lution of sublingual nitroglycerin difficult. increasing salivation with chewing gum or artificial saliva products may prove useful in aiding dissolution of sublingual nitroglycerin. oral administration of nitroglycerin markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. ergotamine is known to precipitate angina pectoris. therefore, patients receiving sublingual nitroglycerin should avoid ergotamine and related drugs or be monitored for symptoms of ergotism if this is not possible. administration of nitroglycerin is contraindicated in patients who are using pde-5 inhibitors (e.g., sildenafil citrate, tadalafil, vardenafil hydrochloride). these compounds have been shown to potentiate the hypotensive effects of organic nitrates. a decrease in therapeutic effect of sublingual nitroglycerin may result from use of long-acting nitrates.

lution of sublingual nitroglycerin difficult. increasing salivation with chewing gum or artificial saliva products may prove useful in aiding dissolution of sublingual nitroglycerin. oral administration of nitroglycerin markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. ergotamine is known to precipitate angina pectoris. therefore, patients receiving sublingual nitroglycerin should avoid ergotamine and related drugs or be monitored for symptoms of ergotism if this is not possible. administration of nitroglycerin is contraindicated in patients who are using pde-5 inhibitors (e.g., sildenafil citrate, tadalafil, vardenafil hydrochloride). these compounds have been shown to potentiate the hypotensive effects of organic nitrates. a decrease in therapeutic effect of sublingual nitroglycerin may result from use of long-acting nitrates.

illing 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. mechanism of action nitroglycerin forms free radical nitric oxide (no) which activates guanylate cyclase, resulting in an increase of guanosine 3'5' monophosphate (cyclic gmp) in smooth muscle and other tissues. these events lead to dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and result in vasodilatation. pharmacodynamics consistent with the symptomatic relief of angina, digital plethysmography indicates that onset of the vasodilatory effect occurs approximately 1 to 3 minutes after sublingual nitroglycerin administration and reaches a maximum by 5 minutes postdose. effects persist for at least 25 minutes following nitroglycerin sublingual tablets administration. pharmacokinetics and drug metabolism absorption nitroglycerin is rapidly absorbed following sublingual administration of nitroglycerin sublingual tablets. mean peak nitroglycerin plasma concentrations occur at a mean time of approximately 6 to 7 minutes postdose (table 1). maximum plasma nitroglycerin concentrations (c max ) and area under the plasma concentration-time curves (auc) increase dose-proportionally following 0.3 to 0.6 mg nitroglycerin sublingual tablets. the absolute bioavailability of nitroglycerin from nitroglycerin sublingual tablets is approximately 40% but tends to be variable due to factors influencing drug absorption, such as sublingual hydration and mucosal metabolism. table 1 parameter mean nitroglycerin ( sd ) values 2 × 0 . 3 mg nitroglycerin sublingual tablets 1 × 0 . 6 mg nitroglycerin sublingual tablets c m a x , ng/ml 2.3 (1.7) 2.1 (1.5) t m a x , min 6.4 (2.5) 7.2 (3.2) auc ( 0 – ∞ ) , min 14.9 (8.2) 14.9 (11.4) t ½ , min 2.8 (1.1) 2.6 (0.6) 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%, respectively, 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.

on should not be considered a reliable method for determining the potency of the tablets. headaches can sometimes accompany treatment with nitroglycerin. in patients who get these headaches, the headaches may be a marker of the activity of the drug. treatment with nitroglycerin may be associated with lightheadedness upon standing, especially just after rising from a recumbent or seated position. this effect may be more frequent in patients who have also consumed alcohol. nitroglycerin sublingual tablets should be kept in the original glass container and must be tightly capped after each use to prevent loss of tablet potency.