| Indication |
For the prevention of angina pectoris due to coronary artery disease. |
| Pharmacodynamics |
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. |
| 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%. |
| Volume of distribution |
|
| Protein binding |
Very low |
| Metabolism |
Hepatic |
| Route of elimination |
Not Available |
| Half life |
1 hour |
| Clearance |
Not Available |
| Toxicity |
Symptoms of overdose include reduced cardiac output and hypotension. |
