It is probable that the tonic operation of quinia upon the digestive organs is chiefly direct; as it certainly possesses the property of local stimulation. This is evinced by the pain and inflammation, often followed by superficial sloughing, which result from its application, undiluted, to the surface of the skin deprived of the epidermis. The gastric and intestinal irritation, occasionally caused by it, is probably nothing more than an exaggeration of its legitimate tonic influence upon the alimentary mucous membrane. There is reason to suppose that the febriculous condition, sometimes attendant upon its action, is the result of the sympathetic extension of this irritation to the system at large. But the constitutional impression thus produced is not the normal and characteristic effect of quinia upon the system. The latter arises from the absorption of the medicine, and its direct contact with all parts of the body affected; and is in fact interfered with by any gastric irritation which may proceed from the quinia, because absorption is thus impeded. Nevertheless, it is nut impossible that the tonic effect of the medicine on the digestive organs may depend, in part, upon its entrance, through the circulation, into the interior of their tissues, and the exercise there of an excitant influence upon their nutrition.

That the active principles of Peruvian bark enter the circulation can no longer be doubted. Several experimenters have detected quinia in the blood; and it may easily be recognized in the urine, a short time after its administration, by a simple chemical test. A solution of iodide of potassium, in which free iodine has been dissolved, throws down an orange-brown precipitate from the solution of a salt of quinia. In ordinary urine no such effect is produced; but, during the use of sulphate of quinia, the application of the reagent is followed by a precipitate as soon as the system becomes affected, and as long as it continues to be so.* The quantity which passes by urine is proportionate to that administered; and, as little or none has been satisfactorily detected in other secretions, it follows that most, if not all of the salt, is eliminated by the kidneys. It is an interesting fact, moreover, that the quinia ceases to appear in the urine soon after its observable effects upon the system have ceased. The inferences deducible from these facts are, in the first place, that Peruvian bark acts on the system through the medium of the circulation, and, secondly, that its action is dynamic, that is, upon the vital properties of the parts affected, and not through any chemical combination with the tissues, which would otherwise retain the alkaloid.

But are the effects of the medicine on the system at large the same as those upon the digestive organs? Is it a general as well as local tonic? Does it stimulate the functions of the brain, heart, and other organs which it reaches by the route of the circulation, as it is admitted to stimulate the stomach? These are questions of great importance, as they are not theoretical merely, but have a strong practical bearing. There are many who agree with the Italian contra-stimulant school, in believing that sulphate of quinia is a powerful direct sedative, especially in large doses, and consequently that it is applicable to cases of high excitement, and even of active inflammation. If, as others suppose, it is essentially stimulant, this application of it is certainly not indicated, and must often be highly injurious.

I believe that it is the general impression, and it certainly is my own, that, in small doses, quinia is essentially and universally tonic. Not only upon the digestive organs, but in all the parts to which it is carried by the circulation, its effects thus administered are to excite moderately the nutritive function, and probably in some degree also that of secretion. Through its influence upon the processes by which the blood is formed, it probably tends to augment the quantity of that fluid, and to render it richer. Thus, by its own operation upon the nutrition of the heart, and through the agency of the enriched blood, it gives greater energy to the contractions of that organ; and hence the fuller and stronger pulse, not unfrequently resulting from its moderate and continued use. It does not, however, appear, like the arterial stimulants, to excite the heart immediately into increased frequency of pulsation; and, when this effect is occasionally experienced, it is probably through sympathy with the irritated stomach or brain. In all the points just referred to quinia agrees with the simple bitters. But there is another in which it materially differs from that set of tonics; I refer to its action on the brain. The simple bitters may affect that organ through the enriched blood, or possibly by directly stimulating its nutrition; but its special functions are not immediately excited, and in no degree observably interfered with. Quinia, on the contrary, acts with a special predilection on the cerebral functions; stimulating them gently, and within the limits of tonic action, when given moderately; but, in excess, producing the effects of over-excitement or irritation proportionate to the quantity used. In small doses, this influence is not evinced by any striking phenomena; but it is no doubt felt, and contributes to give to Peruvian bark that pre-eminence over other tonics which it has so long enjoyed. But discrimination is necessary in order to an accurate understanding of its operation on the brain. Resembling in some respects the stimulant narcotics, it yet differs from them in the special seat of its action. Both obey the general laws of stimulation; that is, they at first increase the normal function of the excited part, then derange it, and finally, by a continuance of their influence, diminish or suppress it. But, while the cerebral stimulants or stimulating narcotics operate more or less upon the whole encephalon, and especially upon the seat of the intellectual and emotional functions in the cerebral lobes; quinia leaves these almost unaffected, and confines its influence more especially to the centres near the base of the brain; those, namely, of sensation, and those which control the organic functions of the system. Hence we seldom see mental exhilaration, delirium, or stupor produced by quinia; while excitement, disturbance, and depression of hearing or sight, and of the reflex muscular movements of circulation and respiration, are its constant results when taken in full doses.*