Sodium nitroprusside (and other nitrovasodilators) relax both arteriolar and venous smooth muscle. Its primary mechanism of action is shared with other nitrates (eg, hydralazine and nitroglycerin). As nitrovasodilators are metabolized, they release nitric oxide, which activates guanylyl cyclase. This enzyme is responsible for the synthesis of cyclic guanosine 3′,5′-monophosphate (cGMP), which controls the phosphorylation of several proteins, including some involved in the control of free intracellular calcium and smooth muscle contraction.
Nitric oxide, a naturally occurring potent vasodilator released by endothelial cells (endothelium-derived relaxing factor), plays an important role in regulating vascular tone throughout the body. Its ultrashort half-life (<5 s) provides nimble endogenous control of regional blood flow. Inhaled nitric oxide is a selective pulmonary vasodilator that is used in the treatment of reversible pulmonary hypertension.
Sodium nitroprusside is a potent and reliable antihypertensive. It is usually diluted to a concentration of 100 μg/mL and administered as a continuous intravenous infusion (0.25–5 μg/kg/min). Its rapid onset of action (1–2 min) and fleeting duration of action allow precise titration of arterial blood pressure. The potency of this drug requires frequent blood pressure measurements—or, preferably, intraarterial monitoring—and the use of mechanical infusion pumps.
Cyanide ions binding to tissue cytochrome oxidase (which interferes with normal oxygen utilization) underlies the development of acute cyanide toxicity. Acute cyanide toxicity, characterized by metabolic acidosis, cardiac arrhythmias, and increased venous oxygen content (as a result of the inability to utilize oxygen), may develop as a result of prolonged exposure to sodium nitroprusside. An early sign of cyanide toxicity is the acute resistance to the hypotensive effects of increasing doses of sodium nitroprusside (tachyphylaxis). Cyanide toxicity is more likely if the cumulative daily dose of sodium nitroprusside is greater than 500 μg/kg or if the drug is administered at infusion rates greater than 2 μg/kg/min for more than a few hours. The pharmacological treatment of cyanide toxicity depends on providing alternative binding sites for cyanide ions by administering sodium thiosulfate (150 mg/kg over 15 min) or 3% sodium nitrite (5 mg/kg over 5 min), which oxidizes hemoglobin to methemoglobin. Additionally, hydroxocobalamin combines with cyanide to form cyanocobalamin (vitamin B12) and likewise can be administered to treat cyanide poisoning. Methemoglobinemia from excessive doses of sodium nitroprusside or sodium nitrite can be treated with methylene blue (1–2 mg/kg of a 1% solution over 5 min), which reduces methemoglobin to hemoglobin.
The combined dilation of venous and arteriolar vascular beds by sodium nitroprusside results in reductions of preload and afterload. Arterial blood pressure falls due to the decrease in peripheral vascular resistance. In opposition to any favorable changes in myocardial oxygen requirements are reflex-mediated responses to the fall in arterial blood pressure. These include tachycardia ...