Treatment of Nitrate Drug in Ischemic Heart Disease (angina)

The organic nitrates are widely used in the management of coronary artery disease. They are given not only to patients with stable angina pectoris, but also to those with unstable angina, acute myocardial infarction, and heart failure. Although they are effective for the treatment of these disorders, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy. Long-acting nitrates can provide protection against the development of angina for up to 12 hours each day if an appropriate dosing regimen or formulation is used. Regimens with proved effectiveness include intermittent transdermal nitroglycerin, standard-formulation isosorbide mononitrate given eccentrically, and sustained-release isosorbide mononitrate given once daily, but there is some concern that nitrate-free periods may have adverse effects in some patients. Although the mechanism of nitrate tolerance has remained elusive, studies in animals suggest that nitrate therapy causes specific biochemical responses in the vasculature that limit the vasodilator effects of nitrates.