Isopen-20 Mechanism of Action

Pharmacology: Pharmacodynamics: Isosorbide-5-mononitrate, an organic nitrate, forms free radical nitric oxide (NO). In smooth muscle, NO activates guanylate cyclase which increases guanosine 3' 5' monophosphate (cGMP) concentration leading to dephosphorylation of myosin light chains and smooth muscle relaxation. Produces a vasodilator effect on the peripheral veins and arteries with more prominent effects on the veins. Primarily reduces cardiac oxygen demand by decreasing preload; may modestly reduce afterload; dilates coronary arteries and improves collateral flow to ischemic regions.
Pharmacokinetics: Absorption: Isosorbide-5-mononitrate is rapidly absorbed from the GI tract with peak plasma concentration within 30 to 60 minutes. Because Isosorbide-5-mononitrate does not undergo first-pass hepatic metabolism, the bioavailability of Isosorbide-5-mononitrate conventional tablets is approximately 100%. The onset of action occurs within 20 minutes. Food delays the rate but not the extent of absorption (less than 10%).
Distribution: Isosorbide-5-mononitrate is distributed into blood cells, saliva and tissue with an apparent volume of distribution of approximately 0.6-0.7 L/kg in adults. The distribution half-life is 8.6 minutes. Isosorbide-5-mononitrate is approximately 4-5% bound to plasma protein.
Metabolism: Isosorbide-5-mononitrate is metabolized principally in the liver, but it does not undergo first-pass hepatic metabolism. Isosorbide-5-mononitrate undergoes denitration to form Isosorbide, glucuronidation to form 5-isosorbide mononitrate glucuronide and denitration/dehydration to form sorbitol. These metabolites apparently do not have pharmacologic activity.
Excretion: Isosorbide-5-mononitrate and metabolites are excreted mainly via urine (96% and 2% as unchanged drug) and in feces (1%) within 5 days (excretion about 93% occurs within 48 hours). Elimination half-life is approximately 5 hours. Renal clearance accounts only for about 4% of total body clearance. Isosorbide-5-mononitrate significantly removes from the blood during hemodialysis but not the peritoneal dialysis. The rate of clearance does not appear to be affected by age, cardiac disease, or renal or hepatic impairment.