Bismuth, taken in a pulverulent form, exerts upon the gastric mucous membrane a sedative, slightly astringent effect, similar to that already described as its external action. Taken in a liquid (more soluble) form, the effects are still of the same kind, but produced by smaller doses and with more tendency to irritation. Whether pure bismuth salts, when taken internally, can exert an irritant poisonous action, or are in the largest doses practically innocuous, has been much disputed. Orfila and Meyer, in experiments on animals, found that both the nitrate and the subnitrate, in doses of 1 to 2 dr., caused vomiting, tremor, depression, and death, with postmortem evidence of gastro-enteritis ("Toxicologic," ii., p. 10; and Wib-mer: "Wirkungen," etc., i., p. 423). Kerner also records a case of a man who took 40 gr. of the subnitrate, and suffered from gastric oppression, and burning pain, bitter taste, thirst, loss of appetite, eructation, griping, bilious vomiting and relaxation, with vertigo, dimness of sight, and headache - the pulse was small and tense; and another case - a man who swallowed 2 dr. (mixed with cream of tartar), and died after violent symptoms of irritant poisoning, such as burning pain in the throat, purging, vomiting, cramps, suppression of urine, tremor, and paralysis: after death, inflammation and even gangrene were found in the course of the alimentary tract (Wibmer, loc. cit.). Sobernheim subjoins to these cases, one that after a 2-dr. dose proved fatal in nine days, with similar symptoms, including also delirium and general swelling of the face, limbs, and abdomen: in this instance also, inflammation and gangrene of the stomach and intestines were found ("Arzneimittellehre," 6th Ed., p. 265). Trousseau alludes to a similar case recorded by Pott in 1739, and Dr. Traill reports one where vomiting and pain followed the taking of 6 dr. (in divided doses). Christison describes "bismuth, in its saline combinations, as an active poison," and Taylor quotes some of the above cases as "proving that a substance very slightly soluble in water may exert a powerfully poisonous action on the human system."

On the other hand we must place the strong evidence of Trousseau and Monneret, and the daily experience of a majority of practitioners.

Trousseau states that during a very extensive use of the well-prepared subnitrate in doses of from 15 to 60 gr., he has never seen the slightest accident, or the least cause for apprehension ("Materia Medica," i.), while Monneret prescribed the enormous doses of 150 up to 900 gr. per diem, without any inconvenience resulting. He noted only slight constipation with lessened odor and blackened color of the faeces; there was no thirst, nausea, or pain, nor any evidence of inflammation, and the appetite was rather increased than diminished. Such doses as the above are not likely to be now prescribed, but many physicians order 10, 20, or 30 gr. several times daily without any evil result.

Trousseau and others explain the toxic symptoms above noted by the presence of arsenic as an impurity, and in some cases correctly, as shown by Taylor. H. C. Wood also records a case of bloody purging from the use of an adulterated drug, and the effects are certainly those of an irritant poison. Still, as a rule, there is no evidence of the requisite amount of arsenic for serious results, even in the most adulterated specimens of bismuth. Stille speaks of one-sixth of 1 per cent. as the maximum proportion found, while Parral and Garnier ascertained that preparations containing 0.129 per cent. did not poison dogs, even in doses of 200 to 500 gr. (see also Adulteration).

Monneret suggested that in the above cases, either a previous illness became suddenly exaggerated, or an excess of soluble nitrate acted as an irritant: the last alternative seems possible after recent evidence that soluble compounds of bismuth have an activity hitherto not supposed in pure preparations. The acetate (according to Bricka), the double tartrate (Rabuteau), and the ammonio-citrate (Stephanowitsch) given in large doses, produce poisonous symptoms very like those of the allied metals, gold and quicksilver. Rabuteau "at first held the classical opinion as to the remarkable harmlessness of bismuth," but his observations with the double tartrate, or "emetic" of bismuth and potash (C4H1K (BiO)O6) have convinced him that slight solubility explains the general absence of dynamic effects after large doses of the ordinary preparations. The tartrate is soluble in water without decomposition, and gives a metallic taste like that of ordinary "tartar emetic," it causes vomiting, and 30 to 60 gr. prove fatal to small dogs. In connection with this observation, it is noteworthy that in Kerner's fatal case, the patient took cream of tartar with his dose of bismuth, and the salt referred to by Rabuteau would probably be formed. Stephanowitsch records of the ammonio-citrate that its hypodermic injection, in the proportion of 1 gramme to each 1,000 grammes of body-weight, will kill animals, and that salivation and buccal abscess follow its use, as well as steatosis of liver, kidneys, and heart. The liver glycogen disappears under its prolonged administration (Lebedeff).

Although, therefore, some of the older cases were connected with the presence of arsenic, yet bismuth cannot be held entirely innocuous, and its activity clearly depends upon its solubility. The oxide, the subcar-bonate, and subnitrate, though but slightly soluble, may be taken up to some extent, especially when small doses are used. Thus, Odier, of Geneva, gave only a few grains, or less than a grain, and noticed occasionally vomiting, diarrhoea, a sense of heat, vertigo, and drowsiness. M. Guersant has noted colic and "sense of anxiety," and Rabuteau some general sedation, like the effect of antimony, and I have observed some clinical evidence in the same direction; but the existence of a chronic form of bismuth poisoning, marked by anaemia, swelling of gums, hemorrhage, etc., as described by Lussanna in man,1 and by Stephanowitsch in animals, has not been further verified. The only observation bearing upon it that I have found is one by Dr. Brinton, who states that if the subnitrate be taken continuously it will cause a bluish-red line on the gums, "similar to, but wider and more red than that known to be caused by lead" ("Diseases of Stomach," first edition, p. 197). I have not found this noted by any other observer, but lead has been suggested as an adulterant in the preparations used by Lussanna.

The action of Liquor Bismuthi differs somewhat from that of the solid compounds, and probably represents rather the real activity of the drug, independently of the mechanical effect of a powder; it is more irritant (H. Wood), and it has failed to relieve gastric pain when the subnitrate has succeeded (Macnamara). The carbonate is said to be less liable to irritate than the subnitrate, and yet to be more soluble in the gastric juice (Hannon); it does not perhaps absorb intestinal gases so readily as the subnitrate or oxide, but has better antacid powers, and is not so likely to constipate. The observer named, traced to it also some primary sedative effects, like those described by Rabuteau of the nitrate, viz., weakening and slowing of pulse, lessened appetite, and increased excretion of urine, but found that its continued use improved strength and vigor like iron preparations.

Synergists

Mechanical absorbents and antacids and sedatives. Magnesia is specially suited for combination with bismuth salts.

1 Dr. Lussanna remarks that Monneret's results with large doses "have destroyed the Orfilian scarecrow," but his own conclusions are almost as alarming as those of Orfila. From large doses, used apparently chiefly in tuberculous diarrhoea, he witnessed no irritation, nor any arrest of the malady, but supervention of a "colliquative and scorbutic state," connected, he presumes, with a solvent action on globulin - he traces a profuse epistaxis in a case of mesenteric tuberculosis to the use of bismuth, but gives no sufficient details of the cases on which his exceptional conclusions are based.

Incompatibles

Acids are said to be incompatible with the subnitrate of bismuth (Gubler), and some have advised the omission of all acids from the diet during its administration. Practically, however, their effect is only to favor the production of the more soluble nitrate, which should, in suitable dose, act favorably without discomfort, and a few minims of nitric acid are not infrequently prescribed with it; they should be omitted, however, if a merely protective effect is desired from an insoluble preparation. Bismuth prescribed with a strong solution of iodide of potassium precipitates as a red iodide, which is insoluble and apparently inactive (British Medical Journal, ii., 1870).

Therapeutical Action (External)