Absorption And Elimination

Soluble compounds of antimony, such as tartar emetic, are readily absorbed, especially by mucous membranes, and they circulate in the blood, either unchanged or as albuminates. The infant at the breast may be affected by them through the mother, and they may be detected in the different secretions during life, and in the viscera, especially the liver, kidneys, and intestines, after death.

The degree of absorption naturally varies with the preparation used, the dose, and the state of the stomach. Metallic antimony in powder, the oxide, and the sulphuret are absorbed to some extent, but much less freely than the potassio-tartrate, which is itself more completely absorbed, and acts more powerfully, if acid wines or fruits are taken at the same time (Trousseau). Large doses are usually vomited soon, and before much absorption has occurred; but if taken with, or shortly after, food vomiting is delayed, and a poisonous amount is more readily taken up into the circulation. This does not conflict with the statement made by Trousseau, that if a patient be living well, irritant effects, such as vomiting and purging, are more likely to occur from medicinal doses of antimony, while spare diet favors the production of constitutional effects, such as sedation and increased secretion, without so much gastric irritation. This fact has been explained by the presence of more chlorides in a full diet (as compared with a spare one), leading to the formation of more of the irritant chloride of antimony (Mialhe); but Bellini found that no such decomposition occurred with artificial gastric juice at the temperature of the body, and the hypothesis of Mialhe has not been accepted.

If the mucous membrane of the alimentary tract be inflamed, the irritant effects of antimony are proportionately severe.

Absorption may occur through the skin, though not readily while the epidermis is intact. After frictions with antimonial ointment vomiting has occurred, and the drug has been found in the urine (Coze: Bulletin de Therapeutique, 1869).

Antimony is eliminated by the kidneys, the skin, by the mucous membrane of the bronchi, and (mainly) by that of the intestines, and by the intestinal glands. Orfila recorded its special determination to the lungs, and Millon to the liver (Annales d' Hygiene, vol. xxxvi.). An important fact is that elimination occurs by the intestinal tract, even when the drug has been given by the veins, the rectum, or any other channel (Hermann, Richardson, Brinton, and others, Lancet, i., 1856). The amount passed out by the kidneys, and probably by the other glands, varies at different times in the same individual, for Mayerhofer, while continuing to take the drug, found it only occasionally present in the urine (Heller's Archives, 1846).

The time of its remaining in the system has been variously estimated. According to Taylor, it passes wholly from the stomach within a short time, and may then be found in the liver, the kidneys, and spleen, and in smaller quantities in the blood. After a few weeks, all traces have disappeared from these tissues, but some may be found in the fat and the bones; generally, elimination is complete in from twenty to twenty-five days, but according to Millon and Layran, the drug may be found in the liver and intestines four months after administration (loc. cit.).

Physiological Action (External)

The watery solution of tartar emetic applied to the skin acts as a slight irritant, producing redness, but the ointment when rubbed in acts more powerfully, causing inflammation and pustulation; caries of subjacent bone has even been traced to it. The pustules produced by antimony are very painful; they are irregular in size and shape, but being often umbilicated, resemble those of variola: they mature about the fifth day, forming scabs; sometimes they slough and leave scars. Individuals vary much in susceptibility to the ointment, and during fever, or severe visceral inflammation, pustulation is not easily induced.

It has been stated that alkalies mixed with antimonial salves prevent their pustulating effect, and also, but incorrectly, that freshly-blistered surfaces do not pustulate because of the alkalinity of the serum: on the other hand, acids increase the effect (M. Coze, loc. cit.).

If concentrated solutions be taken by the mouth, they are liable to cause inflammation and even aphthous ulceration about the gums, fauces, and oesophagus, so that an "antimony sore throat" has been described, and its accompanying salivation and dysphagia may be very severe. Conditions much resembling those of diphtheria have also occurred (Medical Times, i., 1846), but are not often met with under the present more cautious use of the drug.

The prolonged contact of antimony determines in the intestinal mucous membrane local phlegmasiae analogous to those already described as occurring in the skin; Trousseau verified this by post-mortem examinations.

Physiological Action (Internal)

Circulatory System

Under the influence of antimony, the blood is altered in its chemical characters (Richardson), but in a manner not yet well understood; it may certainly become impoverished from destruction of red, and increase of white corpuscles (Schmidt), just as under the action of arsenic (Koschlakoff): in cases of poisoning by the drug, it has been found more fluid and less coagulable than normal, the amount of fibrine being diminished.

A prominent symptom of the full action of antimony is depression of the circulation, both as to force and rapidity; but such depression is often preceded by a rise in the pulse-rate, and a similar rise may occur before death in the later stages of poisoning.

Ackermann, indeed, experimenting upon healthy men with emetic doses (about 3/4 gr. of the tartrate), found a prolonged rise in the pulse-rate, to an average maximum extent of 42 per minute, and this was distinctly related to the gastric symptoms. The rise began only with the onset of nausea, and increased with the occurrence of vomiting, after which the pulse fell to an ordinary level: it became also soft and weak in proportion to its quickness, but he did not observe any decided fall below the normal rate at any period (Abstract, British and Foreign Review, April, 1859).

These observations were carefully made, the pulse being examined every five minutes for several hours, but they illustrate only the effect of one or two doses. There can be little doubt that a longer course of the same, or a larger initial dose, would have induced the slowing of pulse which has been verified by so many observers; but we may note a parallel observation made by Trousseau, that in some few persons taking antimony the pulse became and continued quick, as well as weak and irregular. Usually, as at first stated, slowing of the pulse is a marked and somewhat persistent effect of antimony, and especially so when vomiting does not occur at all, or after it has ceased: from six to ten beats per minute is an average amount of decrease after doses of 1 to 2 gr., but it may vary from three beats to forty (Pecholier, Bonamy). Gubler has noted a proportion between the ultimate fall and the primary increase. (Whether such primary increase, when it occurs, is due to a temporary excitation of the whole system, or to paralysis of the regulating branches of the vagus, has been a question: the former is, I think, more probable). Arterial pressure is much diminished, and the curves of a sphygmogram may be almost effaced (Bordier): more or less venous congestion also occurs.

After very large doses, any acceleration is but slight and transient, before the blood-current becomes slow and almost imperceptible. In frogs, dogs, or rabbits, when a sufficient dose has been introduced by any channel, the cardiac contractions also soon become slower, weaker, and irregular, the auricles contracting oftener than the ventricles. When death occurs from the drug it is said to be always through cardiac palsy (Richardson), the general state of collapse being secondary to failure of the circulation. Arrest finally occurs in diastole, and the irritability of the cardiac muscle is found to be impaired or lost (Radziejewski, Bellini), probably owing to a directly paralyzing influence on the cardiac muscular structure when reached by the drug after absorption. When antimony is applied to the batrachian heart, removed from the body, similar slowing and arrest take place, which is another reason for considering the action to be directly on the muscular structure. It is curious that in animals subjected to toxic doses, death can be delayed for some hours by dividing the vagi (Majen-die).

Rabuteau notes the remarkable analogy between the above action of antimony, and that of digitalis. Nobiling traced the depressant effects described to the potash, rather than to the antimony in tartar emetic, but his observations have been disproved.