The gastrointestinal absorption of organic nitrates

It has been nearly 100 years since William Murrelli of England treated his first angina patient with nitroglycerin, and controversy appears to have originated from the extensive investigations of Needleman of the Washington University Medical School on the action of nitrates in animals.

Abstract

It has been nearly 100 years since William Murrelli of England treated his first angina1 patient with nitroglycerin. He directed the patient to drop 3 drops of a 1 percent solution of nitroglycerin into l/2 02 of water and take it three times daily. Murrel was impressed by the improvement in the patient’s condition and his ability to abort an attack by swallowing a dose of his medicine. There is no doubt that an adequate therapeutic quantity of the drug was absorbed. Until the advent of reserpine and other antihypertensive drugs, erythrityl tetranitrate (30 mg) and mannitol hexanitrate (15 mg) were used extensively in the treatment of hypertension.2 There appeared to be no question concerning the absorption of either of these drugs. The hypotensive maximal action occurred within 1.5 hours and persisted for 5 to 6 hours. Although these two hypotensive agents have been largely abandoned, they have been replaced by antianginal drugs of the nitrate class such as isosorbide dinitrate and pentaerythritol tetranitrate. In addition, nitroglycerin has become available in sustained release forms, and this development has precipitated the question of the absorption of nitroglycerin when administered in this form rather than as a sublingual tablet. This controversy appears to have originated from the extensive investigations of Needleman of the Washington University Medical School on the action of nitrates in animals. Needleman’s work, supported by the American Heart Association, was reported to the Wall Street Journal, and the resulting publicity has caused patients to lose confidence in these drugs. The thrust of Needleman’s thesis is summarized by him in a comment in the Annals of Internal Medicine.3 He states: “Orally administered organic nitrates are absorbed into the portal circulation and are rapidly and completely degraded by a liver enzyme before reaching the systemic circulation and therefore can have little chance of producing vasodilation.”