Sodium nitroprusside

Regarding the drug sodium nitroprusside (SNP), the following statements are correct

EXCEPT which one?

a) SNP ultimately causes vasodilation via increased concentration of intracellular

cyclic guanylate monophosphate (cGMP)

b) Dicobalt edetate has a place in the management of toxicity induced by SNP

c) Vitamin B12 deficiency may predispose to SNP toxicity

d) SNP causes increased right-to-left intrapulmonary shunt

e) Thiocyanate, produced during one pathway of SNP metabolism, is non-toxic

Answer: e

Explanation

Sodium nitroprusside is metabolised in the erythrocytes. Sodium nitroprusside and

oxyhaemoglobin react to produce methaemoglobin plus nitric oxide and five molecules

of cyanide ions. It is the nitric oxide that is responsible for the clinical effect of the

drug, and the cyanide ions and their metabolites that potentially cause toxicity. Nitric

oxide is usually produced in the vascular endothelial cells via the action of nitric oxide

synthetase (inducible or constitutive) on L-arginine, an amino acid. In vascular

smooth muscle cells, nitric oxide avidly binds and activates guanylyl cyclase, which

dephosphorylates guanylate triphosphate (GTP) to cyclic guanylate monophosphate

(cGMP). It is the cGMP that precipitates a number of intracellular events that result in

smooth-muscle relaxation and thus vasodilation. Some of the cyanide ions produced

combine with the evolved methaemoglobin to produce cyanomethaemoglobin, which

is non-toxic. Residual cyanide ions combine with vitamin B12 to form the non-toxic

cyanocobalamin; others are converted in the liver mitochondria by rhodanase to

thiocyanate via the addition of a sulphydryl moiety. Thiocyanate itself is toxic and

when these pathways of elimination are exhausted, cyanide ions accumulate further

contributing to the toxicity. If toxicity develops, SNP therapy should be discontinued

and the cyanide chelator dicobalt edetate administered. Depleted sulphydryl stores

may be supplemented via the infusion of sodium thiosulphate. Intrapulmonary shunt

may be worsened by SNP by causing pulmonary vasodilation thus disrupting

hypoxic pulmonary vasoconstriction.