Sublingual or buccal nitroglycerin is used either to terminate an acute attack of angina or for short-term prevention of angina. Nitroglycerin is also the mainstay of therapy for relieving acute coronary vasospasm because of its rapid onset of action. When taken at the onset of chest pain, the effects of nitroglycerin appear within 2 to 5 minutes; however, the true duration of action is difficult to establish in patients with secondary angina, since the onset of pain causes patients to reduce their physical activity, and this alone can ameliorate the symptoms. Isosorbide dinitrate and pentaerythritol tetranitrate also can be taken sublingually, shortly before antici pated physical or emotional stress, to prevent anginal attacks.
Nitroglycerin ointment applied to the skin acts within 15 minutes and may produce its effects for 2 to 6 hours. Sustained-release transdermal nitroglycerin has been shown to deliver an antianginal effect for 2 to 4 hours following small doses and up to 24 hours after larger doses.
Orally administered long-acting nitrates, including nitroglycerin and various nitrate esters, nitroglycerin ointment, and transdermal nitroglycerin, were developed with the goal of providing a nitrate preparation that would have prolonged pharmacological activity for prophylactic therapy of angina pectoris. Considerable controversy surrounds the therapeutic use of the orally active agents because of their extensive first-pass metabolism, and many clinicians consider them to be ineffective. More recently, however, numerous clinical investigations have demonstrated the efficacy of transdermal nitroglycerin, although tolerance can be a problem with prolonged transdermal exposure to nitro-glycerin. The drugs and dosage forms of organic nitrates available for therapeutic use, their usual dose, onset of action, and duration of action are summarized in Table 17.2.
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