Physiological Action of Quinidine. - There is every reason to believe that this corresponds exactly in every particular with that of quinine. Baxter ranks quinidine just equal to quinine as a protoplasm-poison; and in all other respects it appears to behave precisely like it in the animal organism.

Physiological Action of Cinchonidine. - The great powers and activity of this alkaloid have only of late been appreciated. As a protoplasm-poison, and probably in every other physiological relation, it comes next to quinine and quinidine, and decidedly above cinchonine.3

One additional remark may be made before closing this account of the physiological action of the bark-alkaloids. It has been mentioned that bark itself in large doses has occasionally induced sexual excitement; and there is some reason to believe, though the matter is not cleared up, that each of the four alkaloids is capable of producing this effect under certain conditions.

Therapeutic Action. - The curative effects of quinine and the other alkaloids of cinchona are manifold, and may be distributed into four chief divisions; (a) Antimiasmatic, (β) Antiseptic, (y) Antiphlogistic, and (8) the special actions on morbid conditions of the nervous system. Probably indeed there should be a fifth class including the (ε) so-called oxytocic action of quinine on the uterus, and some other more doubtful examples of its immediate action on muscular viscera.

a. The antimiasmatic action of cinchona alkaloids, by means of which they put an end to the morbid processes induced by the so-called paludal poison, is still the most interesting as it was the most anciently known therapeutic effect of bark. It is a fact as familiar to the public as to the medical profession that intermittent and remittent fevers yield promptly to the influence of bark or quinine; but it must be added that the modus operandi cannot be stated more than conjecturally, though it is now years since this remarkable specific effect was made known to European physicians.

The most probable theory is that which has been advanced chiefly by Binz and his followers, namely, that the paludal poison consists of, or is conveyed by, low organisms which enter the body, and increase and multiply in the blood; and that the anti-miasmatic action of quinine consists in its restraining power over the development and multiplication of these organisms.

The fact that quinine has such a power over the lowest organisms is now so amply demonstrated that there is no occasion to reopen that part of the question. But the dependence of malarial poisoning upon the entrance of such bodies into the human organism is still among the vexed questions of pathology; and while increasing numbers of observers are inclined to affirm it, I see no grounds even now for a more positive statement than the following, by Nothnagel, three years ago: "How far these researches with their concordant results - that quinine checks putrefaction and fermentation by destroying infusoria and fungi - will be able to be utilized for pathology, is still uncertain. It is evident that at a time when people are everywhere discovering infusoria and fungi in pathological processes, it is tempting to apply Binz's researches to explain the value of quinine in malarial, puerperal, septicaemic, and (typhous) febrile processes, but this is impossible so long as the fungoid theory of these affections rests upon so unstable a basis as at present."

1 Vide Buchanan Baxter: Loc. cit.

2 It is a singular circumstance that, just as cinchonidine is obtaining its due recognition as one of the most powerful alkaloids, evidence has been procured which shows that the Countess of Chinchon (whose cure from intermittent fever originated the name "cinchona") was probably treated with a species of bark particularly rich in cinchonidine.

Without venturing to reverse this judgment, it may be admitted, however, that there is an increasing probability that the parasitic theory of the above-mentioned disorders will receive a more satisfactory confirmation in the future. But it must be remembered that very able pathologists are entirely opposed to the germ-theory of zymotic diseases; and those who wish to see the opposite view very ably presented in its most absolute form may be referred to Dr. Bastian's arguments.1

It is at least uncertain whether the germ-theory will not have to be modified in the sense of supposing that neither infusoria nor fungi, but the rapidly multiplying matter of human origin for which Beale pleads, or the analogous substances which are imagined in the graft-theory of Dr. Ross, are the true elements of infection. But in the latter case there would still be room to suppose that Binz's explanation would apply, for it would still be probable that the alkaloid acts curatively by its power to limit protoplasm formation.

We have now to consider the practical employment of quinine in the malarial fevers. The simplest case is that of the typical Intermittent fevers in the acute stages; but there are conflicting opinions as to the best method of administration even in these diseases. Probably almost any method which insures the daily absorption into the blood of some five or six grains of quinine would, in the end, cure any not extremely severe case of intermittent fever; but strong statements have been made by different authors in favor of different modes of distributing the dose. By some it has been laid down that we ought to give a single large dose of twenty or even thirty grains immediately before an attack is expected; others say that a smaller dose should be given, but either immediately after a paroxysm, or even while the final (or sweating) stage of the fit still lasts. Others, again, advocate the continuous use of large doses, both during the paroxysm and also during the periods of intermission; while another, and this perhaps the largest group of authorities, maintains that quinine should be given only during the intermissions, and then in repeated small doses (two to four or five grains or less).