indication

For immediate reduction of blood pressure of patients in hypertensive crises, reduce bleeding during surgery, and for the treatment of acute congestive heart failure

pharmacology

Nitroprusside a powerful vasodilator relaxes the vascular smooth muscle and produce consequent dilatation of peripheral arteries and veins. Other smooth muscle (e.g., uterus, duodenum) is not affected. Sodium nitroprusside is more active on veins than on arteries.

mechanism of action

One molecule of sodium nitroprusside is metabolized by combination with hemoglobin to produce one molecule of cyanmethemoglobin and four CN- ions; methemoglobin, obtained from hemoglobin, can sequester cyanide as cyanmethemoglobin; thiosulfate reacts with cyanide to produce thiocyanate; thiocyanate is eliminated in the urine; cyanide not otherwise removed binds to cytochromes. Cyanide ion is normally found in serum; it is derived from dietary substrates and from tobacco smoke. Cyanide binds avidly (but reversibly) to ferric ion (Fe+++), most body stores of which are found in erythrocyte methemoglobin (metHgb) and in mitochondrial cytochromes. When CN is infused or generated within the bloodstream, essentially all of it is bound to methemoglobin until intraerythrocytic methemoglobin has been saturated. Once activated to NO, it activates guanylate cyclase in vascular smooth muscle and increases intracellular production of cGMP. cGMP stimulates calcium movement from the cytoplasm to the endoplasmic reticulum and reduces calcium available to bind with calmodulin. This eventually leads to vascular smooth muscle relaxation and vessel dilatation.

toxicity

Overdosage of nitroprusside can be manifested as excessive hypotension or cyanide toxicity or as thiocyanate toxicity. The acute intravenous mean lethal doses (LD₅₀) of nitroprusside in rabbits, dogs, mice, and rats are 2.8, 5.0, 8.4, and 11.2 mg/kg, respectively.

biotransformation

Metabolized by reaction with hemoglobin to produce cyanmethemoglobin and cynide ions

half life

Approximately 2 minutes

route of elimination

One molecule of sodium nitroprusside is metabolized by combination with hemoglobin to produce one molecule of cyanmethemoglobin and four CN¯ ions, thiosulfate reacts with cyanide to produce thiocyanate, thiocyanate is eliminated in the urine.