"Mutations in the TTN gene, which are commonly found in idiopathic dilated cardiomyopathy, also seem common in peripartum cardiomyopathyâ€”which may finally help explain why the latter condition occurs, new research suggests.
The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle, producing a vasodilator effect on both peripheral arteries and veins with more prominent effects on the latter. Dilation of the post-capillary vessels, including large veins, promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure (pre-load). Arteriolar relaxation reduces systemic vascular resistance and arterial pressure (after-load).
The mechanism by which nitroglycerin relieves angina pectoris is not fully understood. Myocardial oxygen consumption or demand (as measured by the pressure-rate product, tension-time index, and stroke-work index) is decreased by both the arterial and venous effects of nitroglycerin and presumably, a more favorable supply-demand ratio is achieved.
Nitroglycerin is rapidly metabolized in vivo, with a liver reductase enzyme having primary importance in the formation of glycerol nitrate metabolites and inorganic nitrate. Two active major metabolites, 1,2- and 1,3-dinitroglycerols, the products of hydrolysis, although less potent as vasodilators, have longer plasma half-lives than the parent compound. The dinitrates are further metabolized to mononitrates (considered biologically inactive with respect to cardiovascular effects) and ultimately glycerol and carbon dioxide.
Therapeutic doses of nitroglycerin may reduce systolic, diastolic and mean arterial blood pressure. Effective coronary perfusion pressure is usually maintained, but can be compromised if blood pressure falls excessively or increased heart rate decreases diastolic filling time.
Elevated central venous and pulmonary capillary wedge pressures, pulmonary vascular resistance and systemic vascular resistance are also reduced by nitroglycerin therapy. Heart rate is usually slightly increased, presumably a reflex response to the fall in blood pressure. Cardiac index may be increased, decreased, or unchanged. Patients with elevated left ventricular filling pressure and systemic vascular resistance values in conjunction with a depressed cardiac index are likely to experience an improvement in cardiac index. On the other hand, when filling pressures and cardiac index are normal, cardiac index may be slightly reduced.
In a pharmacokinetic study when a single 0.8 mg dose of Nitrolingual® Pumpspray (nitroglycerin lingual spray) was administered to healthy volunteers (n = 24), the mean Cmax and tmax were 1,041pg/mL • min and 7.5 minutes, respectively. Additionally, in these subjects the mean area-under-fhe-curve (AUC) was 12,769 pg/mL • min.
In a randomized, double-blind single-dose, 5-period cross-over study in 51 patients with exertional angina pectoris significant dose-related increases in exercise tolerance, time to onset of angina and ST-segment depression were seen following doses of 0.2, 0.4, 0.8 and 1.6 mg of nitroglycerin delivered by metered pumpspray as compared to placebo.
Additionally the drug was well tolerated as evidenced by a profile of generally mild to moderate adverse events.
Last reviewed on RxList: 11/3/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Nitrolingual Pumpspray Information
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