Intravenous glyceryl trinitrate (nitroglycerin). A review of its pharmacological properties and therapeutic efficacy

Abstract

The recently introduced preparation of intravenous glyceryl trinitrate (nitroglycerin) provides a rapid steady therapeutic blood concentration of nitrates during continuous infusion. Intravenous glyceryl trinitrate causes venodilation at low doses, but at higher doses dilates both arteries and veins. Its principal haemodynamic effects at therapeutic dosages include a decrease in blood pressure in preload (left ventricular filling pressure) and in determinants of afterload, and a decrease in myocardial oxygen demand. Human pharmacokinetic data are few and difficult to interpret due to wide interstudy and interindividual variation. There is no close correlation between infusion rate, blood concentration and haemodynamic effects. The nature of the patient population treated with intravenous glyceryl trinitrate has largely precluded the use of a placebo, but in open trials the drug has been used successfully in the treatment of unstable angina, left ventricular failure accompanying acute myocardial infarction and in the control of hypertension associated with cardiac surgery at dosages titrated to achieve a specific end-point. Favourable haemodynamic responses have been achieved in very short term studies in congestive heart failure, and preliminary studies suggest that institution of intravenous glyceryl trinitrate early after acute myocardial infarction may limit ischaemic damage. However, use of the drug in acute myocardial infarction remains controversial. Intravenous glyceryl trinitrate is generally well tolerated, although hypotension and headache occur occasionally, and sinus tachycardia and bradycardia less frequently. Careful titration of dosage is required (beginning at 5 micrograms/min), and if the infusion sets contain polyvinylchloride, the delivered dose is lower than that calculated, because of adsorption of glyceryl trinitrate onto the plastic tubing.