Chapter 2 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.

Dr. Young

1. Chemical Agents.

Caustics, etc.

2. Vital Agents.

A. Supporting strength.

Nutrients.

B. Causing action.

(Partial and transitory.)

Stimulants, Irritants, Astrigents, Alteratives, Evacuants.

(Permanent.)

Tonics.

C. Diminishing action or sensation.

(Primarily.)

Narcotics, Nauseants, Sedatives, Diaphoretics.

(Secondarily.)

Exhaurients.

3. Insensible Agents.

Specifics.

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.

Dr. Duncan

Alimenta.

Diluentia, Demulcentia

Evacuantia.

Diaphoretica, Errhina, Expectorantia, Cathartica, etc.

Stimulantia.

Topica (irritants, etc.)

Generalia permanentia.

Generalia transitoria.

Deprimentia.

Refrigerantia, Narcotica.

Chemica.

Acida, Alkalina.

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.

Dr. Murray.

General Stimulants.

Diffusible

{Narcotics.

{Antispasmodics.

Permanent

{Tonics.

{Astrinents.

Local Stimulants

Evacuants, Irritants

Chemical Agents.

Mechanical Agents.

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.

Dr. Eberle's Classes.

A. Medicines acting on the intestinal canal, or its contents.

B. Medicines acting on the muscular system.

C. On the uterine system.

D. On the nervous system.

E. On the circulating system.

F. On the organs of secretion.

G. On the respiratory organs.

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 "H?matics" 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.

Dr. Pereira's Classes.

Class IV. H?matica.

1. Span?mica.

2. H?matinica.

Class V. Pneumatica.

Class VI. Neurotica.

1. Cerebro-spinalia.

2. Ganglionica.

Class VII. C?liaca.

Class VIII. Eccritica.

Class IX. Genetica.

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. H?matics or blood-medicines, are divided into two classes. Span?mics the first of these, are named from their tendency to impoverish the blood.H?matinics 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 C?liacs; 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 lamell?.[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 Pharmacop?ia 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 Vit? 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 Pharmacop?ia 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 H?matolytica Physoda; and alkalies prevent the coagulation of the fibrine of the plasma, for which reason he calls them H?matolytica Plasmatoda.

Some modern writers have tried to extend a chemical theory to the operation of medicines in general. This is an error to which those who have devoted themselves particularly to the study of chemical phenomena are especially prone.

Müller thinks that the agency of many remedies may be explained by their chemical affinities. He supposes that they may effect a change in the nutritive fluids, or that they may so disturb the state of combination in which the elements of an organ may be, that it becomes insensible to the action of morbid stimuli. Some chemists have accounted for the action of Alcohol by its chemical affinity for the brain substance. Liebig considers that the similarity of their composition to that of the brain may serve to explain the operation of such medicines as Quina and Morphia. Such ideas as these are at the best purely hypothetical, and even as theories they seem to me to be untenable,-for what reasons I shall have to show when I consider these remedies. Liebig has hazarded several other explanations of a similar kind, of which the following is an example:-"The frightful effects of Sulphuretted Hydrogen and Hydrocyanic Acid are explained by the well-known action of these compounds on those of Iron, when Alkalies are present, and free Alkali is never absent in the blood." (Organic Chemistry, p. 274.) Now in the first place it is not proved that the complete abstraction of iron from the blood would occasion sudden death, though doubtless it is a necessary constituent of that fluid. Further, Prussic Acid acts on the superficial nerves as an Anodyne when applied externally, which it can hardly do by displacing iron. Besides, by parity of reasoning, Ammonia, or Benzoic or Cinnamic Acid, should precipitate iron, if present in the blood in the soluble state, and Sulphuric or Nitric Acid should dissolve it, if in the state of peroxide; and yet none of these agents are frightful poisons. It is not to be imagined that chemical solutions and decompositions of every kind are allowed to take effect in the human system in the same way as in the laboratory of the chemist, for there are in the former many disturbing and controlling causes which suffice to hold them in check.

We may altogether conclude, that though the actions of many remedies may be partly elucidated by chemical considerations, it is impossible to account for the influence of all alike in this way. For at least the actions of nerve-medicines and of gland-medicines cannot be reasonably explained on any such hypothesis.

3. The most plausible explanations of the mode of operation of medicines have been founded on vital or general principles. By vital I mean that these theories concern actions which could only take place in the living body. They may be termed general principles, because the grounds on which they are based are neither mechanical nor chemical, but something different from both. The term dynamical has sometimes been applied to an ill-understood vital action of this sort.

Many different ideas have been broached to account thus for the action of medicines. Some, who have constructed very ingenious and plausible systems, have explained in different ways the operations of different groups of medicines. But when others have adopted a single inflexible hypothesis to account for the action of all alike, this is found, as might be supposed, to be of a very untenable character. I will now consider very briefly several such ideas; first, for the sake of clearness, dividing them into seven sections. I shall explain my meaning as I proceed. Different writers have supposed that the general operation of remedies in the cure of disease is conducted in these various ways.

a. By degrees of stimulation.

b. By counter-stimulation.

c. By opposition.

d. By similar agencies.

e. By elimination.

f. By alterative actions.

g. By various counteractions.

a. This idea has received the title of the "Brunonian Theory," from the name of its founder. It was promulgated by the famous Dr. John Brown at the close of the last century. He considered all diseases to arise from excessive or diminished "excitement." He was of opinion that all medicinal agents were stimulants, only that some acted so powerfully as to produce "indirect debility." These latter were to be used in sthenic, the others in asthenic disorders. But it is to be urged against this idea, that many sedatives produce no appreciable degree of "primary stimulation;" that alterative medicines are neither stimulant nor depressent; and that the actions of different therapeutic agents,-as, for example, of Opium, Mercury, and Rhubarb,-differ very much in quality, and not simply in degree, as Dr. Brown supposed. The principle, then, cannot be maintained.

b. Rasori and other Italians adopted a similar idea about the commencement of this century, only that they supposed two contrary agencies, instead of variations in the degree of the same action, like the Brunonians. Giacomini classified medicines on this plan. The two classes of medicines are termed "Hypersthenics," and "Hyposthenics,"-i. e. Stimulants, and Contra-stimulants, or Sedatives. These were to be used respectively in asthenic and in sthenic disorders. But this idea did not originate with these physicians. It prevails among the modern Hindoos, and seems to have been inculcated by certain medical writers of that nation in very remote times. (On the Hindoo System of Medicine, by Dr. Wise, 1845, p. 213.)

c. The last-mentioned idea supposes only one kind of opposition, and therefore only two descriptions of diseased action. But a much more plausible notion than that is, that each particular disease or symptom is to be cured by administering a remedy which is capable of producing a contrary state. By this contrary condition the disorder is to be neutralized. This was the maxim of Hippocrates-τα εναντια των εναντιων εστιν ιηματα-"contraries are the remedies of contraries." (De Flatibus, par. iii.) On this principle we give purgatives in constipation, opium in diarrh?a, 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 diarrh?a, on the "Hom?opathic" principle. But it should be observed that the sweating in one case, and diarrh?a 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 hom?opathists 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 hom?opathists 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 natur?," than to make rash or violent attempts at a cure. He maintained that what we call a disease was in fact "no more than a vigorous effort of nature to throw off the morbific matter, and thus recover the patient."[14] He proposed, therefore, that our efforts should be directed to assist nature to procure the evacuation of a poison, promoting its elimination by acting on the various secretions-as by purgatives, diaphoretics and such medicines. For he had noticed that in fevers and febrile disorders the crisis or turning-point was generally accompanied or preceded by an increase in one or more of these secretions, and he regarded this as an indication of the treatment to be pursued in all such cases. "That," said he, "appears to be the best method of curing acute diseases, which, after nature has pitched upon a certain kind of evacuation, assists her in promoting it, and so necessarily contributes to cure the distemper."[15] He further proposed, that in the treatment of chronic diseases, when nature herself was slow in procuring this evacuation, we should seek for specific medicines, by which we might assist her in doing so, and thus effectually expel the morbific matter. This theory was reasonable and natural compared to those that followed it; but it was nearly extinguished and forgotten amid the war of opinions which was subsequently kindled by the aphorisms of Boerhaave. About this time we find Dr. Pitcairn mixing up this idea with his mechanical notions, in a treatise "On the Cure of Fevers by Evacuation." Huxham also, in 1729, maintained similar principles.

At the present day a more enlarged view is adopted. It is admitted that we may often assist these attempts of nature at a cure, and do good by the use, when thus needed, of evacuant medicines; but at the same time we must allow that there are many other advantageous modes of treatment,-that we may sometimes cut short a disease in the blood, or relieve a disorder by controlling vascular or nervous excitement, without resorting to elimination at all.

f. M. Broussais was one of the first who rightly maintained that many medicines were of use by means of an alterative or revulsive action, by producing a distinct effect which diverted the attention of the system from the disease. His followers have classed remedies under three heads,-as Stimulants, Debilitants, and Revulsives. He maintained also some other peculiar ideas.

Blood-medicines are commonly termed Alteratives, from the notion that they divert or alter the original disease by setting up in the system a peculiar process of their own. The term Revulsive is especially applied to medicines which produce a powerful local effect, and are supposed so to occupy the attention of the system as to tend to cure the disease which formerly engaged it. Counter-irritants externally, and emetics among internal medicines, are generally admitted as revulsives.

The idea of revulsion is a prominent feature in the arrangement of medicines adopted by Dr. Schultz, of Berlin, who adds to the above, Expectorants, Purgatives, Diuretics, and Sudorifics. He divides medicines into Biolytics, tending to dissolve life and structure; Anabiotics, which tend to stimulate the same; and Agonistics, tending to produce a "defensive" process, and acting by revulsion. Each class is again divided into those which affect the organs and nutrition in general; those which act on the blood; and those which particularly influence the nerves. I will give examples of each.

Schultz's Classification.

A. Biolytica. (Depressents.)

1. Plastilytica. (Mercury, Alteratives.)

2. H?matolytica. (Acids, Alkalies.)

3. Neurolytica. (Sedatives.)

B. Anabiotica. (Excitants.)

1. Plastibiotica. (Astringents.)

2. H?matobiotica. (Diffusible stimulants.)

3. Neurobiotica. (Opium, Strychnia.)

C. Agonistica. (Revulsives.)

1. Plastagonistica. (Purgatives, etc.)

2. H?matagonistica. (Irritants.)

3. Neuragonistica. (Emetics, Expectorants.)

These divisions are again subdivided with great minuteness, according to their supposed operation. And yet it will be seen that, in spite of the hard names, there is an admirable simplicity in this arrangement. So many and so various are the statements made, and so plausible the theories involved, that I cannot accord to it here a fair consideration. I must object to it, however, that there is too much generalization, and, what is more important, that many medicines may cure diseases without necessarily causing either excitation or depression or acting distinctly by revulsion. The only principles of action admitted here are these three, the same which are adopted by the disciples of Broussais. To suppose that medicines acting on the glands are only of use as revulsives, that they have no influence on the blood, and are never engaged in purging the system of peccant or morbid matter, is surely incorrect in theory. Medicines of the first class, when given in proper dose and in fit cases, are not engaged in destroying organization, nor is it invariably the case that such remedies as Mercury, Acids, and Alkalies act even as depressents, when given in moderation.

Further, the lines of distinction are too arbitrary, and drawn with too much precision. The variations in the actions of different medicines are too many and too great to be thus easily accounted for, and we do not know enough about many of them to be able to define their operation so exactly. And there is no explanation at all given here of the special tendencies of some remedies, by which we are enabled to cure a great number of disorders.

g. The Hippocratic maxim was a step towards a correct solution of the therapeutical operations of remedial agents. The humoral theory of Sydenham, and the threefold action supposed by Broussais, were further advances in the right direction. But these views were all too confined. Correct as far as they extended, they did not embrace the whole range of the subject; for it is impossible to explain by any one of them the operations of all medicines.

Biassed by the satisfactory observation which he had made of the modus operandi of particular medicines, and misled by the insufficiency of his knowledge, each of these writers was tempted to apply the view which was applicable to a certain set to all remedies alike. Once persuaded of its sufficiency, he easily found arguments by which to fortify both himself and others against any subsequent objections.

The right course lies in a combination of these various theories, embracing what is true and discarding what is erroneous in each of them, and supplying what may seem to be wanting in the whole. None of these ideas being by itself perfect, the sounder reasoners of the present day are driven to suppose that there are various different ways in which medicines may counteract, and thus cure, different diseases. This counteraction is distinct from contrary action; it may be direct or indirect; and it allows of any action in a medicine, tending to restore health, except an effect similar to the disease. Such a view was adopted by Dr. Cullen, the well known Nosologist, who lectured at Edinburgh towards the close of the last century. He discarded all special and confined views of the operation of medicines, believing that they acted in many and various ways, all of which tended to the same end-to counteract the influence of the disorder. This is well exemplified in his admirable directions for the treatment of fever, in which he enjoined the use of a number of different remedies, varied according to the nature of the case, and progress of the symptoms.[16]

Dr. Pereira, the most learned and acute of living English writers on this subject, appears, like many others, to prefer a wide explanation of this description.

On such views my own statements are based. I suppose that a disease in the blood is to be met by agents in the blood, which directly or indirectly counteract it there; that disorders, generally temporary, which depend on nervous derangement, are to be benefited by remedies which affect the nerves; and in the same way that a laxity of muscular fibre, or a failure in a secretion, should be treated by agents which especially possess the property of restoring to a right condition such parts or functions.

Concluding, then, that it is impossible to account clearly for the actions of most medicines on Mechanical or on Chemical principles, we are led to infer that their influence must for the most part be vital in its nature-that it must be such as could only be exerted in the living body. Even then we are unable to fix upon any single rule or formula which shall be capable of accounting for the actions of all at once. So it seems that the only general explanation which we can offer of the modus operandi of medicines in the cure of diseases, is to say that they operate by various counteractions.

This, then, introduces my Third Chapter.

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