MECHANISM OF ACTION 

  • Metabolised to nitric oxide that activates guanylyl cyclase, increasing production of cGMP in vascular tissues.
  • This secondary messenger causes smooth muscle relaxation resulting in coronary artery dilatation (increasing oxygen supply to myocardium) and systemic vasodilatation (reducing preload and thereby reducing oxygen demand).

INDICATIONS

  • Prophylaxis and treatment of angina
  • LVF

CAUTIONS AND CONTRA-INDICATIONS

  • Hypersensitivity to nitrates.
  • Hypotension/hypovolaemia .
  • Cardiac outflow obstruction (aortic stenosis, cardiac tamponade, hypertrophic obstructive cardiomyopathy, constrictive pericarditis).
  • Closed-angle glaucoma

SIDE-EFFECTS

  • Postural hypotension.
  • Headache.
  • Tachycardia.
  • Dizziness
  • METABOLISM AND HALF-LIFE
  • Metabolised by the liver and other cells including red blood cells.
  • t½ is variable – for intravenous GTN t½ is 4–6min and for oral ISMN t½ is 6h.

MONITORING 

  • BP monitoring is required for intravenous infusion.

DRUG INTERACTIONS

  • Reduce the anticoagulant effect of low molecular weight heparin.
  • Risk of severe hypotension with phosphodiesterase type 5 inhibitors (e.g. sildenafil)

IMPORTANT POINTS

  • Tolerance to nitrates may develop hence patients should have at least 8h nitrate-free every 24h (except when administered intravenously in the acute setting)