The symptoms of overdose from isosorbide mononitrate is associated with vasodilatation, venous pooling, reduced cardiac output, and hypotension. The oral LD 50 is 2010 mg/kg in rats and 1771 mg/kg in mice. Single doses less than 20 mg have not been adequately studied, while single doses greater than 20 mg have demonstrated no greater efficacy than doses of 20 mg. In clinical trials, Monit 20 tablets have been administered in a variety of regimens. The duration (if any) of antianginal activity beyond 12 hours has not been studied large controlled studies with other nitrates suggest that no dosing regimen should be expected to provide more than about 12 hours of continuous antianginal efficacy per day. This regimen has been shown to have antianginal efficacy beginning 1 hour after the first dose and lasting at least 5 hours after the second dose. Well-controlled studies have shown that tolerance to Monit 20 tablets is avoided when using the twice-daily regimen in which the two doses are given 7 hours apart. The dosing regimen for Monit 20 tablets provides a daily nitrate-free interval to avoid the development of this tolerance. Multiple studies of organic nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance.
Dosage adjustments are not necessary for elderly patients or patients with altered renal or hepatic function. For most patients, this can be accomplished by taking the first dose on awakening and the second dose 7 hours later. The recommended regimen of Monit 20 tablets is 20 mg (one tablet) twice daily, with the two doses given 7 hours apart. The duration of anti-anginal action of at least 12 hours was observed with an asymmetrical dosing regimen. The anti-anginal activity of isosorbide mononitrate was observed about 1 hour after dosing, and the peak effect was achieved from 1-4 hours after dosing. Organic nitrates can also relax other types of smooth muscles, including esophageal and biliary smooth muscle. Nitric oxide can also increase the rate of relaxation of cardiac muscles, which is an effect outside of vascular smooth muscles. The end effect of isosorbide mononitrate include decreased cardiac oxygen consumption, redistribution coronary flow toward ischemic areas via collaterals, and the relief of coronary spasms. Reduced cardiac preload and afterload caused by nitric oxide causes a reduction in myocardial oxygen consumption decreased myocardial oxygen demand, along with increased coronary blood flow, leads to an increased in the oxygen content of coronary sinus blood and the relief from ischemia. This leads to increased coronary blood flow. At larger doses, nitric oxide causes the resistance arteries and arterioles to dilate, reducing arterial pressure via coronary vasodilatation. The direct dilator effect on coronary arteries opposes the coronary artery spasm in variant angina or angina pectoris. Arterial relaxation leads to reduced systemic vascular resistance and systolic blood (aortic) pressure, decreasing to decreased cardiac afterload.
In healthy subjects, the stroke volume is decreased and venous pooling can occur in the standing posture, leading to postural hypotension and dizziness.Īt therapeutic doses of isosorbide mononitrate, nitric oxide has a bigger effect on larger muscular arteries over small resistance arteries. Nitric oxide works on both arteries and veins, but predominantly veins: by relaxing veins and reducing the central venous pressure, nitric oxide causes venous pooling and a decrease in the venous return to the heart, thus decreasing cardiac preload. The pharmacological action is mediated by the active metabolite, nitric oxide, which is released when isosorbide mononitrate is metabolized. Isosorbide mononitrate is an anti-anginal agent and vasodilator that relaxes vascular smooth muscle to prevent and manage angina pectoris. It decreases left ventricular pressure (preload) and arterial resistance (afterload). Isosorbide mononitrate relaxes vascular smooth muscles by stimulating cyclic-GMP. It causes reduction of preload and afterload and redistributes coronary flow to ischemic regions. It is a vasodilator with effects on both arteries and vein and also coronary vessels. Isosorbide-5-mononitrate is an active metabolite of isosorbide dinitrate.
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