Glyceryl Trinitrate is a nitrovasodilator used in the management of angina pectoris, heart failure, and myocardial infraction.

Glyceryl Trinitrate exerts it vasodilator effect through nitric oxide which stimulates guanylate cyclase in the vascular smooth muscle cells and results in an increase in cyclic guanosine monophosphate. This monophosphate induces relaxation by lowering the free calcium concentration in the cytosol.

Venous dilation can decrease venous return as a result of venous pooling and lowers left ventricular diastolic volume and pressure.

Dilataion of arterioles can reduces both peripheral vascular resistance and left ventricular pressure at systole. The consequent effect is a reduction in the primary determinants of myocardial oxygen demand.

Glyceryl Trinitrate also has a coronary vasodilator effect which improves regional coronary blood flow to ischaemic areas resulting in improved oxygen supply to the myocardium.

 

Glyceryl Trinitrate also undergoes hydrolysis in plasma and are metabolized to glyceryl 1,2- and 1,3- dinitrates in liver which have less vasodilator activities than trinitrate. Because of the extensive first pass metabolism in the liver, the bioavailability is very low following oral administration.

Glyceryl 1,2- dinitrate	Glyceryl 1,3- dinitrate

Adverse effect:

Glyceryl Trinitrate may cause flushing of the face, dizziness, tachycardia, and throbbing headache. Large doses cause vomiting, restlessness, blurred vision, hyoitension, syncope and rarely cyanosis, and methaemoglobinaemia; impairment of respiration and bradycardia may ensue.Using topical Glyceryl Trinitrate preperation may has contact dermatitis. Sublungual or buccal Glyceryl Trinitrate tables usually produce localised burining sensation.

Glyceryl Trinitrate can lose its antiginal, anti-ischaemic effects and tolerance tends to develop in patients on continuous therapy. In addition, higher nitrate doses appear to induce attenuation in response. It is because repeated doses of a nitrate exhaust tissue stores of sulfhydryl group which use to convert organic nitrates to active form for stimulation guanylate cyclase. Development of tolerance can be avoided by providing a nitrate free interval. For trandermal Glyceryl Trinitrate preparation, the patch can be removed at night. For buccal, oral, and onintment preparations, the dose given at the end of the day can be omitted.