| Indication |
For the prevention of angina pectoris due to coronary artery
disease and the treatment of acute and chronic angina pectoris,
hypertension, and myocardial infarction. |
| Pharmacodynamics |
Isosorbide-5-mononitrate, the long-acting metabolite of
isosorbide dinitrate, is used as a vasodilatory agent in the management
of angina pectoris. By dilating the vessels, it lowers the blood
pressure and reduces the left ventricular preload and afterload,
therefore, leads to a reduction of myocardial oxygen requirement. |
| Mechanism of action |
Similar to other nitrites and organic nitrates, Isosorbide
Mononitrate 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 |
100% |
| Volume of distribution |
|
| Protein binding |
5% |
| Metabolism |
Hepatic |
| Route of elimination |
Isosorbide mononitrate is primarily metabolized by the liver, but
unlike oral isosorbide dinitrate, it is not subject to first-pass
metabolism.
Isosorbide mononitrate is cleared by denitration to isosorbide and
glucuronidation as the mononitrate, with 96% of the administered dose
excreted in the urine within 5 days and only about 1% eliminated in the
feces. At least six different compounds have been detected in urine,
with about 2% of the dose excreted as the unchanged drug and at least
five metabolites. |
| Half life |
5 hours |
| Clearance |
- 120–122 mL/min [Single dose of 60 mg PO]
- 151–187 mL/min [Single dose of extended-release tablet 60 mg PO]
- 132-151 mL/min [Multiple doses of extended release tablet 60 mg PO]
- 119-140 mL/min [Multiple doses of extended release tablet 120 mg PO]
|
| Toxicity |
Symptoms of overdose include vasodilatation, venous pooling,
reduced cardiac output, and hypotension. There are no data suggesting
what dose of isosorbide mononitrate is likely to be life-threatening in
humans. In rats and mice, there is significant lethality at doses of
2000 mg/kg and 3000 mg/kg, respectively. |
