Pharmacologia / Fourth American, from the Seventh London Edition

Medicinal Substances are those bodies, which, by due administration, are capable of producing certain changes in the condition of the living system, whereby its morbid actions may be entirely removed, or advantageously controlled.

In adopting this definition we intentionally exclude those alimentary substances which are more immediately subservient to the support of life, and to the repair of that diurnal waste, which the exercise of its functions so inevitably occasions.

It has been generally supposed, that substances whose application does not produce any sensible action upon the healthy system, cannot possess medicinal energy; and, on the contrary, that those bodies which occasion an apparent effect in health, must necessarily prove active in the cure or palliation of disease. Under certain limitations we may perhaps venture to assent to this general proposition; but it cannot be too forcibly or too frequently impressed upon the mind of the medical practitioner, that Medicines are frequently but relative agents, producing their effects in reference only to the state of the living frame; we must therefore concur with Sir Gilbert Blane in stating, that the virtues of Medicines cannot be fairly essayed, nor beneficially ascertained, by trying their effects on sound subjects, because that particular morbid condition does not exist which they may be exclusively calculated to remove;^[127] thus in certain states of debility, Tonics may excite the system when languid, by their sympathetic influence upon the primæ viæ, while in a robust condition of the body, the effects of the same agents may be wholly inappreciable.

The Modus Operandi of remedies, or the general principle upon which they effect salutary changes in the morbid states of the body, is involved in considerable obscurity, and has given rise to much ingenious speculation and scientific controversy. It would seem that the immediate impression of a remedy may depend upon mechanical, chemical, or vital agencies; and that the sanative impulse thus occasioned may either be Absolute, or Relative;—Primary, or Secondary;—Local, or General;—Direct, or Sympathetic;—Permanent, or Transient;—thus certain purgatives will occasion intestinal excretions in every condition of the body, and may therefore be justly considered as absolute agents; while diuretics, since they generally require for their success, a certain state of the living system, may with equal truth be denominated relative in their operation. That the obvious effect of a remedy may either depend upon its Primary, or upon its Secondary and incidental operation, will at once be apparent by inspecting the diagram which exhibits the classification of diuretic medicines; the same scheme will also shew that remedies may be local or general in their effects, and may excite an action in distant organs, either by entering the circulating mass, and being thus brought into contact with their textures;—by occasioning an impulse conveyed through the nervous system,—or by exciting a local impression upon the stomach and primæ viæ, and thus arousing their energies through the mysterious medium of sympathetic^[128] communication.

That certain bodies are capable of evading the assimilating functions, and of entering, unchanged, into the circulating current, either through the branches of the thoracic duct, or of the vena portarum, is a fact which admits of chemical demonstration; many of the alkaline salts are thus conveyed to the kidneys, and being excreted from the blood by its vessels, are to be easily detected in the urine by appropriate reagents; I have made many experiments upon this subject, and am prepared to state some results which may perhaps explain the occasional value of such bodies as medicines. Some essential oils, particular bitter principles,^[129] and certain colouring matter,^[130] seem also capable of passing the barriers of digestion, and of circulating to the remote parts of the body; Mercury, and several of the other metals, would likewise appear, under certain circumstances, to possess a similar privilege, and the former to be able moreover to facilitate the absorption of other bodies with which it may be associated, as I shall hereafter more fully exemplify.

In some instances, the medicinal body undergoes a partial decomposition by the digestive organs, in transitu, by which some of its constituents escape into the circulation, while the others are completely digested, and converted into chyle; this occurs with saline compounds into which vegetable acids enter as constituents. See Potassæ Acetas. It is also stated in the history of Diluents, that there is reason to believe that Water may under particular circumstances suffer decomposition, and transfer its elements for the formation of new compounds, furnishing oxygen to some, and hydrogen to others. There is likewise reason to suppose, that in particular conditions of the digestive functions, a remedy may be at once rendered inert by its entire decomposition.^[131]

That an impression made upon the stomach by a medicinal agent, should be the means of exciting an action in the distant parts of the machine, will not appear extraordinary when we consider how universal a sympathy and control this central organ exercises over every function of the body; imbued with exquisite and diversified sensibilities,—subjected to the first and coarsest impressions of our various ingesta,—stretched occasionally to an enormous extent by the unrestricted indulgence of appetite,—disturbed by the passions,—exhausted by volition, and debilitated by intense thinking; in short, assailed by numerous foes from without, and harassed by various revolutions from within, can we feel surprised that the aberrations of this viscus should give origin to the greater number of maladies with which we are afflicted, or that those medicinal applications should be effective that are directed for their cure, through the medium of its sympathies?

A dose of Ipecacuan, by exciting the stomach, will abate both the force and velocity of the heart in its vital motion, and affect the whole series of blood vessels, from their origin to their most minute ramifications, as is evinced by the pallor of the skin under its operation, as well as by its efficacy in arresting hemorrhage; so the brain, when disordered by vertigo, frequently derives instantaneous relief from the administration of a tea-spoonful of æther in a glass of water. The stomach however is not in every case the medium of sympathy; a substance may excite a powerful impression upon a distant part, by the instrumentality of the nerves, without any concurrence of the stomach; thus, the Belladonna, by coming in contact with the Tunica Conjunctiva of the eye, will occasion immediate dilatation of the Iris, although no other part of the system is in the slightest degree affected.

But there is yet another mode by which remedies may be made to exert a sanative effect upon particular organs of the body, through the medium of what Mr. Hunter called contiguous sympathy, and whose existence appears to depend upon the mere proximity and contiguity of parts, without any relation to the distribution of the nerves; thus it is, that relief is afforded to a deep-seated inflammation, by scarifying the nearest external surface; while we know from long experience that the thoracic or abdominal viscera, when similarly affected, receive corresponding relief from the same topical use of bleeding, blistering, or fomenting.

With respect to the Modus Operandi of medicines the following classification may be established.

And it is important to observe, that these are frequently antagonist operations, and consequently, that remedies, although they should occasion the same apparent effects, unless they act through the same medium, are not SIMILAR agents, but on the contrary, are generally medicinally incompatible with each other; for an illustration of this truth, the practitioner may refer to the observations which I have offered under the history of diuretics.

The difficulty of justly appreciating these phenomena, in every instance, has furnished a powerful objection against the validity of any classification of medicinal substances which is founded on their supposed modes of operation; and it must be acknowledged that, if we are unable to assign to remedies their primary action, or to distinguish this from their more obvious, though perhaps secondary effects, we shall frequently be compelled to place similar medicines under opposite heads, and to include those of very dissimilar characters under the same artificial division; an error which has contributed more generally to embarrass and misguide our practice than any other therapeutical fallacy, and it was the conviction of this truth which induced me to introduce the present chapter, and to impress the importance of its subject upon the attention of my practical readers.

It is probable that, in philosophical strictness, no two medicines in our Materia Medica are perfectly similar, although they recede from each other by such insensible shades of gradation that we may with practical advantage admit their parallelism; at the same time, it must be ever kept in remembrance, that those Medicines only are practically similar, whose operations have been found by experience to continue similar under every condition of the human body; and which, moreover, owe such similarity to modes of operation which are compatible with each other, and consonant with the general indications of cure.

The importance of admitting this proposition will be frequently illustrated in the sequel; and it may be observed in this place, that every classification in which it is not recognised as a leading principle, must be as imperfect in its execution, as it will be unjust and erroneous in its views.

Before I proceed to any farther discussion upon the present subject, it will be necessary to offer a synoptical view of an arrangement of medicinal bodies founded upon the basis of their operations, in order that I may be better enabled to illustrate the observations which it is my intention to introduce: for this purpose I shall present the reader with three different classifications of this kind; the first being that proposed by Dr. Cullen,^[134] and which is now admitted to rest on principles nearly altogether false, but the investigation of which will afford many useful lessons of practical importance; the second classification is by Dr. Young;^[135] and the third is that proposed by Dr. Murray,^[136] which, from its simplicity and strict conformity with the views I intend to offer, will be adopted as being the most eligible for the occasion.

With respect to the classification of Dr. Cullen, we may commence our objections by stating, that the very basis upon which it rests is a mere gratuitous assumption, viz. that certain medicines act on the fluids of the body. With the exception of a very few substances, it is now generally admitted that medicines produce their effects by acting on the living materials of which our organs are composed, and not by modifying the specific gravity, or chemical composition, of the fluids which they may happen to evacuate. The origin of this latter opinion is to be traced to the exploded notions of the humoral pathologists, and to the exclusive doctrine of the earlier chemists; for as the former recognised a depraved condition of the fluids as the source of every disease, so did the latter imagine that every remedy operated by producing a chemical change upon its composition; and the remedial value of a medicinal substance was estimated by its effects upon inert matter. Thus were experiments made with different substances upon the blood, and other fluids of the body, in order to deduce, from the results, the nature and extent of their powers as agents upon the living frame; for instance, the spirit and salt of hartshorn, as they were found to render the blood more fluid, when added to it, out of the body, were indiscriminately administered in almost every complaint, with a view to dissolve that “lentor of the fluids” which was regarded as the more general source of disease. For similar reasons, a tribe of medicines were introduced into practice under the title of Antiseptics, for the prevention of a process which very probably never takes place in the living body: the powers of these supposed agents were, as usual, inferred from their effects in resisting and preventing the putrefaction of dead matter.

Nor is the distinction assumed by Dr. Cullen, between the action of remedies on the Simple and Living solids less hypothetical. Tonics and astringents may certainly exert a beneficial effect upon the animal fibre, but not by any immediate action on its materials, but through the agency of its living principle.—“Medicamentum non agit in cadaver.”

The classification of Dr. Young, although it presents many points of interest and value, is not altogether free from objection; his classes in some instances are perhaps unnecessarily sub-divided, without a sufficient regard to the primary and secondary operations of the substances which they include. The arrangement of Murray has been adopted in the present inquiry, not as being less objectionable, in a general point of view, but as one which from its simplicity, is better calculated, as a frame-work, if I may so express myself, for the display of those particular facts, the knowledge of which I consider essential for the successful administration of medicinal agents, and for the full comprehension of those practical doctrines which it is the exclusive object of this work to inculcate.

Dr. Murray observes that, in this arrangement, he places in the first division those substances which exert a GENERAL STIMULANT operation on the system. Of this there are two sub-divisions, the Diffusible and the Permanent; the former including the class of Narcotics, with which may be associated, as not very remote in their operation, the class of Antispasmodics; the latter comprising two classes, viz. Tonics and Astringents. Through these there is a gradual transition from the most highly diffusible stimulant, to those most slow and durable in their action.

A second division comprehends Local Stimulants, those, the action of which is determined to particular parts of the system. Such are the classes of Emetics, Cathartics, Emmenagogues, Diuretics, Diaphoretics, Expectorants, and Sialogogues; with which may be associated the classes of Errhines and of Epispastics, founded on direct local application.

The remaining classes include substances which do not operate according to laws peculiar to the living system. To one division may be referred those, whose effects depend on the Chemical changes they produce in the fluids or solids; the classes which may be established on this principle are Refrigerants, Antacids, Lithonthriptics, and Escharotics. To another division belong those, the operation of which is purely Mechanical, as Anthelmintics, Demulcents, Diluents, Emollients, and certain Laxatives.

Under the above classes, says Dr. Murray,^[137] may be comprehended all those substances which are capable of producing salutary changes in the human system, and which are used as remedies. I have stated my reasons for adopting this as a general basis of classification, although I shall deviate very considerably in the subordinate divisions of the plan, in the hope of establishing some distinctions that may tend to practical utility.

The four classes comprehended under this first division, are Narcotics, Antispasmodics, Tonics, and Astringents.

Although these remedies differ very essentially in the degree and permanence of their action, as well as in the character of their apparent effects, yet, as it is conceived that their primary operation is stimulant, they are considered as possessing sufficient general similitude to sanction their arrangement under one comprehensive division.

NARCOTICS.

Substances which, in a moderate dose, occasion a temporary increase of the actions of the nervous and vascular systems, but which is followed by a greater depression of the vital powers than is commensurate with the degree of previous excitement, and which is generally followed by sleep.

The relative intensity of these primary and secondary effects varies in the different narcotics,^[138] and even in the same narcotic in different doses; in some cases, especially if the quantity administered be considerable, the symptoms of diminished sense and action follow so immediately, that the previous stage of increased action is very obscure, or not in the least perceptible, while in other cases, the operation of the substance is more particularly directed towards the heart and arteries, and syncope succeeds its exhibition. These facts have led many physiologists to deny the stimulant nature of these bodies, and to consider their primary operation as one of a depressing kind, whence they have bestowed upon them the name of Sedatives; in referring to the classification of Cullen and Young, we shall find that the arrangement of these substances has been directed in strict conformity with such a view of the subject; but it may be asked, how the increased excitement and exhilaration which so obviously follow the use of these bodies, in small doses, can be reconciled with that theory which considers them as absolutely and primarily sedative? In order to combat an argument so fatal to his hypothesis, Dr. Cullen summons to his aid the potent intercession of his tutelar deity, the Vis Medicatrix, a power which he supposes to preside over our living body, and with anxious vigilance, to resist the invasion of every thing that is noxious, or hostile to its health and well being; with such assistance it was not difficult to explain any paradox in physiology, and the anomalies attending the agency of narcotic medicines were accordingly, in the school of Cullen, easily reconciled with the views of a favourite theory. He supposed that whenever a sedative was applied in a moderate dose, the Vis Medicatrix took the alarm, and excited all the powers of the system, in order to throw off the noxious application, and that thus indirectly arose those peculiar symptoms of increased action; but when the dose was more considerable, he contended that the preserving power of the system was silenced, and unable to offer any salutary resistance, and consequently that universal depression immediately followed; but there is no direct evidence in support of the existence of such a power, and still less of its influence upon such occasions; it is far more philosophical to refer the operation of narcotics to a peculiar stimulating power, remarkable for the extreme rapidity with which it exhausts the energy of the nervous system. No one will deny the stimulating powers of alcohol, and yet a very large draught of this liquor will occasion extreme exhaustion without the occurrence of any signs of previous excitement; nor will any one be disposed to question the depressing influence of opium, and yet small doses have enkindled excitement and sustained the powers of life, under circumstances of extreme and alarming exhaustion.^[139]

From the celerity with which narcotics produce their effects, it is reasonable to suppose that they act upon the nervous system through the sympathetic relations of the stomach, although in some instances it is highly probable that these bodies are actually absorbed into the circulation; I am inclined to think that this occurs with opium, as death is accelerated in cases of persons poisoned by it, by the adoption of those measures which are best calculated to promote its absorption: (see Opium.) A still more striking proof is furnished by the fact of opium, when externally applied to ulcers, producing all its constitutional effects, such as costiveness, head-ache, nausea, &c. Whether the effects of spirituous potations are to be attributed to the introduction of alcohol into the blood, or to the sympathies existing between the stomach and brain, is still a question of doubt. Dr. Cooke^[140] relates a case, on the authority of Sir A. Carlisle, of a person who was brought dead into the Westminster Hospital, in consequence of having drank a quart of gin for a wager, and that upon examination, a considerable quantity of a limpid fluid was found within the lateral ventricles of the brain, distinctly impregnated with gin. I very well remember the case, for it occurred during the period that I held the situation of Physician to that hospital, but it is very doubtful whether such an absorption occurs under ordinary circumstances. We well know the facility with which certain odorous bodies enter the circulation, and are developed in distant organs; it is therefore very possible that the apparent odour of the gin, which has been sometimes recognized in the secretions, may depend upon the presence of the flavouring ingredients, independent of the alcohol?

At one period, substances supposed to possess narcotic virtues were placed about the bed to obviate watchfulness; the plant Anethum, or Dill, was very commonly suspended over the head for such a purpose, while in modern times the Hop has been introduced into the pillow.

In concluding the history of Narcotics, it may be observed, that there is, perhaps, no class of medicinal bodies, the individuals of which are less disposed to bend and conform to an artificial arrangement; each would seem to have its own particular mode of operation, and to affect sensibility in its own peculiar manner; and hence the practitioner will often find that, after the failure of one narcotic, the administration of another will induce sleep.

Substances which have the power of allaying the inordinate action of muscular structures, and of assuaging pain, without occasioning that state of insensibility which characterises the operation of narcotics.

There are certain medicinal bodies which would appear to exert a specific control over spasmodic action, from whatever cause it may have originated, such are Assafœtida, Galbanum, Musk, Castor, Ammonia, Valerian, &c. To such remedies the term antispasmodic more exclusively belongs, but in a more general view of the subject we must admit that this class branches, by indefinable gradations, into narcotics and tonics; for since spasm may be connected with the most opposite states of the body, it is very evident that many of the individuals included in the class of antispasmodics, can only be relative agents: spasm, for instance, may arise from excessive irritability, as from teething, wounds, worms, &c. in which case a narcotic would prove beneficial; or it may depend upon a state of general debility, the proper remedy for which would be the administration of an Aromatic Stimulant, or the assiduous exhibition of some permanent tonic.

TONICS.

Substances, whose continued administration gives strength and vigour to the body.

It is very justly admitted, that a state of permanent tension in the fibres of the body is necessary for the existence of life, and that any undue departure from such a condition is followed by debility. Thus, Sir Gilbert Blane observes, that no muscle, whether voluntary or involuntary, can act unless its fibres are previously in such a state, that if divided they would shrink by their own resiliency, leaving an interval between the cut extremities; the same may be said of the vascular system in all its ramifications, in order to give play to their contraction in grasping and propelling their contained fluids. It appears that there are certain medicinal bodies that have the power of affecting this state of tension, and when their effects contribute to its restoration, they are properly denominated Tonics. We are not, however, to consider them as producing such a change by any mechanical operation upon the matter of which the fibre is composed, but by a direct action upon its living principle; it seems probable that certain poisons may thus produce sudden death by their agency on the vital principle, by which the tension of the heart and whole arterial system is immediately relaxed. In this point of view, Tonics, like the other remedies which we have described, may be relative or absolute in their operation. Venesection, purgation, or whatever will, under certain conditions of the body, occasion a salutary change in its vital powers, may produce a corresponding alteration in the tension of its fibres, and consequently fall under the denomination of a tonic remedy: but independent of the state of the body, there would seem to be certain substances that act as specific stimuli upon the living fibre, and are in certain cases indispensable for the maintenance of its healthy tone; such are vegetable bitters, which produce a powerful effect upon the digestive organs, and by nervous sympathy, upon the rest of the system. Bitter Extractive,^[141] seems to be as essential to the digestion of herbivorous, as salt is to that of carnivorous animals; it acts as a natural stimulant, for it has been shewn by a variety of experiments that it passes through the body without suffering any diminution in its quantity, or change in its nature. No cattle will thrive upon grasses which do not contain a portion of this vegetable principle; this fact has been most satisfactorily proved by the late researches of Mr. Sinclair, gardener to the Duke of Bedford, which are recorded in that magnificent work, the “Hortus Gramineus Woburnensis.” They shew, that if sheep are fed on Yellow Turnips, which contain little or no bitter principle, they instinctively seek for, and greedily devour any provender which may contain it, and if they cannot so obtain it they become diseased and die. We are ourselves conscious of the invigorating effects of slight bitters upon our stomach; and their presence in malt liquors not only tends to diminish the noxious effects of such potations, by counteracting the indirect debility which they are liable to occasion, but even to render them, when taken in moderation, promoters of digestion. The custom of infusing bitter herbs in vinous drinks is very ancient and universal; the Poculum Absinthiatum was regarded in remote ages as a wholesome beverage, and the Wormwood was supposed to act as an antidote against drunkenness. The Swiss peasant cheers himself amidst the frigid solitude of his glaciers, with a spirit distilled from Gentian, the extreme bitterness of which is relished with a glee that is quite unintelligible to a more cultivated taste. With regard to the natural use of Bitter Extractive, it may be laid down as a truth, that it stimulates the stomach,—corrects putrefying and unwholesome nutriment,—promotes tardy digestion,—increases the nutritive powers of those vegetable substances to which it is united,—and furnishes a natural remedy for the deranged functions of the stomach in particular, and through the sympathetic medium of that organ, for the atony of remote parts in general; and I shall hereafter shew, that in its medicinal applications it certainly imparts additional activity to many remedies, while it renders the stomach and system more susceptible of their salutary energies. As an essential ingredient in the provender of herbivorous animals, it may I think be admitted as a fact, that its importance is in an inverse ratio with the nutritive powers^[142] of the food, and we accordingly find, in conformity with that universal scheme of self-adjustment and compensation, which influences all the operations of nature, that cultivation, which extends the nutritive powers of vegetable bodies, generally diminishes their bitterness in the same proportion; the natural history of the Potatoe offers a good illustration of this fact, for the roots of this useful plant which have been so greatly improved by culture, are in their wild state both small and bitter.^[143] Gummy matter, which seems to result from the first change of the sap, is undoubtedly rendered more digestible and nutritive by the presence of a bitter; pure gum is not very much disposed to yield to the assimilative functions; “it frequently passes through the bowels,” says Dr. Chapman,^[144] “very little changed, as I have witnessed a thousand times.” We see therefore the value of the bitter principle, in the economy of the Lichen Islandicus, which is intended as the food of animals in northern latitudes; we are told that boiled linseed constituted the sole diet of the people of Zealand during a scarcity of long continuance, on which occasion, symptoms of great debility occurred, attended with those of dyspepsia; so again Professor Fritze, in his Medical Annals, states that vegetable mucilage, when used as a principal article of diet, relaxes the organs of digestion, and produces a viscid slimy mucus, and a morbid action in the primæ viæ, an effect which analogy shews might be obviated by the addition of bitter extractive. For the same reason animals that feed in marshy lands, on food containing but little nourishment, are best defended from the diseases they are liable to contract in such situations by the ingestion of bitter plants.^[145] Upon these occasions nature is very kind, for the particular situation that engenders endemic diseases is generally congenial to the growth of the plants that operate as antidotes to them.

I have offered these views upon the subject of Bitter Extractive, from a conviction that they will essentially contribute to the establishing of just and philosophical notions, respecting the necessity and modus operandi of many vegetable tonics.

As the action of tonics is gradual, so their operation is not followed by that exhaustion consequent upon the use of diffusible stimulants.

The substances which compose the class of tonics are derived from the vegetable and mineral kingdoms; those of the former are generally bitter, and produce their effects by a primary action on the stomach, and are not absorbed into the circulation, as experiments upon Bitter Extractive have most fully demonstrated; those derived from the mineral kingdom, comprehending several of the metals, appear in some instances to pass into the circulation, although several of them, like the vegetable tonics, act primarily on the primæ viæ; I apprehend this observation applies to the nitrate of silver, which certainly possesses considerable powers as a tonic in certain cases of dyspepsia, for which it may perhaps be indebted to the bitterness which distinguishes it.