Vascular toxicity, cyanides

Ballantyne and Salem discuss the experimental and human clinical toxicology of cyanides with particular reference to their potential for apphcation as chemical warfare weapons and use by terrorists. They consider repeated exposure toxicity as well as specific organ, tissue, and functional end-point toxicity. Among the functional end-point toxicities, they review neurotoxicity, cardio-toxicity, vascular toxicity, developmental and reproductive toxicity, and genotoxicity. They conclude this review of the toxicology of cyanide by describing emergency first aid and poison-control... 

Vascular toxicity and influences of cyanide on vascular reflexes... 

Ibrahim et al. 1963). Aiken and Braitman (1989) determined that cyanide has a direct effect on neurons not mediated by its inhibition of metabolism. Consistent with the view that cyanide toxicity is due to the inability of tissue to utilize oxygen is a report that in cyanide-intoxicated rats, arterial p02 levels rose, while carbon dioxide levels fell (Brierley et al. 1976). The authors suggested that the low levels of carbon dioxide may have led to vasoconstriction and reduction in brain blood flow therefore, brain damage may have been due to both histotoxic and anoxic effects. Partial remyelination after cessation of exposure has been reported, but it is apparent that this process, unlike that in the peripheral nervous system, is slow and incomplete (Hirano et al. 1968). The topographic selectivity of cyanide-induced encephalopathy may be related to the depth of acute intoxication and distribution of blood flow, which may result in selected regions of vascular insufficiency (Levine 1969). 

Nitroprusside [nye troe PRUSS ide] is administered intravenously, and causes prompt vasodilation, with reflex tachycardia. It is capable of reducing blood pressure in all patients, regardless of the cause of hypertension. The drug has little effect outside the vascular system, acting equally on arterial and venous smooth muscle. [Note Because nitroprusside also acts on the veins, it can reduce cardiac preload.] Nitroprusside is metabolized rapidly (t1/2 of minutes) and requires continuous infusion to maintain its hypotensive action. Sodium nitroprusside exerts few adverse effects except for those of hypotension caused by overdose. Nitroprusside metabolism results in cyanide ion production, although cyanide toxicity is rare and can be effectively treated with an infusion of sodium thiosulfate to produce thiocyanate, which is less toxic and is eliminated by the kidneys (Figure 19.14). [Note Nitroprusside is poisonous if given orally because of its hydrolysis to cyanide.]... 

This reaction normally represents hepatic detoxification of cyanide ions produced from nitroprusside in erythrocytes. The SCN- is 99% less toxic than CN-. NaSCN was also still official in the NF X (1960) as an antihypertensive drug. A nitroprusside mechanism on vascular smooth muscle by interference with the role of Ca2+ in the muscle contraction process has also been suggested. 

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