; and in some other few instances a muscle, when caused to contract by the influence of a medicine, may cause other muscles near it to contract by sympathy.

Before we inquire into the remedial action of the medicine in the blood, we must consider whether that fluid may not first alter it in some way, so as to hinder or affect its operation. To a certain extent this is possible.

In the Sixth Proposition it is asserted that while in the blood the medicine may undergo change, which change may or may not affect its influence. It will have to be shown that this change may be one of combination, as of an acid with an alkali; of reconstruction, when the elements of a body are arranged in a different way, without a material change in its medical properties, as when benzoic is changed into hippuric acid; or of decomposition, when a substance is altogether altered or destroyed, as when the vegetable acids are oxidized into carbonic acid.

Having considered these preliminary matters, we shall arrive at the main point. The medicines are now in the blood. We must consider what becomes of them; what they do next; where they go next; and how they operate in the cure of diseases. I have made a classification in which medicines are divided according to my views of their mode of operation. The classes and their subdivisions will serve for references in illustration of what I have to say. For it is not possible to speak of the general operation of medicines without adducing particular instances; nor will time and space always allow me, in doing so, to refer to individual medicines.

There are four great groups of medicines, the action of each of which is well marked and distinct. The first class acts in the blood; and as a large number of diseases depends on a fault in that fluid, we may by their means be enabled to remedy that fault. They are the most important of all medicines. They are called H?matics, or blood-medicines. They are used chiefly in chronic and constitutional disorders. But a second class of remedies are temporary in their action. They influence the nervous system, exciting it, depressing it, or otherwise altering its tone. They are chiefly useful in the temporary emergencies of acute disorders. They can seldom effect a permanent cure, unless when the contingency in which they are administered is also of a temporary nature. They are called Neurotics, or nerve-medicines. A third set of medicines, less extensive and less important than the others, acts upon muscular fibre, which is caused by them to contract. Involuntary muscular fibre exists in the coats of small blood vessels, and in the ducts of glands. Thus Astringents, as these agents are called, are able, by contracting muscular fibre, and thus diminishing the calibre of these canals, to arrest hemorrhage in one case (when a small vessel is ruptured,) and to prevent the outpouring of a secretion in another case.

The fourth class is of considerable importance. Some medicines have the power of increasing the secretions which are formed from the blood by various glands at different parts of the body. By their aid we may be enabled to eliminate from the blood a morbid material through the glands; or we may do great good by restoring a secretion when unnaturally suppressed. They are called Eliminatives. Like H?matics, their influence is more or less permanent. That of Neurotics and Astringents, particularly the former, is transient.

The general mode of action of these four classes of therapeutic agents is laid down in the four remaining propositions, about as far as it seems to me to be capable of a positive definition. Each proposition concerns one of these classes of medicines. All I can do now is to recapitulate the chief affirmations made; as to give any idea of their proof would require me to enter into a number of details which had better be postponed to the third chapter.

In the Seventh Proposition it is stated of H?matic medicines that they act while in the blood, over which fluid they exert an influence; and that their effect, whatever it be, is of a more or less permanent character. A line of distinction is drawn between two divisions of this class of blood-medicines. Some of them are natural to the blood; they resemble or coincide with certain substances that exist in that fluid; so that, having entered it, they may remain there, and are not necessarily excreted again. These are useful when the blood is wanting in one or more of its natural constituents. This want causes a disease, and may be supplied by the medicine, which in this way tends to cure the disease. Medicines of this division are called Restoratives; for they restore what is wanting.

Some other blood-medicines, although they enter the blood, are not natural constituents of the vital fluid, and cannot remain there, for they are noxious and foreign to it. They must sooner or later be excreted from it by the glands. They are of use when disease depends on the presence and working in the blood of some morbid material or agency, which material or action they tend to counteract or destroy. They may be called vital antidotes; not strictly specifics, for they are not always efficacious, on account of variations in the animal poisons, or from the casual operation of disturbing causes. They are applicable in those many disorders which depend, not on the absence of a natural substance, but on the presence of an unnatural agent in the blood. These medicines are called Catalytics, from a Greek word which signifies to break up or to destroy. Having performed this, their function, they then pass out of the blood.

All this requires to be proved.

In the Eighth Proposition it is stated of Neurotics, or nerve-medicines, that they act by passing out of the blood to the nerves, which they influence. This is only to insist on the rule of local access, already laid down in Prop. V. It is further affirmed that they are transitory in action. They appear to effect molecular changes in nerve-fibre, similar to those by which the phenomena of the senses are produced, and which are by nature transitory in their results. And yet they may be very powerful, even so as to extinguish vital force. Thus, short and unenduring as is the operation of these agents, it may last long enough to cause death, and so a temporary influence produce a permanent result. There are three divisions of Neurotics. The first set are of use when there is a dangerous deficiency of vital action. These are Stimulants. They exalt nervous force, either of the whole nervous system, or only of a part of it. They vary very much in power. A second set, called Narcotics, first exalt nervous force, and then depress it. They have thus a double action; but they have also a peculiar influence over the functions of the brain, which is different from any possessed by other nerve-medicines. They control the intellectual part of the brain, as distinguished from its organic function; the powers of mind more than those of life. Some Narcotics tend to produce inebriation; others, sleep; others, again, delirium. In the third place some Neurotics tend simply and primarily to depress nervous force. They may act on the whole nervous system, or on a part of it only. They are often very powerful; and they are of use when, from any cause, some part of the nervous system is over-excited. They are called Sedatives. Like other Neurotics, they are used in medicine as temporary agents in temporary emergencies. If a permanent action be required, the remedy must be constantly administered, that the effect may be kept up by continual repetition.

In the Ninth Proposition it is affirmed of Astringent medicines that they act by passing out of the blood to muscular fibre, which by their contact they excite to contraction. They do not so much influence the voluntary fibre of the muscles, which is under the direct control of the nervous system: but they chiefly manifest their action on the involuntary or unstriped muscular fibre, which is not directly controlled by the brain and nerve-centres, and for this reason more under the operation of external or irritating agents. Meeting this in the coats of the capillary vessels and of the ducts of glands, they are enabled to act as styptics, and as checkers of secretion. The action of Astringents appears to depend on a chemical cause; for we find that all of them possess the power of coagulating albumen.

The Tenth Proposition treats of Eliminatives. It is not said simply that these increase the secretions of a gland; or that they stimulate the glands while passing by them in the blood. But it is laid down as a rule that they act by themselves passing out of the blood through the glands, and that while so doing they excite them to the performance of their natural function. They are substances which are unnatural to the blood, and must therefore pass out of it. In so doing they tend to pass by some glands rather than by others: in these secretions they may be detected chemically; and it is on these glands that they have an especial influence. Their uses in treatment are various and manifold.

In these classes are included all medicines that act after entry into the blood. On referring to the classification which precedes this chapter, it will be seen at a glance what groups of medicines are arranged as orders under each class or division.[6] In the third chapter I shall attempt at some length to prove the propositions which treat of these four classes; and I shall also attempt to explain the nature and mode of action of the orders, or small groups of remedies.

In the fourth chapter some of the more important medicines will be considered separately, either as individually interesting, or as illustrative of general modes of operation previously described.

I may point to some parts of the Essay as being more original than others, although not perhaps for that reason more valuable. For this purpose may be mentioned the treatment of the second proposition: the distinction attempted to be drawn between the two divisions of blood-medicines; the account given of Tonics in one of these divisions, and of Anti-arthritics in the other; the theory of the action of Eliminative medicines; and the experiments made on the action of Aconitina.

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