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 nitrous 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 nitrous 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

Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.