"Nov. 19, 2012 -- Unemployment and a history of job loss may raise the risk for heart attack, a new study suggests.
The risk of heart attack may be highest during the first year of unemployment. And the more jobs a person loses, the hi"...
- Patient Information:
Details with Side Effects
Isosorbide mononitrate is the major active metabolite of isosorbide dinitrate (ISDN), and most of the clinical activity of the dinitrate is attributable to the mononitrate.
The principal pharmacological action of isosorbide mononitrate, due to its nitric oxide metabolite, is direct relaxation of vascular smooth muscle. The result is dilatation of peripheral arteries and veins, especially the latter. Dilation 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 (afterload). Dilatation of the coronary arteries also occurs. The relative importance of preload reduction, afterload reduction, and coronary dilatation remains undefined.
Dosing regimens for most chronically used drugs are designed to provide plasma concentrations that are continu-ously greater than a minimally effective concentration. This strategy is inappropriate for organic nitrates. Several well-controlled clinical trials have used exercise testing to assess the antianginal efficacy of continuously delivered nitrates. In the large majority of these trials, active agents were indistinguishable from placebo after 24 hours (or less) of continuous therapy. Attempts to overcome tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours has their antianginal efficacy been restored. The drug-free interval sufficient to avoid tolerance to isosorbide mononitrate has not been completely defined. In the only regimen of twice-daily isosorbide mononitrate that has been shown to avoid development of tolerance, the two doses of Ismo (isosorbide mononitrate) tablets are given 7 hours apart, so there is a gap of 17 hours between the second dose of each day and the first dose of the next day. Taking account of the relatively long half-life of isosorbide mononitrate this result is consistent with those obtained for other organic nitrates. The same twice-daily regimen of Ismo (isosorbide mononitrate) tablets successfully avoided significant rebound/withdrawal effects. The incidence and magnitude of such phenomena have appeared, in studies of other nitrates, to be highly dependent upon the schedule of nitrate administration.
In humans, isosorbide mononitrate is not subject to first pass metabolism in the liver. The absolute bioavailability of isosorbide mononitrate from Ismo (isosorbide mononitrate) tablets is nearly 100%. Maximum serum concentrations of isosorbide mononitrate are achieved 30 to 60 minutes after ingestion of Ismo. The volume of distribution of isosorbide mononitrate is approximately 0.6 L/kg, and less than 4% is bound to plasma proteins. It is cleared from the serum by denitration to isosorbide; glucuronidation to the mononitrate glucuronide; and denitration/hydration to sorbitol. None of these metabolites is vasoactive. Less than 1% of administered isosorbide mononitrate is eliminated in the urine. The overall elimination half-life of isosorbide mononitrate is about 5 hours; the rate of clearance is the same in healthy young adults , in patients with various degrees of renal, hepatic, or cardiac dysfunction, and in the elderly. In a single-dose study, the pharmacokinetics of isosorbide mononitrate were dose-proportional up to at least 60 mg.
Controlled trials of single doses of Ismo (isosorbide mononitrate) tablets have demonstrated that antianginal activity is present about 1 hour after dosing, with peak effect seen from 1 to 4 hours after dosing. In placebo-controlled trials lasting 2 to 3 weeks, Ismo (isosorbide mononitrate) tablets were administered twice daily, in asymmetric regimens (with interdosing intervals of 7 and 17 hours) designed to avoid tolerance. One trial tested doses of 10 mg and 20 mg; one trial tested doses of 20 mg, 40 mg, and 60 mg; and three trials tested only doses of 20 mg. In each trial, the subjects were persons with known chronic stable angina, and the primary measure of efficacy was exercise tolerance on a standardized treadmill test. After initial dosing and for at least 3 weeks, exercise tolerance in patients treated with Ismo (isosorbide mononitrate) 20 mg tablets was significantly greater than that seen in patients treated with placebo, although there was some attenuation of effect with time. Treatment with Ismo (isosorbide mononitrate) tablets was superior to placebo for at least 12 hours after the first dose (i.e., 5 hours after the second dose) of each day. Significant tolerance and rebound phenomena were not observed. The 10-mg dose was not unequivocally superior to placebo, while the effect of the 40-mg dose was similar to that of the 20-mg dose. The 60-mg dose appeared to be less effective, and it was associated with a rebound phenomenon (early-morning worsening).
Last reviewed on RxList: 4/13/2009
This monograph has been modified to include the generic and brand name in many instances.
Additional Ismo Information
Ismo - User Reviews
Ismo User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options.