TRC: Nitrates

Nitrates

Nitrates have a quick and direct vasodilating effect. They affect venous vessels, and at higher doses also arterial vessels including the coronary arteries. Due to their vasodilating effect, the venous return to the heart decreases, which in turn reduces myocardial wall tension and thus oxygen demand. The oxygen supply is enhanced by dilating the coronary arteries. Nitrates are mostly prodrugs, which decompose to form NO and then activate the guanylate cyclase enzyme.

Nitrates can relieve symptoms of an angina attack or myocardial infarction within a few minutes. The drugs are also indicated for maintenance treatment of angina and (acute) heart failure.

Nitrates are sublingually (oromucosally) or transdermally administered in order to avoid the large first-pass effect in the liver, where nitrates are inactivated. A problem with continuous nitrate therapy is the development of tolerance tolerance in the arterial-arterioral responses. The favourable venous and pulmonary vascular effects do, however, persist with chronic therapy. A nitrate-free period of 8–12 hours per 24 hours can prevent tolerance. Nitroglycerin and isosorbide dinitrate are indicated to treat an attack of angina pectoris. Headache is the main adverse effect in the beginning of treatment. Other described symptoms are the result of acute vasodilation, resulting in symptoms of hypotension such as dizziness, fatigue, nausea, and palpitations.