Activity and Toxicity of Nitroprusside

The primary action of sodium nitroprusside is smooth-muscle relaxation, and intravenous administration produces a very rapid but easily reversible hypotension. Thus, the blood pressure can be regulated by altering infusion rate. Upon cessation of infusion the blood pressure returns very quickly to its original value, implying a rapid breakdown of the complex. The complex is 30—1000 times more potent than simple nitrites [36], with which it is most often compared. Nitroprusside is light sensitive [37] and needs to be used quickly after dilution. 

There is no known contraindication, and an upper limit of 3 mg/kg for the total dose is recommended [38]. The major source of toxicity comes from the rapid breakdown and release of cyanide ion. Studies in vitro show that this occurs when nitroprusside is incubated with plasma, serum, hemoglobin and whole blood [34]. There is evidence that the principal 

The released CN is transformed into SCN by a hepatic and renal enzyme, rhodanese [43—45], this sulfuryl transferase being discovered in 1933 [46]. The enzymatic reaction proceeds slowly unless sulfur is supplied and is stimulated by thiosulfate, which is therefore a powerful antidote for CN poisoning. Another antidote is vitamin B12, and results indicate that as plasma cyanide increases the vitamin Bj2 level decreases suggesting that the vitamin may be a cofactor of rhodanese. Vitamin Bj2 will be in the aqua (not hydroxo) form at physiological pH [47], and cyanocobalamin formation is believed to be responsible for the antidotal properties [48—50]. Side effects have also been noted, however, in this connection [43, 51], and low plasma B12 levels may complicate treatment. The direct interaction between nitroprusside and vitamin B12 has been examined by NMR and 1 1 and 1 2 adducts have been observed [47], 

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