Bismuth compounds side effects

Bismuth arsphenamine sulphonate (Bismarsen , Fig. 9) a yellow powder readily soluble in water, was first prepared by Raiziss in 1924 [70]. Stokes and Chambers [71] were the first to use the drug clinically, giving two injections a week for 14 weeks. Four such courses separated by intervals of a fortnight were administered in all. Nevertheless the effects were slow compared with the arsphenamines, although the tonic effect was greater and the side effects less numerous. Relapses, particularly in the central nervous system (CNS) were more frequent. Consequently, Rayburn and Boyd emphasized the fact that some individuals with neurosyphilis who were intolerant to arsenic in any other form could nevertheless tolerate it in the form of Bismarsen [72]. The low toxicity, the tonic effect, and the ease of administration were the chief advantages in favor of Bismarsen . The other compounds of bismuth with arsenic were not extensively tested in humans. 

A striking feature of the cellular effects of bismuth compounds in animals (and one shared only by lead) is the production of intranuclear inclusion bodies of up to 5 ixm in diameter (87), for example, in the tubular epithelial cells of the kidney. Electron probe microanalysis shows that these contain both Bi and S, and so could be a complex with a Cys-rich protein such as metallothionein. Bismuth is known to be a potent inducer of renal metallothionein synthesis, and pretreatment of animals with bismuth salts can prevent some of the toxic side effects induced by cisplatin (88). The role of metallothionein in the pharmacology of bismuth remains to be established, but the strong involvement of zinc, also an inducer of metallothionein synthesis, in the metabolism of skin cells, for example, may be related. Like several other elements of Group V, the development of the biological chemistiy of Bi is hampered by the lack of good physical properties, in particular of a well-behaved NMR isotope. 

Toxicity in industry does not exist [3,4]. All lethal intoxications are attributed to therapeutic uses of bismuth compounds, mostly injections or long-lasting treatments. Reports in the 1970s from Australia and France about serious intoxications induced by bismuth led to an important reduction of its medical use. In the 1980s some bismuth compounds were successfully tested in the treatment of chronic gastritis without the former side effects. Nevertheless single cases of poisonings were also reported in the last years [35-37]. It appears that bismuth is not an essential element [4,7]. 

The ubiquitous distribution of both MTs and stress proteins may be exploited in cancer therapy regimens. MT may serve as an adjunct in cancer chemotherapy (Imura et al. 1991 Cherian et al. 1994). The selective induction of MT by bismuth in noncancer cells protects these cells from harmful side effects of a number of chemotherapeutics, including alkylating agents, antimetabolites, and mitotic inhibitors, but does not interfere with the efficacy of these compounds. Conversely, the presence of MT in tumors may act as a multidrug resistance factor in cancer chemotherapy (Cherian et al. 1994). While the role of stress proteins is not clearly defined, hyperthermia potentiates the antitumor effects of chemotherapeutics and radiotherapy (Nover 1991). 

The redistribution reaction in lead compounds is straightforward and there are no appreciable side reactions. It is normally carried out commercially in the liquid phase at substantially room temperature. However, a catalyst is required to effect the reaction with lead compounds. A number of catalysts have been patented, but the exact procedure as practiced commercially has never been revealed. Among the effective catalysts are activated alumina and other activated metal oxides, triethyllead chloride, triethyllead iodide, phosphorus trichloride, arsenic trichloride, bismuth trichloride, iron(III)chloride, zirconium(IV)-chloride, tin(IV)chloride, zinc chloride, zinc fluoride, mercury(II)chloride, boron trifluoride, aluminum chloride, aluminum bromide, dimethyl-aluminum chloride, and platinum(IV)chloride 43,70-72,79,80,97,117, 131,31s) A separate catalyst compound is not required for the exchange between R.jPb and R3PbX compounds however, this type of uncatalyzed exchange is rather slow. Again, the products are practically a random mixture. 

---