Pharm 101: Nitroprusside

Class

Vasodilator antihypertensive

Pharmacodynamics

• Dilates both arterial and venous vessels, decreasing vascular resistance
• Action is a result of activation of guanylyl cyclase, by release of nitric oxide, which increases cGMP and causes smooth muscle relaxation

Pharmacokinetics

• Structure is a complex of iron, cyanide groups and a nitroso moiety
• Given IV, rapid onset of action
• Duration of action of 1-10 minutes
• Rapidly metabolised by uptake into red bloods cells with subsequent release of nitric oxide and cyanide
  • Cyanide is then metabolised to the less toxic thiocyanate, which is distributed in extracellular fluid and eliminated slowly by kidneys
• Metabolite is eliminated by the kidney

Clinical uses

• Given as intravenous infusion for rapid pressure reduction in arterial hypertension
• Dosage begins at 0.5 mcg/kg/min and may be increased up to 10 mcg/kg/min as necessary to control blood pressure
• Requires intra-arterial blood pressure monitoring

Adverse effects

• Excessive hypotension
• Higher rates of infusion, if continued for more than an hour, may result in toxicity
• Cyanide toxicity
  • Metabolic acidosis, arrhythmias and excessive hypotension
  • Sodium thiosulfate (sulfur donor facilitating metabolism) and hydroxycobalamin (combines with cyanide to form the nontoxic cyanocobalamin) can be used for prophylaxis or treatment of cyanide toxicity during nitroprusside infusion
• Thiocyanate (metabolite) toxicity
  • May accumulate over prolonged administration, days or more
  • Renal failure predisposes due to decreased elimination
  • Psychosis, seizures, weakness
• Delayed hypothyroidism due to thiocyanate inhibition of iodide uptake by thyroid
• Methaemoglobinaemia can occur during infusion

Further Reading

• Nickson C. Cyanide Poisoning
• Nickson C. Methaemoglobinaemia