THE OBSCURITY WHICH HAS ATTENDED THE OPERATION OF COMPOUND MEDICINES.
It is evident that the fallacies to which our observations and experience are liable with respect to the efficacy of certain bodies, as remedies, must be necessarily multiplied when such bodies are exhibited in a state of complicated combination, since it must be always difficult, and often impossible, to ascertain to which ingredient the effects produced ought to be attributed.
How many frivolous substances have from this cause alone gained a share of credit, which belonged exclusively to the medicines with which they happened to be accidentally administered?[[123]] Numerous are the examples which I might adduce in proof of this assertion; the history of Bezoar[[124]] would in itself furnish a mass of striking evidence, indeed the reputation of this absurd substance was maintained much longer than it otherwise would have been, by its exhibition having been frequently accompanied with that of more active articles. Monardes, for instance, extols the efficacy of the Bezoar as a vermifuge, but he states that it should be mixed with the seeds of Wormwood. Besides, in the exuberance of mixture, certain re-actions and important changes are mutually produced, by which the identity of the original ingredients is destroyed; but this subject will be introduced for discussion in the first part of the Pharmacologia.
The practice of mixing together different medicinal substances, so as to form one remedy, may boast of very ancient origin, for most of the prescriptions which have descended from the Greek physicians are of this description; the uncertain and vague results of such a practice appear also to have been early felt, and often condemned, and even Erasistratus declaimed with great warmth against the complicated medicines which were administered in his time; the greater number of these compositions present a mass of incongruous materials, put together without any apparent order or intention; indeed it would almost appear as if they regarded a medical formula as a problem in Permutation, the only object of which was to discover and assign the number of changes that can be made in any given number of things, all different from each other.
At the same time it must in justice be allowed, that some of the earlier physicians entertained just notions with regard to the use and abuse of combination, although their knowledge of the subject was of course extremely limited and imperfect.
Oribasius[[125]] recommends in high terms certain combinations of Evacuant and Roborant medicines, and the remarks of Alexander Trallianus on a remedy which he exhibited in paralysis, serve to shew that he was well acquainted with the fact, that certain substances lose their efficacy when they stimulate the bowels to excess, for he cautions us against adding a greater proportion of Scammony to it; many, he observes, think that by so doing, they increase the force of the medicine, whereas in fact they make it useless, by carrying it immediately through the bowels, instead of suffering it to remain and be conveyed to the remote parts.
In modern Europe, the same attachment to luxuriancy of composition has been transmitted to our own times: there are several prescriptions of Huxham extant, which contain more than four hundred ingredients. I have already observed that all extravagant systems tend, in the course of time, to introduce practices of an opposite kind; this truth finds another powerful illustration in the history of medicinal combination, and it becomes a serious question, which it will be my duty to discuss, whether the disgust so justly excited by the poly-pharmacy of our predecessors, may not have induced the physician of the present day to carry his ideas of simplicity too far, so as to neglect and lose the advantages which in many cases beyond all doubt may be obtained by scientific combinations. “To those,” says Sir A. Crichton, “who think that the Science of Medicine is improved by an affected simplicity in prescribing, I would remark, that modern pharmacopœias are shorn so much of old and approved receipts,[[126]] on account of their being extraordinary compounds, so as to be almost useless in some cases.”
In the year 1799, Dr. Fordyce, in a valuable paper published in the second volume of the Transactions of the Medical Society, investigated this subject with much perspicuity and success: unfortunately, however, this memoir terminates with the investigation of similar remedies, that is to say, of those which produce upon the body similar effects, and he is entirely silent upon the advantages which may be obtained by the combination of those medicines which possess different, or even opposite qualities; it must be also remembered that at the time this memoir was composed by its eminent author, Chemistry had scarcely extended its illuminating rays into the recesses of physic. Under such circumstances, I am induced to undertake the arduous task of inquiring into the several relations in which each article of a compound formula may be advantageously situated with respect to the others; and I am farther encouraged in this investigation, by a conviction of its practical importance, as well as by feeling that it has hitherto never received the share of attention which it merits. “I think,” says Dr. Powell, “it may be asserted, without fear of contradiction, that no medicine compounded of five or six simple articles, has hitherto had its powers examined in a rational manner.” If this attempt should be the means of directing the attention of future practitioners to the subject, and thereby of rendering the Art of Composition more efficient, by placing it upon the permanent basis of science, I shall feel that I have profitably devoted my time and attention to the most useful of all medical subjects. “Res est maximi momenti in arte medendi, cum, Formula in se considerata, possit esse profecto mortis vel vitæ sententia.”
PHARMACOLOGIA.|| ON THE| OPERATIONS OF MEDICINAL BODIES,| AND ON THE| CLASSIFICATIONS FOUNDED ON THEM.
“Medicos tandem tædet et pudet, diutius garrire de Remediis, Specificis, et Alexipharmicis, et cæteris, nisi eorum naturam et modum quo prosint, quodammodo ostendere et explanare possint.”
Conspect. Med. Theor.
PHARMACOLOGIA.
ON THE
OPERATIONS OF MEDICINAL BODIES,
AND ON THE
CLASSIFICATIONS FOUNDED ON THEM.
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.
| The Particular Organs of the Body may be excited into action, through four distinct and different modes of communication. | ||||
|---|---|---|---|---|
| I. | By the actual contact of the appropriate remedy. | |||
| 1. | Conveyed by absorption, WITHOUT DECOMPOSITION. | |||
| Internally. | a. | through the branches of the Thoracic duct. | ||
| b. | through the branches of the Vena Portarum.[[132]] | |||
| Externally. | c. | through the branches of divided blood-vessels. | ||
| d. | through the branches of Lymphatics.[[133]] | |||
| 2. | Conveyed by absorption, WITH DECOMPOSITION, by which one or more of its constituents are developed, and pass into the circulating current. | |||
| II. | By an impulse conveyed through the instrumentality of the nerves. | |||
| III. | By the sympathetic control exerted by the stomach on distant parts. | |||
| IV. | By the operation of contiguous sympathy, or of that which is excited by the mere proximity and continuity of parts. | |||
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.