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DESCRIPTION
Nitroglycerin tablets are stabilized sublingual compressed
tablets that contain 0.3 mg (1/200 grain), 0.4 mg (1/150 grain), or 0.6 mg
(1/100 grain) nitroglycerin; as well as lactose monohydrate, NF; glyceryl
monostearate, NF; pregelatinized starch, NF; calcium stearate, NF powder; and
silicon dioxide, colloidal, NF.
Nitroglycerin, an organic nitrate, is a vasodilating agent. The chemical name
for nitroglycerin is 1, 2, 3 propanetriol trinitrate and the chemical structure
is:
C3H5N309
Molecular weight: 227.09
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CLINICAL PHARMACOLOGY
The principal pharmacological action of nitroglycerin is
relaxation of vascular smooth muscle. Although venous effects predominate,
nitroglycerin produces, in a dose-related manner, dilation of both arterial and
venous beds. Dilation of postcapillary vessels, including large veins, promotes
peripheral pooling of blood, decreases venous return to the heart, and reduces
left ventricular end-diastolic pressure (preload). Nitroglycerin also produces
arteriolar relaxation, thereby reducing peripheral vascular resistance and
arterial pressure (afterload), and dilates large epicardial coronary arteries;
however, the extent to which this latter effect contributes to the relief of
exertional angina is unclear.
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, and
pulmonary and systemic vascular resistance are also reduced by nitroglycerin
therapy. Heart rate is usually slightly increased, presumably due to a
compensatory response to the fall in blood pressure. Cardiac index may be
increased, decreased, or unchanged. Myocardial oxygen consumption or demand (as
measured by the pressure-rate product, tension-time index, and stroke-work
index) is decreased and a more favorable supply-demand ratio can be achieved.
Patients with elevated left ventricular filling pressures and increased systemic
vascular resistance in association with a depressed cardiac index are likely to
experience an improvement in cardiac index. In contrast, when filling pressures
and cardiac index are normal, cardiac index may be slightly reduced following
nitroglycerin administration.
Table 1
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Mean Nitroglycerin
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(SD) Values
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2 x 0.3 mg
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1 x 0.6 mg
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Parameter
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Nitroglycerin Tablets
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Nitroglycerin Tablets
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Cmax, ng/mL
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2.3 (1.7)
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2.1 (1.5)
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tmax, min
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6.4 (2.5)
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7.2 (3.2)
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| AUC(0–∞), min |
14.9 (8.2)
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14.9 (11.4)
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t1/2, min
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2.8 (1.1)
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2.6 (0.6)
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Distribution
The volume of distribution (VArea) of
nitroglycerin following intravenous administration is 3.3 L/kg. At plasma
concentrations between 50 and 500 ng/mL, the binding of nitroglycerin to plasma
proteins is approximately 60%, while that of 1,2- and 1,3-dinitroglycerin is 60%
and 30%, respectively.
Metabolism
A liver reductase enzyme is of primary importance in the
metabolism of nitroglycerin to glycerol di- and mononitrate metabolites and
ultimately to glycerol and organic nitrate. Known sites of extrahepatic
metabolism include red blood cells and vascular walls. In addition to
nitroglycerin, 2 major metabolites 1,2- and 1,3-dinitroglycerin, are found in
plasma. Mean peak 1,2- and 1,3-dinitroglycerin plasma concentrations occur at
approximately 15 minutes postdose. The elimination half-life of 1,2- and
1,3-dinitroglycerin is 36 and 32 minutes, respectively. The 1,2- and 1,3
dinitroglycerin metabolites have been reported to possess approximately 2% and
10% of the pharmacological activity of nitroglycerin. Higher plasma
concentrations of the dinitro metabolites, along with their nearly 10-fold
longer elimination half-lives, may contribute significantly to the duration of
pharmacologic effect. Glycerol mononitrate metabolites of nitroglycerin are
biologically inactive.
Elimination
Nitroglycerin plasma concentrations decrease rapidly with a mean
elimination half-life of 2 to 3 minutes. Half-life values range from 1.5 to 7.5
minutes. Clearance (13.6 L/min) greatly exceeds hepatic blood flow. Metabolism
is the primary route of drug elimination.
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