INFLUENCE OF COLD, BELLADONNA, STRYCHNINE;

163

It is probable that the influence of cold consists in its power of reducing the amount of organic change in parts of the living body, and that consequently it would be exerted with equal efficiency over any nervous centres to which refrigeration could reach.

There is another method of operation by which cold can depress nervous activity, and this method it has in common with many other agents-I mean its sedative influence on the peripheral nervous expansion. It is thus that ice taken into the stomach diminishes, in many cases, an extreme disposition to vomit; and that, by sympathetic extension of its influence, it likewise reduces an excited action of the heart. In neitheri nstance could the effect arise, except through depression of excitement in the nervous centre.

The action of belladonna on the iris (according to its common method of use in ophthalmic surgery) illustrates even better than the distal operation of cold, this indirect control over nervous centres. An anæsthetic agent operating on the peripheral expansion of the fifth nerve produces the negation of excitement in its centre; this condition diffuses itself to the motional centre of the iris, and as excitement would have shown itself in contraction of the pupil, so the opposite nervous condition evinces itself in expansion. of that aperture. Where the reactivity of the spinal cord is very highly excited, a peripheral surface may, by the influence of belladonna, be rendered incapable of provoking reflex movements. Thus, for instance, if a frog be rendered tetanic by opium or strychnine, any contact of its cutaneous surface will produce universal spasm; if either before this poisoning or subsequent to its manifestations, one limb of the animal be plunged into a solution of extract of belladonna, no mechanical irritation of that portion of the body will cause the tetanic convulsion: the exceptional effect is the same as was produced in Dr. Mayer's experiments by division of the posterior roots; but when some other part of the surface is irritated under these circumstances, so as to procure the characteristic spinal reaction, the resulting convulsions occur in the muscles of the anesthetic limb, equally with the other muscles of the body. I need hardly point out to you the important practical applications of which this property is susceptible in diseases which consist in an exalted reactivity of the spinal cord.

Of medicines acting on the nervous centres through the blood, by way of stimulation or narcotism, there are a large number; but most of them act so complexly, that the specification of their distinctive actions is at present a matter of immense difficulty. Most of them affect, with more or less completeness, all the nervous centres ;—one series of centres, if given in their smaller doses; two or more series, if given in larger quantity; and, under the influence of the same remedy, the phenomena of centric excitement or centric depression may become variously manifest, according to the dose of the agent, and the habit of the individual.

Strychnine has already been adverted to, for its power of exciting the motional centres of the cerebro-spinal system; and this action is one of the simplest with which we are conversant, apparently not

164

TOBACCO, CHLOROFORM, AND ETHER;

extending beyond those tertiary centres, and such ganglionic centres as are subordinate to them; there is no evidence of mental affection under its use, nor are any subjective sensations excited by it.

Tobacco, perhaps, most nearly represents the opposite action; tending excessively to paralyze the motional energy of the tertiary centres; but its operation certainly extends, in the same depressive manner, to the centre of consciousness-comatose insensibility resulting from its larger doses.

As regards both these agents, it seems probable that the influence exerted by them over the heart's action (the one enfeebling, the other rendering it spasmodic) is effected by descensive sympathy, operating from the cerebro-spinal on the ganglionic system.

I have already shown how the reactive phenomena of the cord are influenced by the peripheral use of belladonna: it seems probable that analogous results would be produced, after its ingestion, by its anæsthetic or depressive action on the sensitive centres. It dilates the pupil as much when it is taken internally, as when locally applied; and as in the former manner it operates on the visual as well as the tactual centre of the eye, we find that the perception of light is impaired an effect which does not arise from its peripheral use. Any interference which its internal use may produce on the reactivity of the cord would apparently arise-not (as from tobacco) by motional paralysis, but by an anesthetic condition of the sensitive centres, forbidding the transmission of those exterior stimulations which normally excite spinal reaction. In affecting this function, it would act centrally, as I have just shown that it acts peripherally, as an impediment to the receptivity of the nervous system. In Dr. Burton's case of poisoning by belladonna, there remained, for several days after the patient's consciousness had returned, an almost complete anæsthesia. While the tertiary centres of sensation are depressed by this remedy, the centre of consciousness is remarkably stimulated, giving rise at an early period to delirium, which is characterized by the presence of extreme delusions.

Chloroform and Ether, operating by inhalation, seem to work their effects in a similar way; and the explanation which I have just given of the indirect manner in which belladonna becomes the antagonist of strychnine or of tetanus, will explain the palliative influence which chloroform is alleged to exert under similar circumstances. It does not depress the excited reactivity of the motional centres, but disables the sensitive centres from becoming media of stimulation to them.

This class of agents operates little (if at all) on the quaternary centres of the ganglionic system: these subordinate organs sympathize readily enough with the motional variations of their superordinate centres (as we see in the affection of the heart by strychnine or tobacco) but are not considerably involved in artificial anesthesia; or at least not primarily: if the anesthetic influence be intense, and the cerebro-spinal motional centres become depressed by it, then

* Medical Gazette, vol. xli. p. 1024.

unquestionably the quaternary centres of the ganglionic system may evince a similar affection.

Opium illustrates in an extreme degree the complexities of operation which obscure the pathology of narcotic medicines. Its most usual method of action in the human subject is to operate chiefly on the centre of consciousness; affecting it mainly in its receptive functions, so as to induce, first, subjective mental phenomena (dreams and imaginations) followed (or, after large doses, anticipated) by an overwhelming comatose insensibility. It rarely produces in the cerebral centres those changes which lead to active or volitional delirium; differing in this respect from alcohol and nitrous oxide. Its operation on the subordinate nervous centres is distinct and different: it excites (sometimes to an extraordinary degree) the motional centres, so that reflex-movements tend to exaggeration : witness that contraction of the pupil to a mere pin-hole which occurs under its influence: witness also the tetanic symptoms (having their origin in the cord) which it produces invariably in some of the lower animals (most of all in frogs) and occasionally in man. It is exceptional in the human subject for the spinal phenomena to be prominent after the ingestion of opium: perhaps our more highly developed encephalic centres are capable of communicating their depressed condition to the subordinate centres, in a manner which less perfect organs would fail to exhibit, and which tends to neutralize for these lower centres whatever primary influence the opium would else exert on them. Opium is not an anesthetic, except by the production of stupor. Probably the spinal centres of sensibility are among the last elements affected by it. There is one remarkable phenomenon, however, which occasionally arises from the use of opium (or morphia more particularly) and which is referable to these centres. mean the subjective sensation of itching at the skin--a sensation which is sometimes universal and intense. A few months back, I was treating a gentleman for delirium tremens: his disease resisted. the morphia-even in very large doses, and eventually yielded to chloroform; but, after each dose of the morphia, he suffered intensely from this formication, and his disordered fancy (stimulated by the subjective sensation) led him, whenever the morphia was acting, to believe and maintain that his body was covered with swarms of lice. Probably double or triple the dose here given would in this particular instance have produced anesthesia, as though belladonna had been employed: but I have never witnessed this action.

I

A most important question as regards the action of opium, and one hitherto very imperfectly solved, is that of its influence over the nutritive changes in parts;-whether that influence be exerted through the motional ganglia of the arteries (so as merely to regulate the local supplies of blood) or consist in a direct chemical control over the activity of molecular change. Of the reality of such influence-in whatever way produced, we have empirical knowledge. In surgical practice, we constantly find advantage in the use of opium, which seems referable to this head, and which leads to its employment as a prophylactic against excessive inflammatory action

in many cases of severe local injury by accident or surgical operation-after extensive lesion of serous cavities especially, where we wish to moderate the determination of blood which is likely to ensue. Many surgeons make large use of opium in this manner, employing it more or less after all capital operations; even where they are not called upon to fulfil the collateral purpose of mitigating pain.

I have said nothing of the action of narcotic medicines on the secondary centres of the nervous system; and I know very little about it. M. Flourens thinks himself able to trace some signs of cerebellar affection in the symptoms of intoxication by opium, and still more in those produced by alcohol; and various experiments which he made, by the direct application of these and other drugs to the nervous centres, furnish some confirmation of his view.

My limits will not permit me to dilate on these subjects; but the few examples I have given you may serve, at least partially, to show the sort of inquiry which is needed, and to illustrate that carefulness of selection with which narcotic medicines require to be employed.

EVACUATIVE MEDICINES CONSIDERED.

167

1

LECTURE XI.

Evacuative medicines in relation to Humoral Pathology. Critical discharges in disease; gout, rheumatism, cutaneous eruptions. Humoral disease in condition of latency, and in act of explosion. Medicinal influence over excretions. Excretive drugs having local affinities of action; diuretics; query as to effect on real act of excretion. Vicarious excretion; compensative excretion; diaphoretics in diabetes. Summary of results: Derivative medicines; medicines modifying catalysis of blood. Action of saline purgatives by way of exosmosis; pathology of ordinary constipation; natural or acquired inertness of certain drugs. Supplementary medicines.

GENTLEMEN: Within the compass of Pathology, I know of nothing so obscure and unsatisfactory as that division of the science which relates to morbid and medicinal changes in the excretory functions.

It is not difficult to say what knowledge ought to be acquired in these respects. We ought to have exact information of the changes which any drug or any disease is capable of producing in the several excretions; and we ought to possess the explanation of these changes, including (first) a knowledge of whatever chemical alterations of the blood precede, accompany, or follow them; and (secondly) a knowledge of whatever mutual relations subsist between different excretions, and how far any given variation in one particular excretion entails of necessity some corresponding variation in another. In other words-the healthy qualities of each excretion being stated by the physiologist, it devolves on the pathological chemist to fix their morbid and medicinal variations, not only simply and absolutely, but likewise relatively to one another, and to the blood. This kind of knowledge-relating to that portion of our subject which abuts on pharmacology, ought to receive its chief elucidations from the professors of the latter science. Hitherto, however, singularly little light has come to us from that quarter.

We are led to an intimate pharmaceutical acquaintance with the Materia Medica. We learn the smell of rhubarb, the tests of arsenic, the chemical incompatibilities of iron, the adulterations of quinine or sarsaparilla, and so forth. We become skilful dispensers. We know that bark very often cures ague; that copaiba frequently stays a clap; that cod-liver oil and iodide of potassium between them relieve a good many cases of scrofula; that taraxacum is sometimes useful below the diaphragm, and squill above it. And with this farrago of traditions, the misnamed science of Materia Medica has remained so contented and so stationary, that at the present moment -in the middle of the nineteenth century-we do not possess a complete medical knowledge of any single article of the Pharmacopœia.

It would be easy for one quite ignorant of medicine to predict,