|
 | |
| Supplement |
|---|
| Name: | Nitroglycerin - Drug | | Description: | Nitroglycerin was the first medication used in 1879 by William Murrell for the treatment of angina pectoris [1] and still remains first-line drug therapy for many patients (show table 1) [2,3]. Its use, however, is complicated by the development of tolera |
|
Nitroglycerin was the first medication used in 1879 by William Murrell for the treatment of angina pectoris [1] and still remains first-line drug therapy for many patients (show table 1) [2,3]. Its use, however, is complicated by the development of tolerance with continuous therapy.
MECHANISM OF ACTION — Nitrates dilate veins, arteries, and coronary arteries by relaxing vascular smooth muscle [4]. They produce these effects by entering vascular smooth muscle cells where they are metabolized to 1,2-glyceryl dinitrate and nitrite, via mitochondrial aldehyde dehydrogenase (mtALDH), and then nitric oxide and S-nitrosothiols (show figure 1) [5]. Sulfhydryl groups on mtALDH are required for activity, which can explain the known sulfhydryl requirement for vascular smooth muscle relaxation by nitrates [5].
The nitrosothiols stimulate guanylate cyclase to produce cyclic guanosine monophosphate (cGMP), which causes smooth muscle relaxation by decreasing intracellular calcium levels [6]. Increased catabolism of cGMP attenuates the vascular effects of nitrate therapy [7]. (See "The coronary microcirculation: Physiology", section on Organic nitrates).
Most of the antiischemic efficacy of nitrates pertains to their ability to decrease myocardial oxygen demand as a result of systemic vasodilatation rather than any activity as a coronary vasodilator. Nitrates do not have a direct effect on cardiac chronotropy or inotropy.
Effect on systemic hemodynamics — The nitrates are primarily venodilators due to increased bioavailability to venous smooth muscle cells. Venodilation lowers preload (left ventricular end-diastolic pressure) and therefore reduces wall stress, resulting in a decrease in myocardial oxygen demand. The fall in preload is more pronounced with sitting or standing. |
| |
