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
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:
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.
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.
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.