Nitroglycerin relaxes vascular smooth muscle, with venous dilation predominating over arterial dilation. Its mechanism of action is presumably similar to that of sodium nitroprusside: metabolism to nitric oxide, which activates guanylyl cyclase, leading to increased cGMP, decreased intracellular calcium, and vascular smooth muscle relaxation.
Nitroglycerin relieves myocardial ischemia, hyper-tension, and ventricular failure. Like sodium nitro-prusside, nitroglycerin is commonly diluted to a concentration of 100 mcg/mL and administered as a continuous intravenous infusion (0.5–10 mcg/kg/ min). Glass containers and special intravenous tub-ing are recommended because of the adsorption of nitroglycerin to polyvinylchloride. Nitroglycerin can also be administered by a sublingual (peak effect in 4 min) or transdermal (sustained release for 24 route. Some patients seem to require higher than expected doses of nitroglycerin to achieve a given drop in blood pressure, particularly after chronic administration (tolerance). Tolerance may be due to depletion of reactants necessary for nitric oxide formation, compensatory secretion of vasoconstric-tive substances, or volume expansion. Dosing regi-mens that provide for intermittent periods of low or no drug exposure may minimize the development of tolerance.
Nitroglycerin undergoes rapid reductive hydro-lysis in the liver and blood by glutathione-organic nitrate reductase. One metabolic product is nitrite, which can convert hemoglobin to methemoglobin. Significant methemoglobinemia is rare and can be treated with intravenous methylene blue (1–2 mg/kg over 5 min).
Nitroglycerin reduces myocardial oxygen demand and increases myocardial oxygen supply by several mechanisms:
· The pooling of blood in the large-capacitance vessels reduces venous return and preload. The accompanying decrease in ventricular end-diastolic pressure reduces myocardial oxygen demand and increases endocardial perfusion.
· Any afterload reduction from arteriolar dilation will decrease both end-systolic pressure and oxygen demand. Of course, a fall in diastolic pressure may lower coronary perfusion pressure and actually decrease myocardial oxygen supply.
· Nitroglycerin redistributes coronary blood flow to ischemic areas of the subendocardium.Coronary artery spasm may be relieved.
The beneficial effect of nitroglycerin in patients with coronary artery disease contrasts with the coronary steal phenomenon seen with sodium nitroprusside. Preload reduction makes nitro-glycerin an excellent drug for the relief of cardiogenic pulmonary edema. Heart rate is unchanged or minimally increased. Rebound hypertension is less likely after discontinuation of nitroglycerin than following discontinuation of sodium nitroprusside. The prophylactic administration of low-dose nitro-glycerin (0.5–2.0 mcg/kg/min) during anesthesia of patients at high risk for perioperative myocardial ischemia remains controversial.
The effects of nitroglycerin on cerebral blood flow and intracranial pressure are similar to those of sodium nitroprusside. Headache from dila-tion of cerebral vessels is a common side effect of nitroglycerin.In addition to the dilating effects on the pulmonary vasculature (previously described for sodium nitroprusside), nitroglycerin relaxes bron-chial smooth muscle.
Nitroglycerin (50–100 mcg boluses) has been demonstrated to be an effective (but transient) uterine relaxant that can be beneficial during certain obstet-rical procedures if the placenta is still present in the uterus (eg, retained placenta, uterine inversion, uter-ine tetany, breech extraction, and external version of the second twin). Nitroglycerin therapy has been shown to diminish platelet aggregation, an effect enhanced by administration of N-acetylcysteine.
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