THE

ACTION OF MEDICINES

IN

THE SYSTEM;

OR,

"ON THE MODE IN WHICH THERAPEUTIC AGENTS INTRODUCED INTO THE STOMACH PRODUCE THEIR PECULIAR EFFECTS ON THE ANIMAL ECONOMY."

Being the Prize Essay

TO WHICH THE MEDICAL SOCIETY OF LONDON AWARDED THE FOTHERGILLIAN GOLD MEDAL FOR MDCCCLII.

BY

FREDERICK WILLIAM HEADLAND, B.A.,

M. R. C. S., ETC.

PHILADELPHIA: LINDSAY AND BLAKISTON.

1853.

WM. S. YOUNG PRINTER

TO

THE PRESIDENT, OFFICERS, AND FELLOWS

OF THE

MEDICAL SOCIETY OF LONDON,

This Essay

IS RESPECTFULLY INSCRIBED, BY THEIR VERY OBLIGED

FRIEND AND SERVANT,

THE AUTHOR.

[CONTENTS.]

A CLASSIFICATION OF MEDICINES WHICH ACT AFTER ENTERING INTO THE BLOOD, ACCORDING TO THEIR SUPPOSED MODES OF OPERATION.

[CHAPTER I.]

INTRODUCTORY REMARKS.

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 Hæmatics, 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 Hæmatics, 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 Hæmatic 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.

[CHAPTER II.]

ON SOME OF THE MORE IMPORTANT CLASSIFICATIONS OF MEDICINES, AND OPINIONS OF AUTHORS RESPECTING THEIR ACTIONS.

I have thought it necessary, before stating at length my own conclusions, to refer to some of the more important statements of authors concerning the subject of which I have to treat; because by so doing I may to some extent indicate what points are to be regarded as determined and proved, and what as still unsettled, and point out where I can agree with other writers, and where I am disposed to differ from them.

The opinions of authors on the general action of medicines are in most cases best ascertained by observing the manner in which they have arranged and classified them, grouping together those which they consider to be alike in their mode of operation.

Differences of opinion respecting individual medicines will be best considered afterwards, when we come to discuss those medicines. We are now to make inquiry as to the action of classes and groups. So that, in examining classifications as a key to the opinions of writers on this matter, we are only concerned with those which are founded in some way on the effects and operations of medicines.

Now there are three different points of view from which the action of a medicine may be regarded. We may ask,—1. What is the ultimate effect of its action on the system? 2. To what organ or tissue is its action directed? 3. In what way does it operate?

In other words, we may speak of the result of the action of a medicine, of the direction of the action of a medicine, or of the mode of operation of a medicine.

The first of these questions is the simplest, and may be answered from experience. We know that one medicine is a purgative, because it opens the bowels. We call another an alterative, because the manifestations of vital action are somewhat different after its use from what they were before. The last question is the most difficult to answer, because it involves the exact mode in which a medicine first behaves itself, so as to bring about its recognised operation.

Though the arrangements and theories of authors have generally taken into account all three of these questions, yet they have usually given greater prominence to one or other of them. And according to this their predominant idea, I will take the liberty of grouping them into three schools for the sake of convenience; considering, first, some theories and therapeutical arrangements which are based upon the ultimate effect of medicines; secondly, some that depend upon their local tendencies; and thirdly, some others that concern their mode of operation.

Among those who have directed attention to their ultimate effect, regarding that as generally sufficient for practical purposes, are included the great majority of those who have classified medicines. Such arrangements are practically useful, as by their means we are enabled easily to select a medicine which shall produce a required result. A classification founded upon local tendency is such as hardly to admit of practical application, for it is too vague. It is said that the action of mercury is directed to the blood; that of a tonic, to the muscular system. It is not said how they operate, or how these parts are affected. The terms employed are too wide and indefinite. Supposing the word Neurotic to signify a medicine acting on the nerves, we cannot say that any known medicine may not at some time or in some way act on the nervous system. The same term means a very different thing when found in a classification based on the mode of operation of medicines, for then it signifies a medicine acting on the nerves in a certain way which is defined, and it conveys to us an amount of information respecting that medicine and its applicability which we had not otherwise acquired. A classification of this third kind, though difficult of construction, would naturally be of great practical and scientific utility. The precise mode in which groups of medicines operate has first to be discovered and laid down, together with the results of that operation; and it has then to be proved that each remedy included in a class operates in the exact way predicated of that class. None which do not do so can be consistently included in it. Such an arrangement is precise; there may be a great deal of error, but there is very little vagueness about it. Each name and term should contain in itself and in its position an exact description of the general action of the substances included under it. Such an arrangement I have attempted to construct myself, as it is with the mode of operation of medicines that I am particularly concerned. The chief and obvious objection to such a classification consists in the insufficiency or insecurity of the data which we have to guide us. Thus the best and safest way is to select as the bases of primary subdivision those distinctions which admit of being the most readily and firmly established, and not to rest it on a number of uncertain or questionable hypotheses.

I. Opinions concerning the ultimate Effect of Medicines, and Classifications founded on this.

Most authors have grouped remedies together according to the broad results of their action. They do not make inquiry as to the mode of operation or behaviour of a medicine after passage into the system; nor do they ask whether this action is especially directed to any organ or tissue; but they judge by external evidence of its ultimate effect on the body, and on the powers of life.

There is commonly a tendency to describe all medicines under two heads, as either causing or diminishing vital activity. Dr. Murray indeed confounds these two effects, and adopts an idea on this subject which was originated by Mr. Brown. I shall now represent in an abridged form the classifications adopted severally by Dr. Young, Dr. Duncan, and Dr. Murray.

In the names of these three classes some reference is made to the modus operandi of medicines, but the distinctions thus attempted to be drawn are of the slenderest possible description. Among chemical agents are included some that are applied externally, and act then on the tissues in obedience to known chemical laws. But how can we affirm that some medicines passing into the stomach may not operate chemically? The term vital signifies little; and the word insensible, applied to the third class, is a confession of absolute ignorance. It does not attach to a medicine any distinctive character to say that we know nothing of its operation. Pursuing the subdivision further, we find that the distinctions are not well maintained. Tonics support strength as well as cause action; and it can hardly be said that the action of an Alterative, such as mercury, is partial and transitory. It seems unwise to have made a separate class of Specifics. They are especially associated with Alteratives. Mercury, Iodine, and others, would fall under both groups. Of Evacuants it may be observed, that they are also Exhaurient, and thus included in two opposed classes; that their action is not always partial and transitory, as, for example, Purgatives may permanently remedy constipation; and that it seems wrong to have separated Diaphoretics from them.

Thus neither the primary nor the secondary subdivisions of this arrangement can be reasonably maintained in theory, and we must fall back on the ultimate groups which are based upon common experience. From this failure we may infer that the idea that medicines differ prominently in causing or diminishing vital activity, upon which idea this and many other arrangements are founded, is in fact an erroneous one. There is no such universal distinction. A medicine which at one time raises or excites the vital forces, may at another time depress them; it may do one thing with a sick man, the other thing with a healthy man; it may have the one effect when taken for a short time in moderation, the other effect when taken for a long time or in excess. In fine, the result of the operation of a medicine does not necessarily depend upon this alternative. Although there are undoubtedly some medicines which tend to stimulate the nervous forces, and others which tend to depress them, yet as there are many remedies which may operate well without doing either the one or the other, and whose operation does not depend at all upon this, the distinction cannot be generally applied.

The next arrangement, that of Dr. Duncan, appears, as far as it extends, to be correct in theory. If some additions were made to it, it would be a tolerably perfect classification of this kind. Assuming as a basis the ultimate or practical effect of medicines, we may proceed to divide them into groups in a natural way. Food and liquids are of use in the nutrition of the tissues, and will form the first class. A second set of substances act so as to expel from the body certain humours and secretions. Another class exalt the tone of the nervous system, and through it stimulate the system at large. A fourth set depress the same. And a fifth group do none of these things; but their action results in certain obvious changes in the chemical nature of the secretions.

As far as it extends, this classification seems to be founded on correct data. The smaller divisions are natural. Thus Evacuants are grouped according to the part of the system at which the evacuation is made. General Stimulants are divided into those which are transitory in action, and those whose effect is permanent, as Tonics. Dr. Duncan is concerned only with the ultimate effect, and enters into no theory respecting the action of Tonics. I regard them as medicines acting primarily in the blood, and, applying my terms with a view to the modus operandi, I would restrict the term Stimulant to medicines acting on the nerves, whose effect is transitory.

The great fault of this arrangement is the omission of the very important class of Alteratives. We have medicines which increase secretion; medicines which exalt or diminish the vital energy; but where are the remedies which act in the blood? Where, for example, shall we place such medicines as Mercury, Arsenic, and Iodine, which neither act by eliminating, nor by stimulating, nor by depressing, but appear to counteract in the blood the agency of certain morbid poisons? In an arrangement founded on ultimate effect, they should be grouped in a class as Alteratives, as medicines which result in altering for the better the condition of the system. Both Dr. Duncan and Dr. Murray seem to have thought that no medicines could act in the fluids but such as have a well known chemical effect upon them. It cannot be that medicines should be able to affect the nerves, and to influence the glands, in divers ways, but that none should exert any action upon the blood, a most susceptible and changeable fluid, the medium of nutrition, the source of all the tissues, the "fons et origo" of disease. It is only very lately that authors have begun to recognise and include in their arrangements the class of blood-medicines, which seem to me to be considerably more important than any other.

Having shown thus what appear to me to be the correct bases upon which an arrangement of this kind should be constructed, I shall quote as another specimen the classification of Dr. John Murray, but mentioning only its most prominent details.

We find in this division some reference made to the local tendencies of medicines. Evacuants are classed as Stimulants which tend to act locally on the glands. In the arrangement of Dr. A. T. Thomson, founded upon this one, still further reference is made to the local tendencies of different medicines. Dr. Paris also has adopted this arrangement, but in a very much improved form. Both Dr. Thomson and Dr. Paris take exception to the inclusion of Sedatives (under the head of Narcotics) among general Stimulants. This is the great fault of Dr. Murray's classification. The idea, as he states, was taken from Brown. It is considered that both Stimulants and Narcotics act alike; that is, that they both produce a primary stimulation followed by a secondary depression; only that, in the case of Narcotics (under which head all Sedatives are included) the stimulation is very brief, and rapidly passes away, to be followed by a great depression. Now, even if this were true, the most prominent action would be the depressing effect, and it is on the most prominent action that denominations such as these are usually based. But it is well urged by Dr. Thomson that in the case of true sedatives there is no stimulant action whatever; and it is manifestly unreasonable to suppose that the depressing effect follows as a consequence on the primary stimulation, when the latter is so inconspicuous. At any rate such an arrangement as that of Dr. Murray can be of little practical utility in its original form. A man would be considered to be indulging in the wildest and most dangerous fancies who would run through the catalogue of Narcotics when he desired to produce a general stimulant effect. To this system it might further be objected, that Alteratives are again entirely omitted; and that the class of Mechanical agents would seem to belong to the division of Irritants, included among Local Stimulants. Dr. Murray classes Refrigerants among Chemical remedies, for which, when I come to speak of Acids, I hope to show that there are good reasons.

II. Opinions concerning the Local Tendency of Medicines, and Classifications founded upon this.

Here another step is made in the explanation of the action of medicines. They are said to have particular tendencies towards certain parts of the body, over which parts they exert a peculiar and special influence. It is thought that we shall make an advance in our knowledge of the subject, if we can discover what these tendencies are. An arrangement of medicines may be made accordingly. It is certainly more scientific than a merely empirical arrangement; and it will be so far of use that it will enable us, when we wish to make an impression on a certain organ or set of organs, to select those medicines which especially influence it or them. There is no doubt whatever of the existence of these local tendencies. There is no doubt that some medicines, such as Iodine, Bromine, Mercury, and Iron, tend especially to affect the blood and the blood-making organs, as the liver and spleen, rather than to act on the nervous or glandular systems. That some tend particularly towards the nerves, and prefer individually different parts of the nervous system, as Opium acts on the brain, Aconite on the superficial sensory nerves, Digitalis on the organic nerves of the heart, and Stramonium on those of the lungs. Again, it is evident that some medicines tend to act on the organs of secretion; and of these, particular sets select particular glands, as Diuretics the kidneys, Diaphoretics the glands of the skin, and Purgatives those of the bowels. There may be disagreements on minor points, but there can be no dispute as to the fact of the existence of these local partialities.[7]

But, though such statements are admitted to be correct in theory, it remains still to be considered whether they form a fitting basis for a classification of medicines. Now it will be observed that no theory of action enters into such an arrangement, but merely the tendency of the action of each medicine is considered; and as each medicine has naturally many distinct tendencies, it comes therefore under many different heads. But the chief practical use of a classification seems to be, that we may quickly learn from it the general action or effect of a medicine; so that, if it is stated to have many different tendencies, and is ranged under no one particular head, we can gain from this no very distinct practical information respecting it. In an arrangement of the kind that we have last examined, the most important result is the chief point considered. Thus it is rendered useful. And in one of the third kind, where the mode of operation is the great thing taken into account, as each remedy has only one primary operation, and according to this is classified, we gain from its designation some useful information respecting it. It may sometimes come under another head in its secondary operation, but only according to the primary should it be classed, the other term being supplementary. The designations founded on local tendency are further of an indefinite character, because they do not denote the kind of action exerted.

Of such a kind is the classification adopted by Dr. A. T. Thomson, founded on that of Dr. Murray. He divides what he calls Vital remedies into one division that acts on the nervous system, a second that affects the secerning system, and a third that influences the muscular and sanguiferous systems. This is certainly a step in the right direction. Nerve-medicines seem to have no relation to those that act on the glands, though connected with them as Stimulants by Dr. Murray. They are thus separated. Tonics are also separated from Stimulants, and included with those which act on the muscular and sanguiferous systems. This seems to me to be a correct view of their action. I do not consider that they act primarily on the nerves, but on the blood. Dr. Thomson places Astringents beside them. Though alike in some points, as with regard to their tendency to affect the condition of muscular fibre, yet there appears to be very little agreement in the mode of operation of Tonics and Astringents. There is not altogether much similarity between Quina and Sulphuric acid.

I will now transcribe the chief divisions adopted in the classification of Eberle, which seems to have been the prototype of that one since so ably elaborated by Dr. Pereira.

The subdivisions are founded on the kind of effect produced. As in Dr. Thomson's arrangement, Tonics and Astringents are said to act on the muscles; but no mention is made here of either of them acting on the blood. While Narcotics are placed among nerve-medicines, Stimulants are classed as acting on the circulating system. They no doubt act on the nerves, and then through them on the vessels; but so also do Narcotics, from which they are separated. If in class E are only included medicines acting on the organic nerves of the heart and arteries, why were they not placed in D, with Nerve-medicines? But if medicines acting on the contents of the vessels are meant, why were not Blood-medicines, or Alteratives, placed here? They are entirely omitted; which seems to be a fault in this system.

Dr. Pereira seems to have adopted a more correct view of both of these cases. He includes Stimulants with Neurotics, and places among "Hæmatics" those medicines which are commonly termed Alteratives. It seems to me that when a medicine acts on the blood, this action ought not to be thrown into the shade, but should rather be placed before all its other operations, as being of more importance than any of them. Dr. Pereira arranges in six classes those medicines which are given internally, having previously made three classes of external or topical agents, with which we are not now concerned. Some of the classes are again divided into large groups, these and the other subdivisions being either based on more particular local tendencies, or on the physiological action of the medicine on the part to which its operation tends.

These groups, though differently placed, correspond to six of Eberle's seven classes. The class acting on the muscular system is omitted. The subdivision here is more accurate and scientific. Hæmatics or blood-medicines, are divided into two classes. Spanæmics the first of these, are named from their tendency to impoverish the blood.Hæmatinics including the compounds of Iron, tend to enrich it. In the first division are included the medicines commonly termed Alteratives, as well as Acids, Alkalies, the compounds of Lead, Silver, Copper, etc. In the selection of the above name attention is paid to the abstract physiological effect of these medicines, rather than to their therapeutical applications. The impoverishing of the blood may be the ultimate action of such a medicine as Potash or Mercury, but not exactly the primary operation for which it is used in medicine. It is produced by the remedy when taken in excess, and not when given in small doses. Neurotics, or medicines which act on the nerves, are divided into those which affect the brain and spinal system, and those which are supposed to influence the ganglionic system, and through it the heart and great vessels. (When we shall afterwards discuss the action of nerve-medicines, it will be seen that it is very difficult, if not impossible, to enforce this distinction.) The different kinds of Narcotics form the first division, while the second includes Stimulants and vascular Sedatives. The class of Eccritics includes all medicines acting on the glands, commonly called Evacuants.

The details of this arrangement, to which I shall at present venture to object, are, first, the multiplicity of classes, and secondly, the inclusion of certain medicines in the division of Cerebro-spinals.

Three of the classes seem to be superfluous, and only tend to confuse. There is a class of Pneumatics, acting on the respiratory organs. But Expectorants are found elsewhere among Eccritics; and those medicines which influence the nerves of the lungs, among Neurotics. The same with Cœliacs; for Cathartics, found among Eccritics, are the most important medicines acting on the intestines. Genetics contain medicines which control the uterine and sexual systems, which may all be reckoned among Neurotics. And yet this multiplicity of names is consistently employed in carrying out the principle of this classification, which is, to arrange according to the different parts of the system all substances which have any tendency to act on those parts.

Dr. Pereira makes four orders of Cerebro-spinals; three include different kinds of Narcotics, very minutely subdivided; another is called Cinetics. 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 among Neurotics. Emetics are classed by him among Eccritics; 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 is distributed 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 or modus operandi of medicines in the cure of disease, as a necessary basis of such distinctions.

III. Opinions concerning the Mode of Operation of Medicines, and Classifications founded on this.

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. 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.

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.

[CHAPTER III.]

ON THE GENERAL MODES OF ACTION OF THERAPEUTIC AGENTS INTRODUCED INTO THE STOMACH.

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.

Prop. I.—That the great majority of medicines must obtain entry into the blood, or internal fluids of the body, before their action can be manifested.

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 by internal 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 surface is 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 not necessary, 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 fortiori would 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 not the 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 of possibility, 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 I mean 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 by Counter-irritation or Revulsion, 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. (Vide Prop. 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 called Shock. 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 of medicines, 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.

Prop. II.—That the great majority of medicines are capable of solution in the gastric or intestinal secretions, and pass without material change, by a process of absorption, through the coats of the stomach and intestines, to enter the capillaries of the Portal system of veins.

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 of Absorption and Endosmosis have 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; we have 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 Dutrochet Endosmose and Exosmose, according as the current tends inwards or outwards.

There are fluids on both sides of the membrane. The circumstances which determine their passage are mainly five. 1. The densities of the liquids: other things being equal, the lighter of the two tends to pass through to the heavier, more than the heavier to the lighter. 2. Their attraction for the intervening membrane.—That one passes through most which has the greatest affinity for the membrane. 3. The affinity of the fluids for each other.—A fluid passes through more rapidly when it is readily taken up and dissolved by that on the opposite side. By virtue of the last two laws, but contrary to the first, water passes through to alcohol more rapidly than alcohol to water. 4. The motion of the fluid on one side promotes the passage through of that on the other, because it is carried off as fast as it permeates the membrane. This also will cause endosmosis in defiance of the first law. This may be proved by a simple experiment. Let a large vein, cleanly dissected, be attached at one end to the stopcock of a vessel containing pure water. Let it then pass through a basin containing a strong solution of Ferrocyanide of Potassium, and let the other end hang over a jar filled with a solution of the Sesquichloride of Iron. If the cock be now turned, and water be allowed to pass through the vein into the vessel beyond, the solution of Iron will quickly acquire the tint of Prussian blue; for the heavy solution in the central vessel has passed through to the simple water of the vein, mainly by virtue of the motion of the latter. It will be seen directly that this is a matter of considerable importance. 5. The last law is, that any pressure on the fluid on one side of the membrane has a powerful influence in determining the passage of the current from that side. (Vide Liebig's Animal Chemistry, p. 72; Liebig on the Motion of the Juices; and the Lectures of Professor Matteucci of Pisa.)

The mucous membrane and the coat of the capillary vessel beyond it are probably subject to about the same physical conditions of absorption as those which are thus found by experiment to regulate the passage of fluids through dead animal membranes.

As to the first condition, it is probable that the aliment or medicine which is digested, however solid and dense, may be diluted down by the gastric juice until the solution is of less specific gravity than the serum of the blood. With the second law we are not so much concerned, as the medicine after solution has generally no repulsion for the animal membrane. So also with the third, as the serum of the blood mixes readily with all watery fluids. The fourth, viz. the condition of motion, is of great importance; for by it the motion of the contents of the capillary vessels will tend powerfully to determine the passage through of the liquid on the other side. Fifthly, the influence of pressure on endosmosis is one which is certainly exerted in the case of the stomach and intestines, which are muscular, and during the process of digestion contract on their contents with considerable force. This contraction, together with the circulation of the blood in the capillaries, would doubtless be sufficient to determine the passage of the digested matters inwards, even in opposition to the first law.[23]

Under the first proposition I have shown that the majority of medicines are absorbed into the system. It is now seen where and how they are absorbed. But it still remains to be seen what particular substances or classes of medicaments are thus taken into the blood, and whether while so passing they undergo any modifications.

The following, then, are the chief classes which I believe to undergo solution and absorption in the intestinal canal. They comprise the great majority of all substances used either as food or medicine:—

1. Mineral substances soluble in water.
2. Mineral substances soluble in acids.
3. Mineral substances soluble in alkalies.
4. Vegetable products soluble in water.
5. Animal and vegetable substances rendered soluble by the gastric juice.
6. Fatty and resinous substances soluble in alkali.

1. All soluble mineral substances—acids, alkalies, salts, and soluble compounds of the earths and metals—are absorbed in the stomach and intestines. The conditions and the process of absorption have been already stated. When solid they are first dissolved, when in a dense solution diluted down by the gastric fluid before they are absorbed. Thin watery liquids are quickly taken up. Motion on one side, and pressure on the other, hasten the process. I am not inclined to make any exception to this rule. This leads me to make some remarks on the Endosmotic theory of the action of saline purgatives.

M. Poisseuille found that the serum of the blood would pass through an animal membrane to a solution of Sulphate of Soda of greater specific gravity. He thus concluded that an ordinary saline purgative of greater specific gravity than serum (1.028) acted by causing the passage of this serum outwards into the intestine, producing a watery evacuation. The theory was taken up by Liebig and Matteucci, and by Laveran and Millon. Dr. Pereira and Dr. Golding Bird have drawn some practical inferences from it.

It is said that when a saline is absorbed it produces diuresis, and no purging; that when it purges it is not absorbed; that when given to act on the kidneys, the solution should be so diluted as to contain less than five per cent. of the solid; and when administered as a purgative, the specific gravity should be considerably above 1.028. Now I do not deny that a weak solution is more likely to pass off by the kidneys, and a dense one by the bowels; but I consider this due to the fact, that the kidneys are the proper emunctories of water, and of such matters as are soluble in it. But I believe that these solutions are equally absorbed, both heavy and weak, and that the purging or diuretic effect depends mainly on the quantity of the salt, as the kidneys will not eliminate beyond a certain amount of it. I must allege, to support this view of the question, firstly, some arguments à priori; and secondly, some experiments which I have made to satisfy myself. To consider first the former. Analogy is certainly against this theory. Other purgatives from the vegetable kingdom produce their effect when injected into the blood, and are yet often powerfully hydragogue. What effect on the process of endosmosis can be exerted by Castor or Croton oils, or by calcined Magnesia? On turning to what we know of the theory of digestive endosmosis, we find that the solid parts of the food are diluted down so as to be absorbed, and that the influence of pressure is to be taken into calculation. It was laid down by the great Boerhaave that a necessary requisite for the formation and absorption of chyle was the contractile force of the viscera. (Van Sweiten's Comment, vol. i. p. 290.) This, in fact, would press the fluid into the absorbent vessels, even if against the other endosmotic forces. Further, a fundamental principle was insisted on by Dutrochet—that even when the liquids on the two sides varied in density, they would both pass through to each other, though in different proportions. The ultimate result of this would be, that a heavy saline solution would be diluted down to the specific gravity of the serum, and would then pass through. This point I have illustrated in my first experiment. Thus it seems that my view is favoured by these physical laws. But even if it were not so, I should not be inclined to admit that all the endosmotic processes in the living body were regulated by merely physical tendencies. This cannot be the case with some of the secretions. The bile is of higher specific gravity than the serum of blood. Urine in health is lower, but in diabetes often much higher. The production of these secretions, differing in density from the serum of blood, would be inconsistent with the first law of endosmosis. Lastly, we find that in many known cases the theory which I am contesting does not hold good. Seidlitz water and sea-water are both known to be purgative. In both the specific gravity is below that of the serum of blood.

The first, according to Bergmann, has a density of 1.006. It contains in each pint 192.8 grains of solid matter. Out of this, 180 grains consist of Sulphate of Magnesia.

Sea-water has a specific gravity of 1.026, and its solid contents are about 3.5 per cent. But Dr. G. Bird says that less than five per cent. of saline matter constitutes a liquid diuretic.

These, then, are strong reasons against this idea considered merely as a theory. But it can readily be put to the proof. With this purpose I have made the following experiments. As far as they are concerned, they seem to show that salines are in all cases absorbed, and that whether they are subsequently excreted through the kidneys or by the bowels depends more on the quantity administered than on the degree of dilution of the dose.

Exp. 1.—A sufficient quantity of white sugar was dissolved in four ounces of water to raise its specific gravity to 1.028, that of the serum of the blood. Two drachms of sulphate of magnesia were dissolved in another ounce of water, so that the solution measured nine fluid drachms, and had a density of 1.060. This heavier solution was introduced into an open wide tube, closed completely below by a clean piece of bladder. It was introduced into a small vessel containing the solution of sugar, and arranged so that the height of the two liquids should correspond. After three days, the inner solution measured two drachms more, and the specific gravity had sunk to 1.050. The outer solution, after making up exactly the loss by evaporation, was found to have risen in density to 1.040. On adding a small quantity each of the solutions of phosphate of soda and carbonate of ammonia, a copious precipitate took place, indicating the presence of magnesia. Thus it appeared that the fluids passed both ways, some of the heavy solution of magnesia finding its way through to the lighter solution of sugar. The tendency of this process was evidently to an equalization of their densities, both by endosmose one way and by exosmose the other. Thus, apparently, would it be with a saline purgative, and with the serum of the blood.

Exp. 2.—Three drachms of Sulphate of Magnesia (a very mild purgative dose) were dissolved in ten ounces of water, and thus administered to a healthy young man. It produced, after some time, slight purging, and some diuresis. The urine, when tested, contained only a very little more than the usual quantity of magnesia. The quantity in the dose was less than five per cent. of the solution, and thus, according to the endosmotic theory, should have produced no purging.

Exp. 3.—Six drachms of the same salt were given in eighteen ounces of water to the same patient. After a few hours, it caused very copious and long-continued watery purging. The urine did not seem to be increased, and contained no excess of magnesia. It seemed, that in spite of the dilution, the quantity of the salt was so large, that it could not pass off by the kidneys, and so was eliminated from the blood by the bowels, in the same way as other purgative medicines. (Vide Chap. IV.)

Exp. 4.—This trial was the reverse of the last. Two scruples of Acetate of Potash were dissolved in three drachms of water, and thus administered. The solution then contained about twenty per cent. of the salt. According to the endosmotic theory, it should have caused only slight purging, on account of its density. It did not do so, but produced diuresis. The dose was so small, that after absorption it was easily eliminated by the kidneys.

These experiments are in favour of my views, and seem, as far as they go, to cast discredit on the theory of Poisseuille. It will be very easy to multiply them, so as to place the fact beyond a doubt.[24]

This point being so far settled, and there being no physical reason why any other soluble mineral substance should not be absorbed—it being, moreover, proved, by repeated experiments, that they all pass into the blood, we therefore proceed to the second class of bodies capable of absorption.

2. Mineral substances soluble in acids.—It is apparent that if any insoluble substance will admit of easy solution in the fluids of the stomach and intestines, it may be brought to the condition of a soluble one and thus absorbed. Now the gastric juice is acid. This secretion has been variously ascribed to free hydrochloric, acetic, phosphoric, and lactic acids; also to an acid phosphate or lactate of magnesia. There seems to be most reason to conclude that it is lactic acid, which would be easily formed out of the constituents of the food.[25]

But we have now only to regard the gastric juice as containing a free acid. This would reduce to solution the carbonates and oxides of all the metals; less perfectly when anhydrous, more easily when in the hydrated form. In this manner are absorbed the oxides of Iron and Silver, the carbonates of Lime and Magnesia, and other medicines of the same kind. They would be slightly modified, being absorbed in combination with the (lactic) acid of the stomach. In this they would differ somewhat from the substances already soluble, which would probably be absorbed unchanged, unless we except the alkalies and their carbonates, which might be similarly decomposed. Even these, if given in solution, would probably be absorbed faster than the gastric acid could be secreted to neutralize them.

Other insoluble substances, such as calomel and metallic sulphurets, would be more or less dissolved by the action of this acid. But as a great part would necessarily escape its influence, being propelled onwards by the muscular contraction of the stomach, it follows that insoluble substances of this kind are much less active as medicines than similar compounds introduced in a soluble state. It is also likely that a certain quantity would be sufficient to exhaust for a time the acid gastric secretion.

We now pass on to a third class of mineral products, which, though insoluble both in water and in acid, yet, being soluble in alkalies, appear to be in this way prepared by absorption.

3. Mineral bodies insoluble in water and in acid, but soluble in alkalies.—These remain unaffected by the action of the gastric juice, but on passing on as far as the centre of the duodenum, they meet with two alkaline fluids. These are the bile and the pancreatic juice. We know that some such insoluble bodies pass into the blood. It will be shown in the proof of the next Proposition, that they cannot do so without being first dissolved. Therefore, there must be in the intestinal canal something capable of thus dissolving them. For this purpose these two alkaline secretions are well adapted. As an example of such mineral bodies, of which there are not many, I may adduce sulphur. It unquestionably passes into the blood, and is found there in combination with alkalies, as a sulphuret or sulphate. It has been detected in the urine of those who were taking it, by Dr. Ronalds and others. It is possible that iodine, bromine, and some of the hydrated metallic oxides; may enter the blood in the same way.

4. Vegetable substances soluble in water.—These would be absorbed with more or less readiness according to their degree of solubility. They would probably be taken up in great part by the stomach. Some vegetable matters—as Lignine, or woody fibre, and Resins—are insoluble in water. Starch even is comparatively insoluble, and thus comes under another division, being probably one of those vegetable substances which are rendered soluble by the aid of the pepsin of the gastric juice.

These soluble vegetable matters are of several kinds. Cane-sugar and grape-sugar are readily soluble. So also are the various vegetable acids. There is another class of bodies which is highly important in a medical point of view. These are the natural salts of the vegetable alkaloids, of which are constituted so many of the active principles of plants. In pharmaceutical operations we are enabled, by the judicious employment of different menstrua, to extract from the crude and inert mass these vegetable active principles, and thus to obtain in a concentrated form the medicinal power for which each plant is esteemed. This process is also performed in the stomach. By digestion and concoction, with or without the aid of acid, it is enabled to dissolve out these soluble and potent matters from the ligneous and bulky tissues which surround them. For though the alkaloids themselves are in general almost insoluble in water, yet their natural salts which occur in the vegetable kingdom are mostly very soluble. The most important of these salts are as follow. In Cinchona bark, the Kinates of Quina and Cinchonia. In Opium, the Bimeconates of Morphia and Codeia. In Nux Vomica, the Igasaurate of Strychnia. In Aconite, the Aconitate of Aconitina. In Colchicum and Sabadilla, the Supergallates of Colchicia and Veratria. There are some neutral soluble substances, not partaking of the nature of Alkalies. Thus we find in Ipecacuanha and Ionidium, Emetine; in Tea and Coffee, Caffeine; in Willow-bark, Salicine; and the soluble active principles of Senna, Aloes, and Gentian, are probably of the same nature. Many other alkaloids are known. Atropia in Belladonna, Daturia in Stramonium, and Hyoscyamia in Hyoscyamus, occur in combination with Malic acid. Conia in Hemlock, and Nicotia in Tobacco, are peculiar volatile alkalies containing no Oxygen: thus in two respects they resemble Ammonia. They too are soluble in water.

Alcoholic and Ethereal fluids may be enumerated here as soluble products of the vegetable kingdom. Alcohol mixes with water to any extent; and one part of Ether is soluble in ten parts of water. Nitric Ether and Chloroform are also sufficiently soluble. So is Creosote, 1.25 parts of which dissolve in 100 of water. But this may be absorbed in another way, as will be seen presently. Volatile Oils and Turpentine come also under this head. They are all slightly soluble in water. The former, when given in small doses, are probably absorbed in this way. Turpentine, when given in large doses, may perhaps, by undergoing a change, come under the head of vegetable substances dissolved by alkalies. Camphor may be included here: one part is soluble in 1000 parts of water.

The soluble gummy matters of plants, when added to the substances enumerated above, constitute an aggregate which is called the watery extractive of a vegetable product: i.e. that part which is capable of being dissolved out of it by pure water.

But there are other active parts of vegetables, such as oily and resinous matters, and some neutral acrid principles, which, before they can be dissolved by water, require the aid of an alkali. These will be considered separately.

We now arrive at a fifth class of matters which are taken up by absorption.

5. Animal and vegetable products dissolved by the gastric juice.—The most important of these are the nitrogenous and nutritive constituents of the flesh of animals and of the parts of vegetables. Albumen, Glutine, Fibrine, and Caseine, are connected together as compounds of Proteine. Animal Fibrine, and the analogous Glutine of vegetables, are quite insoluble in water. Albumen and Caseine, though soluble, are immediately precipitated by acids. This is known to be at first effected by the gastric juice on their entry into the stomach. But the action of the gastric juice which contains an acid, and a peculiar nitrogenous material called Pepsin, —together with the temperature of the body, which is about 100°,—causes at length the gradual solution of these previously insoluble matters. This is found to take place out of the body when the above conditions are imitated with an artificial gastric fluid. The result of the process is a viscid fluid, which is then absorbed. The hard Gelatine of gristle and bone is not soluble in water at this temperature, but is readily soluble in the acid gastric juice. The Pepsine seems to be an important agent in this process, for an acid by itself is found to produce an imperfect solution. The nitrogenous matters thus digested and absorbed constitute that portion of the food which is of most use in the nutriment of the system; for the starchy compounds cannot be appropriated to the more solid tissues, although in some cases they may be converted into fat, as in herbivorous animals. (Liebig's Animal Chemistry, p. 113.)

Starch itself is one of this class. Tiedemann and Gmelin found that by the action of the gastric juice it was slowly converted into Dextrine, which afterwards changed into grape sugar. Both of these are very soluble. From the researches of Bouchardat and others, it appears that other fluids, as the Saliva, the secretion of Brunner's glands, and the Pancreatic juice, possess also this power of converting starch into a more soluble compound. So that if any of it escape the action of the stomach-secretion, it is probably reduced to solution and absorbed in the small intestine.

This change of starch is the first of a series of transformations, now ascertained, the ultimate result of which is its combustion and resolution into carbonic acid. Thus the nitrogenous compounds are called the nutritive, and the starchy materials the calorifacient elements of the food. Considered as medicines, these substances belong to the division of Aliments.

6. We have already considered some few mineral substances which are absorbed by the aid of the free alkali contained in the Biliary and Pancreatic secretions.[26] The sixth kind of absorbed matters consists of some vegetable and animal products which can only be rendered soluble by a similar agency. Fats and oils, resinous matters, and some principles resembling resins, come under this head. Fats and fixed oils consist of acids, as Stearic, Margaric, and Oleic, insoluble in water, in combination with a base, Glycerine, which, when isolated, is soluble. With a free alkali such a fat forms a soluble salt, called a soap, and the base Glycerine is set free.

In Man the Bile and Pancreatic juice are discharged together into the middle of the Duodenum. The fatty matters of the food are not absorbed before they meet with these secretions. But, after they have mixed with them, a milky fluid, called chyle, is formed, which is then taken up by the lacteal absorbents. It passes thence into the Thoracic duct, meeting there with an albuminous lymph, and is discharged at length into the general circulation at the junction of the left jugular and subclavian veins.

M. Bernard, in some papers laid lately before the French Academy, states, as the result of his experiments, that the function of the Pancreatic juice is to reduce the fat to the condition of a white emulsion. He states that no milky chyle is formed when the Pancreatic ducts are tied in dogs. He considers it absolutely necessary that saccharine and albuminous matters should be absorbed by the capillaries of the Portal veins, and then pass through the liver; and believes that the sole function of the lacteals is to take up fat thus emulsified. His experiments and inferences have received the high sanction of M. Magendie.

M. Frerichs has since affirmed that, whatever be the function of the Pancreatic juice, the Bile, by virtue of the alkali which it contains, is an indispensable agent in the absorption of fats. But M. Bernard has also found that the Pancreatic juice is always alkaline in health.

Whatever be the particular function of the Bile, it may reasonably be concluded that the alkali contained in one or both of these fluids is engaged in the saponification and solution of the emulsified fats. If it were not for this, this alkali would seem without an object; and further, it is contrary to all we know of the process of absorption to suppose that oil could pass through to a watery fluid without the intervention of an alkali to reduce it to the soluble state.

Thus it would seem likely that by means of the Pancreatic juice, with or without the aid of the Bile, fatty matters are first emulsified, in order to undergo an increase of surface, and then again saponified before they can be absorbed by the lacteal villi.

The principal fixed oils which are used in medicine are Castor, Olive, Almond, Croton, and Cod oils. It is certainly to be regarded as a very beautiful arrangement in the animal economy, that those substances which are not acted upon by an acid fluid should be subsequently subjected to the action of a free alkali, so that by the successive action of these solvents, together with the peculiar process of stomach digestion, the great majority of substances taken into the system are dissolved and rendered fit for absorption.

There seem to be other vegetable substances which are rendered soluble by means of alkali in the way already described. Resins form an important class of remedial agents, in which are comprised many Diuretics, Diaphoretics, and Purgatives. They consist chemically of peculiar acids, which, though themselves insoluble in water, combine with alkalies to form salts which are soluble. They are certainly in most cases absorbed. They have been found in the blood, and detected when passing out in the urine. From this last they may be precipitated by an acid, indicating that they are held in solution by an alkali. In large doses they may not be absorbed, but by irritating the surface of the intestinal canal, may act externally as Cathartics, and be expelled by the peristaltic action which they excite. But in small doses they enter the circulation in solution, and affect remote organs. The only way in which they can be dissolved is by means of the alkali of the two intestinal fluids. Among resinous medicines I may mention Catechu, Kino, Benzoin, Storax, Peru and Tolu, Copaiba, Guaiacum, the fetid resins, etc. Many purgative drugs, as Jalap, Scammony, and Gamboge, owe their efficacy to resin.

There are moreover certain neutral acrid principles, similar in their nature to resins, which are soluble only in alkalies, and thus come under this head. Such are Cantharidin, Piperin, Pyrethrin, Colocynthin, Elaterin, and Capsicin, obtained from Cantharides, Pepper, Pyrethrum, Colocynth, Elaterium, and Capsicum. But it should be observed that some of these are soluble in Acetic acid; and if, as some have supposed, this acid exist in the gastric juice, then they might be dissolved in the stomach.

We may add here some medicines which were enumerated also in a former division. Creosote, not very soluble in water, is easily dissolved in a free alkali. This substance also, like the last, is soluble in Acetic acid.

Some volatile oils, especially Turpentine, display a marked tendency to oxidize into resins; and being themselves very sparingly soluble in water, may perhaps be dissolved after having undergone this change. Thus Turpentine changes into common Resin, which consists of two isomeric acids, Pinic and Sylvic.

Turpentine = C₂₀H₁₆
Pinic Acid = C₂₀H₁₅O₂

and,

C₂₀H₁₆ + 3O = C₂₀H₁₅O₂ + HO.

or, Oil of Turpentine, with the addition of three atoms of Oxygen, produces Pinic acid, i.e. Resin, and an atom of water.

Now Turpentine, when given in large quantities, irritates the surface of the intestinal canal in man, and is not absorbed. But in the horse very large doses are found to pass through the system into the urine. It is not likely that a large quantity should enter in solution in water. It seems more probable that it may first in some way become oxidized, and then dissolved as a resin. The action of turpentine resembles that of some other substances which contain resin, as Copaiba and Balsam of Peru.

The resins thus dissolved would pass, like other solutions, through the mucous membrane of the intestines into the Portal capillaries.

But of the fats and fixed oils it cannot be said to be proved that they are absorbed in a state of solution, although such a conclusion is almost forced upon us by a consideration of the laws of endosmosis. They do not pass into the veins, but are taken up by the lacteal absorbents. They are capable of solution, and are thus not in that sense an exception to the rule of Prop. II. But in another sense they are an exception to it; for they do not pass directly into the veins, but through the lacteal system. It seems that the sole purpose of these lacteal vessels is to absorb fats. Thus it appears that all soluble substances, whether in the food or given as medicine, and in whatever manner rendered soluble, whether by acid, by alkali, or by stomach digestion, are absorbed in the stomach and intestines. All of them, with the exception of fatty matters, pass directly into the blood, traversing the mesenteric and Portal veins, to reach the liver. From this organ they pass on into the heart through the Vena cava inferior. I have shown also that they are mostly absorbed without material change. Supposing the stomach acid to be lactic, it would be too weak to displace mineral acids. It would, however, decompose a few insoluble matters, and combine with alkalies and their carbonates, forming salts which in the blood would again change into carbonates. (Vide Prop. VI.)

Prop. III.—That those medicines which are completely insoluble in water, and in the gastric and intestinal juices, cannot gain entrance into the circulation.

It may at first sight be objected to this proposition, that fatty matters may probably enter the lacteals in an undissolved state. But this is not proved; and besides, whether dissolved or not, we know that they are soluble in one at least of the intestinal juices—viz. the Bile. So that they do not come under the above definition.

We have just seen that many medicines which are given in the insoluble form are capable of being dissolved in the fluids of the intestinal canal. This so much reduces the list of perfectly insoluble medicines, that it is difficult to find any that come under such a definition. But Charcoal, the simple metals, woody fibre, and Nitrate of Bismuth, will serve as examples.

Sulphate of Lead is often quoted as perfectly insoluble; but this is not the case. It is soluble in a solution of acetate of ammonia. This salt is contained in the perspiration. Thus the sulphate, when substituted for the carbonate in some lead works at Paris, proved fatal to the foreman, who died of colic. M. Flandin found that it poisoned a dog when rubbed into the skin as ointment. Even some metals may possibly be brought within the influence of weak acids when in a fine state of subdivision, as Mercury in blue-pill. Gold in a very fine powder has been used successfully in syphilis.

Thus the list of insoluble substances is still further reduced. But there is no doubt that many substances which are slightly soluble in the intestinal fluids may in great part escape this solution, and pass out with the fæces just as they went in.

To assert that the particles of an insoluble substance cannot pass through the homogeneous wall of the capillary or absorbent vessels, is merely to state what follows from an absolute physical law, and is generally admitted by physiologists. But even this fundamental datum has been lately attacked.

Professor Œsterlen of Dorpat has been induced to affirm the possibility of the absorption of insoluble substances, from some experiments which he has made. Finely-powdered charcoal was administered to rabbits for some days. They were then killed, and globules of charcoal, measuring from 1/6000 to 1/3000 of an inch, were found in the blood of the Portal circulation. (Zeitschrift für Rationelle Medizin, 1847.) To obtain these results the microscope was used, a far less certain test in such matters than chemical analysis. Œsterlen reasonably concludes that, if charcoal can so pass, so also can any other insoluble substance. The necessity of solution could then at once be done away with, and the blood continually liable to admixture with all kinds of heterogeneous and crude materials. Œsterlen asserts further that he has found minute globules of mercury under the skin after rubbing in mercurial ointment. (Journal für Praktische Chem., No. IX. 1850.) Now, if these things were true, there could be no need to suppose the solution of insoluble active medicines, for they would be enabled without difficulty to pass through in an undissolved state.

To test for myself the accuracy of such statements, I have made some experiments, the object of which is to discover if some of the most insoluble of our known remedies, which are yet known to obtain entry somehow into the blood, could do so while yet in the insoluble state. They are as follow:—

Exp. 1.—Ten grains of calomel were given to a large dog. It was killed after three hours, allowing this time for digestion. A considerable quantity of blood was collected from the Portal vein, and submitted to analysis to determine whether it contained any compound of Mercury in an insoluble form. The blood was dried and pulverized. The result was boiled for some time in water, and the insoluble part collected. It was dissolved in a small quantity of aqua regia, and the clear acid solution placed in a test tube. A slip of zinc foil was folded round a narrow plate made of gold foil, and introduced into the solution. A galvanic current being thus set up, the minutest quantity of mercury, if present, would have been deposited on the gold, so as to tarnish it. But this did not take place, and when at last the zinc was completely dissolved, the gold remained as bright as before. Thus there was no Calomel, or compound of mercury, present in the insoluble form.

Exp. 2.—Ten grains of strong mercurial ointment (containing half its weight of metallic mercury, with some oxide) were given to another dog. He was killed after the same time, and the Portal blood analyzed carefully in the same way, but here also no mercurial compound was present in the insoluble form.

Exp. 3.—To a third dog five grains of Oxide of Silver were administered. After three hours he was killed. The Portal blood was dried in a water-bath, and reduced to powder. This was boiled for some time in water, which was separated by filtration. Aqua regia was then boiled on the insoluble part. This would convert any silver into chloride. The acid was evaporated off as much as possible, and the solid remainder heated in a small porcelain crucible to dull redness. The result was powdered, and digested in liquor ammoniæ. It was filtered, and excess of nitric acid was added. There was not any precipitate. Had chloride of silver been present, it would have been dissolved by the ammonia, and precipitated by the acid. Thus no insoluble silver compound was contained in the blood analyzed.

Exp. 4.—Ten grains of sulphur were administered in the same way to a fourth dog. On killing it and opening the body, the thoracic duct was found to be full. A considerable quantity of chyle was collected from it. Now, as it is asserted by some, that fat passes undissolved into the chyle, and as I believe that sulphur is digested in the neighbourhood of the bile duct, this chyle was chosen for analysis in preference to blood, as more likely to contain any insoluble sulphur. Besides, the blood would be less satisfactory, on account of the large quantity of albumen and fibrine contained in it, both of them also containing sulphur. The insoluble part of the chyle was obtained in the same manner as with the blood. It was then boiled in a small quantity of a weak solution of caustic potash. By this any free sulphur would be converted into a soluble sulphate of Potassium. The solution was filtered, and a few drops of a solution of the Nitro-prusside of Potassium added. (This is a salt lately discovered by Dr. Playfair. It is a delicate test for soluble sulphurets, with which it strikes a deep purple colour.) No change was produced. Therefore no insoluble sulphur was present in the chyle.

The results of these experiments are thus in direct opposition to those of M. Œsterlen, and support a view of the question which seems even à priori more philosophical and reasonable than that which he has adopted. I believe that no insoluble medicine can in any way gain entry into the blood without first undergoing solution in some way or another.

Prop. IV.—That some few remedial agents act locally on the mucous surface, either before absorption, or without being absorbed at all. That they are chiefly as follow:—

A. Irritant Emetics.
B. Stomach Anæsthetics.
C. Irritant Cathartics.

It has already been shown, during the consideration of the first proposition, that medicines which act on distant parts of the body must be, and are, absorbed before they can so act. This necessity for absorption has been shown to extend even to medicines which act most rapidly on the nervous system. If any medicines could produce a distant effect by a mere contact with the coats of the stomach, such a power would be ascribed to those stimulants and sedatives which, from the suddenness of their action, are called diffusible. Such are Hydrocyanic Acid and Ammonia. Their rapidity of action is to be ascribed to their volatility, whereby they spread over a large surface, and are almost suddenly absorbed and transmitted through the blood. But Hydrocyanic Acid may be absorbed from any surface. It is poisonous when inhaled into the lungs. It rapidly causes death when dropped into the eye of an animal. So also the results of the inhalation of ammoniacal gas are the same as of the ingestion of its solution. I believe that the latter, on account of its diffusibility and rapid absorption, escapes neutralization by the stomach acid, and passes into the blood as free Ammonia.

In the consideration of the first Proposition, I endeavoured to point out that though the proper action of a medicine could in no case be conducted, without absorption, from the mucous surface to a distant part of the system, yet that a remote action of another kind might occur as the result of a change in the nervous system produced by a powerful local impression. I stated that the term Counter-irritation was employed to express this action, the nature of it being but ill understood. A powerful impression on any surface of the body, external or internal, seems to be capable of arresting and diverting, as it were, the attention of the system, and thus, for a time, of checking a morbid process.

Frictions and Sinapisms act on the skin externally on this principle. So do Blisters and Issues; but they are not simply counter-irritants, for they also drain away the serum of the blood. It is not now within my province to consider such an action on the skin, any further than for the purpose of stating that similar local impressions on the mucous surface of the stomach and intestines are capable of operating on the same principle.

We have then to consider what are the local actions that medicines are capable of producing on these surfaces.

And first, it must be laid down as a rule, that all medicines, when given in excess, act as irritants on the stomach and intestines. This is more especially the case with mineral salts, with the bitter and astringent principles of vegetables, and with acrid and resinous matters. By irritating the stomach locally, they cause vomiting; by causing peristaltic action of the bowels, purging. Some of them are actually employed to produce these effects, and will be presently specified.

The corrosive and narcotico-acrid poisons may produce by this local action a degree of irritation sufficient to cause death. In the case of the first, some erosion of the mucous surface may occur. By both kinds violent vomiting and purging is apt to be produced, and succeeded by symptoms of collapse. These last, however, are not therapeutic agents, when in such doses.

Antidotes, employed to counteract these poisons, are remedies which are given to act locally in extraordinary cases. There are three chief kinds of them; Demulcents, to sheath the irritated surface, and protect it from further injury; Emetics and Purgatives, to get rid of the poison; and chemical antidotes, to neutralize it or render it insoluble while in the stomach. With this last object, acids are given in alkaline, and alkalies in acid poisoning. The soluble salts of Lead may be precipitated and rendered insoluble by sulphuric acid or sulphates. Those of Mercury, Copper, and Zinc, by albumen. Tannic acid precipitates the vegetable alkaloids. There are some other special antidotes of the same kind.

Let us now consider the three kinds of remedial agents in ordinary use, which are employed for the purpose of producing a local effect on the mucous surfaces, before absorption, or without absorption.

a. Irritant emetics.—Two kinds of medicines are employed to produce Vomiting,—specific emetics, and irritant emetics. The former act from the blood; the latter, by local irritation. In the same way that irritation of the external surface of the body will sometimes cause at the same time the direct contraction of a neighbouring muscle, and the reflex contraction of others at a distance, so does local irritation operate on the surface of the stomach. On the one hand the muscle of the stomach itself is caused to contract, so that, the pylorus being at the same time forcibly closed, it tends to expel its contents in the wrong direction. On the other hand, a large set of distant muscles is thrown into sudden action. First, a quick deep breath is taken by means of the inspiratory muscles. Then the aperture of the glottis is spasmodically closed, so that, the lungs being full, the diaphragm cannot be pushed upwards. Then immediately the abdominal muscles contract, and being unable to act on the diaphragm, they press on the stomach, emptying it forcibly of its contents.

All this is by reflex action, and follows sympathetically the contractions of the stomach, co-operating with it, and resulting, like it, from irritation of the sensitive mucous surface.[27] Such is the action of an irritant emetic.

Now, Tartar Emetic and Ipecacuanha do not act in this way. When injected into the blood elsewhere, in sufficient quantity, they are found to produce vomiting. They have also special actions on the heart and lungs, which are not possessed by merely irritant emetics. They seem to me to act specifically on the Vagus Nerve, which is supplied to these organs as well as to the stomach, and to cause vomiting by deranging its functions. By this action on the Vagus while in the blood, they excite, in a special way, the same reflex contractions which are produced, in the case of an irritant emetic, by irritation of the extremity of that nerve in the mucous membrane. They are thus Neurotics, or nerve-medicines. They are not gland-medicines; or, at least, there is no proof that they are excreted by the stomach, and thus they do not come under my definition of Eliminatives. All substances which touch the surface of the stomach cause it to pour out its secretion.

Specific emetics cause nausea, even without vomiting, depressing the action of the heart by their influence over the Vagus nerve. Irritant emetics scarcely cause nausea, producing only a feeling of discomfort, arising from the inverted action of the stomach.

The Sulphates of Zinc and of Copper; common Salt, and among vegetables, Mustard and Horse-radish, are used as irritant emetics. They cause, by contact and irritation, a large quantity of the gastric juice to be poured out. This, together with the emetic, and any contents of the stomach, is rejected. The process is not followed by much inconvenience.

Such emetics are chiefly used when we wish to unload the stomach of any irritating or poisonous matters; but not when our object is to cause nausea, depression of the heart's action, or relaxation of the muscles. The violent action which they produce may possibly act on remote parts on the principle of counter-irritation. Thus emetics of various kinds are often administered in the early stages of inflammatory disorders, and have been known sometimes to cut them short. But such an effect is much more likely to be produced by a specific emetic, which adds to this counter-irritant action the production of nausea, by which the force of the heart is powerfully depressed, and the pulse reduced. Tartar Emetic, the most powerful of these specific agents, must doubtless be absorbed to a certain extent before it can produce its effect. Thus the important difference between the modes of operation of irritant and specific emetics is, that the former do not produce vomiting when injected into the blood, but act locally; whereas the latter act from the blood on the nerves. (Vide Prop. VIII., Specific Sedatives.)

b. Stomach-Anæsthetics.—There is a class of medicines used in Gastrodynia which seem to act locally on the sentient nerves of the stomach, in the same way that Aconite acts on the superficial nerves of the skin. Although the majority of them are subsequently absorbed, yet, in order to exert this particular action, it is not necessary that they should pass beyond the substance of the stomach itself. They do not seem to have any special or peculiar tendencies towards the stomach nerves. But if introduced into the blood elsewhere, they would not pass the nerves of the stomach in so concentrated a form as when coming directly from the mouth, and thus would not be so useful as stomach-anæsthetics. Thus this action depends upon local contact, and is so far a local action.

Hydrocyanic acid, Creosote, and Nitrate (also called Tris-Nitrate) of Bismuth, are the most useful of these medicines. The first two are subsequently absorbed, and pass into the blood. The third is a very insoluble salt. It acts also as an astringent on the mucous surface of the intestine, and is probably the only astringent which is not absorbed. Being insoluble, its action is quite confined to the mucous surface. It may be given safely in very large doses, (as ʒss, or even ʒj.) and it is likely that its anæsthetic action may be in some part mechanical in nature, and depend upon its affording a mechanical sheath to the irritable and painful surface of the stomach. Hydrocyanic acid and Creosote,—general sedatives,—act locally as anodynes to the nerves of the stomach.

c. Irritant Cathartics.—As there are two kinds of emetics, differing in their mode of operation, so also do there seem to be two kinds of Cathartics. But the distinction between them is not exactly the same. As with the Emetics, one kind seem to act by topical irritation, exciting an outpouring of the intestinal secretions, and causing an expulsion of the contents by exciting peristaltic contraction. But Specific Emetics, which act from the blood, seem to produce their effect by influencing the nerve of the stomach; so that they are Neurotic medicines. Specific Cathartics act differently. They are truly Eliminatives. They exert no influence over nerves, but they operate by passing out of the blood through the intestinal glands. Like Specific Emetics, they must be first absorbed. I will not now enter into the theory of Elimination, which I shall have to consider afterwards, but I wish merely to distinguish between local action on a surface, and specific action on a gland, exerted from the blood. Many substances used as purgatives are capable of absorption, and are absorbed. But it seems that they are not fit to remain in the blood; and after passing round in the circulation, they are expelled by the depurative force at a point near to that at which they previously entered by the laws of absorption, namely, the mucous surface of the bowels. They are most commonly expelled by the glands of this surface somewhere in the lower or fæcal portion of the intestinal canal, which is more engaged in secretion, but less active in absorption, than the upper part. The increased secretion which they excite causes peristaltic action, which expels both it and them, so that they cannot again be absorbed.

Such a specific Cathartic would be capable of acting thus if introduced into the system at any point. Castor Oil and Croton Oil, whether received into the stomach, or injected into the veins, or introduced into the system at any part, equally produce purging. So also do Rhubarb, Aloes, and Senna. The principles of these medicines have been detected in the blood by Tiedemann, Gmelin, and others. Colocynth and Elaterium have also been proved to act specifically.[28]

It is to be inferred from analogy that other resinous Cathartics, as Jalap, Scammony, and Gamboge, must also act from the blood. It has also been shown that both from actual experiment, and from a consideration of the laws of the process of absorption, we must conclude that saline Cathartics are absorbed into the blood before they cause purging.

But we have now to do with Cathartics that act by topical irritation. Which are they? I believe that the same resinous Cathartics which have the power of acting specifically, may have, especially when in large doses, a double action. It has been shown that resins are difficult of absorption; and whether they be absorbed or not, we know that they must irritate the intestinal surface, from the violent griping which often attends their operation. Thus Scammony does not act so well, and does not gripe, when the bowels are lined with mucus. Gamboge and Euphorbium are irritant in an extreme degree, and are therefore too dangerous for general use. The powder of Euphorbium resin has been used as an Errhine, for, by irritating the mucous membrane of the nose, it increases its secretion. This illustrates the operation of irritant Cathartics. A great part of the fæces is secreted by the mucous membrane of the bowel. This secretion a Cathartic may increase by mere contact and irritation; or, being also a specific agent, by absorption and elimination likewise.[29]

Some Cathartics employed as Vermifuges, as the hairs of Mucuna pruriens, metallic Mercury, and Tin powder, cannot be absorbed at all, and must act solely and altogether by irritation.

These Vermifuges, or Anthelmintics, are employed for a strictly local purpose—that of killing and expelling intestinal worms. Any powerful Cathartic may be used to expel them. But such an agent should generally be conjoined with a medicine that tends directly to kill the parasite; for after that it will be more easily dislodged. For this purpose the root of Male Fern, Kousso, and the bark of the root of Pomegranate, have been used with advantage in the case of tape-worm. Ascarides are situated low down in the intestine, and may be dislodged by the use of an enema, as of Salt.

Turpentine is often very efficacious in cases of this kind, being at once a poison to the worms and a powerful irritant cathartic.

I have already alluded to Nitrate of Bismuth, as seeming to be an astringent to the mucous surface of the intestine, although apparently incapable of absorption. It has been used with advantage in diarrhœa, and is highly recommended by Dr. Theophilus Thompson in the diarrhœa of Phthisis.

But all other astringents are absorbed; and when they act on the mucous glands of the intestines, it is probably from the blood.

It has been supposed by M. Poisseuille and others that the action of Opium in confining the bowels is to be attributed to a power of checking the process of endosmosis, said to be possessed by a solution of Morphia. I shall afterwards state my reasons for discrediting this explanation. (Vide Chap. IV., Art. Opium.)

Thus we have concluded the list of substances which seem to act locally on the mucous surface, without passing into the blood.

Having previously endeavoured to explain the various modes in which medicines are absorbed and pass into the blood, and having now defined the action of some few before absorption, the greater part of our investigation remains still to be accomplished. The actions of medicines in the blood, and their various and complicated operations in the cure of diseases, have to be traced out, and, if possible, accounted for.

The remaining six Propositions concern the behaviour of medicines after their passage into the blood. The first two of them are comparatively unimportant. The Fifth is merely an extension of the First Proposition,—in which the same rule is applied to the blood which was there proved of a surface,—and indeed follows in part from the latter. The Sixth Proposition defines three kinds of changes which certain medicines are liable to undergo during their stay in the system.

Prop. V.—That the medicine, when in the blood, must permeate the mass of the circulation, so far as may be required to reach the parts on which it tends to act.