These systems are first excited and then paralyzed by antimony in varying degree according to the dose and the amount of gastric irritation. Restlessness and pain may be at first marked with general tremor and spasmodic contraction of the muscles, either of the abdomen, the jaw, the oesophagus, or extremities, especially of the hands (case of Mrs. Prichard, etc. - cases by Orfila, Elliotson, etc.).

In animals, reflex sensibility is much diminished (Radziejewski), and some degree of motor palsy occurs: these effects, so far as they are central in origin, are spinal rather than cerebral, for they occur equally when the cerebral centre is separated.

They have not been so marked in man, but great muscular prostration is quickly induced, and profound collapse is a characteristic symptom of antimonial poisoning: in some exceptional cases it has been more marked than any irritant symptoms.

There may be temporary loss of consciousness and semi-narcotism (case of Mr. Bravo), or convulsion, and later delirium (Orfila), but usually the mind remains or becomes clear before death.

Fatal Dose

The minimum fatal dose for an adult may be stated at 2 gr.; for a child, 3/4 gr.

The post-mortem appearances have been sufficiently indicated. We need only note further confirmatory evidence of the power of antimony to produce fatty degeneration in the experiments of Salkowski, who found this change in the viscera of animals after adding 8 to 15 gr. per diem of an antimonial compound to their ordinary food.

Theory Of Action

There has been much discussion as to whether the vomiting and purging which are produced by antimony are due to direct gastro-intestinal irritation, or are secondary to an influence exerted on the nerve-centres (medulla oblongata) by the drug after absorption. The former view was commonly accepted until Majendie's experiment of substituting in an animal a bladder for the natural stomach, and then causing vomiting by intravenous injection of antimony. Such an experiment seemed to prove that emesis was effected through the nerve-centres independently of the stomach; and besides this, the persistence of the nausea seemed to indicate more than an ordinary (mechanical) irritation. Chouppe has also concluded from recent experiments that although antimony may act by such irritation, it more usually acts after absorption. He divided the vagus nerve in dogs; and after subsidence of the retching from the operation, injected antimony into the cellular tissue or veins, and vomiting followed as usual: as an experiment for contrast, he injected in other dogs emetine, and when the vagi were divided this caused no vomiting (Abstract, Lancet, ii., 1874, p. 532). Broussais and others, however, always maintained the earlier views as to local irritation, and they are further supported by the following evidence: - (1) Emesis has occurred before any antimony could be detected in the blood (Mayerhofer). (2) In several instances nearly the whole of a dose of antimony has been recovered from the vomited matters - implying that very little, if any, absorption could have occurred before vomiting (Radziejewski). (3) In almost all fatal cases, marked congestion or signs of irritation have been found in the stomach after death, and this even when the drug has been given by the veins or other channels. It has clearly been proved that elimination occurs from the gastric membrane under such circumstances, and it is probable that, in Majendie's experiment, the drug was eliminated by the pharynx and by the intestine, and produced vomiting just as if introduced into the natural stomach (Hermann, Grimm, Brinton, Richardson). (4) A smaller dose will produce vomiting when given by the mouth than when given by the veins; this seems a crucial experiment on the point, and, although an opposite statement has been made by some observers, it has been verified by Hermann, Grimm, Kleimann, etc., and it is agreed, of course, that general symptoms occur also after, and in consequence of, absorption, and that nausea and prostration are prolonged in consequence of such absorption.

Another question is, whether the deeply depressing effects of the drug are due to a special "contra-stimulant" action (Rasori), or whether they are only secondary to the emetocatharsis (Broussais). I must conclude also on this point, that without denying a depressant effect after absorption, and poisoning of the nerve-centres, the muscular tissue, etc., yet the early depression and collapse depend rather on the gastric irritation, the nausea, and the vomiting, and are due to reflex action on the sympathetic and pneumogastric centres. We know that nausea from any cause is accompanied with prostration, faintness, chilliness, and pallor, and antimo-nial nausea causes the same symptoms in a similar manner, without invoking any speciality in its action (Gubler).

Tolerance, we may explain in some instances, perhaps, by the fact of only partial absorption occurring, e.g., through deficiency in the gastric secretions during fever; but this will not explain it so completely as some have supposed, because the induced feebleness of circulation and respiration, and occasional occurrence of organic lesions, prove that sufficient absorption must have taken place to cause the ordinary effects.

A more reasonable explanation is to be found in the impaired nerve-condition, and especially the diminution of reflex excitability in the subjects of "tolerance."

We may say that all those in whom it is evident at once (so that they bear "Rasorian" doses of one or more drachms without any pain or vomiting), are either suffering from some neurosis of stomach or vagus, or from some grave malady, as pneumonia, which clearly lowers their vital power: and in those persons in whom tolerance has been slowly induced by the gradual increase of small doses, we may presume that antimony has exerted its known power of diminishing reflex activity, and has thus reduced the patients in this respect to the condition of invalids, even if in other respects convalescent.

Moreover, in many cases of tolerance, though there has been no vomiting, yet diarrhoea has occurred, and the absence of vomiting, which is a complex act, may simply mean that reflex nerve-power is too much impaired for its production, diarrhoea being a simpler process.

In women and children, reflex nerve-activity is higher than in the average man, which fact would, according to the previous hypothesis, explain why tolerance is less readily induced in them.

Synergists

Other emetics, such as ipecacuanha, and other purgatives, such as calomel, increase the effects of antimony. Sedatives, such as bleeding, and more especially digitalis and veratrum, have an allied action: also other medicines which under certain circumstances quiet febrile excitement, as quinine in full doses, arsenic, bromides, citric and tartaric acids.

Antagonists And Incompatibles

Aromatic, alcoholic, and other diffusible stimulants counteract the depressant effects of antimony. Narcotics, and especially opium, hinder its special action (Rasori) - Gubler, indeed, calculates that opium lessens its power by one-half, and considers it much better to give a half-dose in any case, or to give the narcotic separately, than to combine such antagonists. Graves, however, has proved a clinical value in the combination, and Laennec found antimony better borne when conjoined with opium and aromatics.

Cold acts as a partial preventer of vomiting, and warmth, of diarrhoea.

Mechanical antidotes are such as oil, thickened milk, and mucilaginous substances: and tannin, in all its forms, is a powerful chemical antidote: decoctions of oak and cinchona bark, gall-nuts, strong tea, etc., may be used, and life has been saved by these agents in apparently hopeless cases of poisoning.

Therapeutical Action (External)

The ointment acts as a strong local irritant, and was much employed when counter-irritation was more highly esteemed than it is at present. The pustulation caused by antimony is more painful, but perhaps more permanent in its good results, than that produced by croton oil.