This section is from the book "A Treatise On Therapeutics, And Pharmacology Or Materia Medica Vol1", by George B. Wood. Also available from Amazon: Part 1 and Part 2.
There can be no doubt that the active matter is absorbed, and operates through the circulation. This is proved by an experiment of Ver-niere, who found that, when a ligature was applied around the leg of an animal so as to check the flow of blood in the veins, but not in the arteries, and extract of nux vomica was introduced into a wound in the foot, blood taken from the vein proceeding from the wound towards the ligature, and injected into the veins of another animal, caused the death of the latter with the characteristic symptoms of poisoning by this drug The same inference may be drawn from the facts that strychnia produces its peculiar constitutional effects, to whatever part capable of absorption it may be applied, and that the rapidity with which these effects occur is proportionate to the facility of absorption in the part. Thus, in contact with the lungs, it operates more quickly than when swallowed, and in the stomach more quickly than when applied to the skin. Dr. Christison killed a dog in two minutes by the injection of one-sixth of a grain in alcoholic solution into the cavity of the chest. Inserted into a wound it operates still more quickly; and, when injected into the veins, its effects are almost instantaneous. In all these instances, too, the effects are identical; proving that, in all, the blood is the vehicle by which the poison is conveyed to the part affected. Besides, Dr. A. I. Spence, of Edinburgh, has proved by experiment that strychnia is wholly unable to act by means simply of nervous communication. (Ed. Med, Journ., July, 1866, p. 45).
The medicine, when absorbed, has not been found to produce any change in the blood itself; and the phenomena of its action evince that its influence is exerted mainly at least upon the solid tissues. Upon these it seems to operate, in very small doses, as a moderate stimulus of the tonic character, closely resembling the simple bitters in the modification of the functions it induces. But it may be inferred, from its effects in larger doses, that even this tonic influence is exerted specially upon the nervous centres; and important therapeutic inferences may be deduced from this view of its action.
When given so as to produce the peculiar effects above enumerated, all the phenomena go to show that it is mainly upon the nervous centres of the spinal marrow, including the medulla oblongata, that the medicine operates. The functions of the brain are often wholly unimpaired, even when the spasms are frightfully violent; and the division of the spinal marrow near the occiput, or even the decapitation of the animal, does not prevent them. That it is not upon the muscles directly that the medicine acts may be inferred from their simultaneous contraction, and simultaneous relaxation, showing that the influence modifying their condition flows from a common source; and this can only be in the nervous centres which preside over them. Besides, .Matteucci observed that, after death from strychnia, the muscles could be made to contract by the direct application to them of an electric current, but refused to respond to the same stimulus applied to their nerves; the latter having been exhausted of their excitability by the stimulus of the poison, while that of the former remained unimpaired. Another fact confirmatory of the special spinal influence of nux vomica, is the almost exact resemblance of its poisonous phenomena to those of tetanus, which is generally admitted to have its essentia] seat in the spinal marrow.
But what is the nature of the action thus shown' to have its seat in the medulla spinalis? It appears to me obviously to be merely an excessive excitement, or, in other words, irritation of the nervous centres of this structure, extended no doubt thence to the nerves proceeding from them. The first effect is to exalt the sensitiveness of these centres
Hence, even before the spasmodic movements commence spontaneously, they may often be induced by the slightest impressions upon the surface, such as would ordinarily produce no effect. An increase of the stimulus irritates the centres into excessive action, without the aid of any additional exciting cause; and the characteristic spasms now occur with a violence proportioned to the central irritation. But in this, as in all other cases of over-excitement, the excitability itself is more or less rapidly exhausted; and, if death be not produced by the interference of the spasms with some vital function, there follows a condition of greater or less prostration of the spinal power, and consequently of depression in the functions dependent upon it. There is reason to believe that death is not always induced by the rigid immovability of the respiratory muscles, rendering breathing impossible, and thereby inducing asphyxia; for it has been found that respiration, artificially sustained, does not prevent the fatal consequences of poisoning with nux vomica. The exhaustion of the whole medulla oblongata by its over-excitement will explain the result. It has been conjectured that among the causes of death may be a direct influence of the poison on the heart, either causing a spasmodic contraction of that organ, or exhausting its excitability through previous stimulation. In support of this opinion, an experiment of M. Briquet may be adduced, who, having injected extract of nux vomica into the veins of a dog, observed the first effect to be considerably to elevate the haemadynameter of Poiseuille, which subsequently fell lower and lower until death, indicating first an augmentation of the heart's force, and afterwards a reduction with exhaustion of its excitability. After death, the heart could not be excited to contraction. (Briquet, Trait. Therap. du Quinquina, p. 87.) It may be that there is a conjoint excitant action upon the respiratory nervous centres and the heart, followed by a conjoint failure of power in both. It has been supposed that the sympathetic nervous centres are affected in like manner with those of the spinal marrow; but we have no sufficient evidence upon this point. That the nerves conveying the spinal influence to the muscles participate in the irritation and subsequent depression or exhaustion of the centres, would seem to be shown by the experiment of Matteucci before referred to, which proves that at least they lose the susceptibility to galvanic influence, while the muscles themselves remain sensible to it.
It is probable that the influence of nux vomica extends to the whole spinal marrow, including the medulla oblongata; for there is no muscle in the body, supplied from that source, which is not liable to be thrown by it into spasm.
Some suppose that the medicine acts on the cerebellum; and it has been noticed, by several observers, that this structure occasionally exhibits post-mortem evidences of having suffered in cases of poisoning. With those who believe that the cerebellum is the special seat of the sexual propensities, the excitation of the genital organs which has been occasionally noticed under the influence of nux vomica, will afford further proof of the correctness of this supposition.
Though the cerebral lobes are seldom affected by this agent, and per* baps never by a direct influence, yet the sensorial region at its base often participates in the irritation, as shown by the frequent itching and tingling sensations experienced, and the occasional occurrence of irregularities of sight and hearing, contraction or dilatation of the pupil, etc. These may be owing either to a direct action of the medicine, or, what is quite as probable, to a radiation of the original and direct spinal irritation from the medulla oblongata to the contiguous parts of the cerebrum.