indication

For the prevention of angina pectoris due to coronary artery disease.

pharmacology

Isosorbide Dinitrate is a moderate to long acting oral organic nitrate used for the relief and prophylactic management of angina pectoris. It relaxes the vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end- diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure.

mechanism of action

Similar to other nitrites and organic nitrates, isosorbide dinitrate is converted to nitric oxide (NO), an active intermediate compound which activates the enzyme guanylate cyclase (atrial natriuretic peptide receptor A). This stimulates the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP) which then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber. The subsequent release of calcium ions results in the relaxation of the smooth muscle cells and vasodilation.

toxicity

Symptoms of overdose include reduced cardiac output and hypotension.

biotransformation

Hepatic

absorption

Absorption of isosorbide dinitrate after oral dosing is nearly complete, but bioavailability is highly variable (10% to 90%), with extensive first-pass metabolism in the liver. The average bioavailability of isosorbide dinitrate is about 25%.

half life

1 hour

drug interactions

Dihydroergotamine: Possible antagonism of action

Dihydroergotoxine: Possible antagonism of action

Ergonovine: Possible antagonism of action

Ergotamine: Possible antagonism of action

Methylergonovine: Possible antagonism of action

Methysergide: Possible antagonism of action

Sildenafil: Possible significant hypotension with this combination

Tadalafil: The vasodilatory effects of Isosorbide dinitrate may be increased by Tadalafil. Severe hypotension may occur. Concomitant therapy is contraindicated.

Telithromycin: Telithromycin may reduce clearance of Isosorbide Dinitrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Isosorbide Dinitrate if Telithromycin is initiated, discontinued or dose changed.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Udenafil: The vasodilatory effects of Isosobide dinitrate may be increased by Udenafil. Severe hypotension may occur. Concomitant therapy is contraindicated.

Vardenafil: The vasodilatory effects of Isosorbide dinitrate may be increased by Vardenafil. Severe hypotension may occur. Concomitant therapy is contraindicated.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of isosorbide dinitrate by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of isosorbide dinitrate if voriconazole is initiated, discontinued or dose changed.