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)