NITRATE TOLERANCE IN ANGINA THERAPY - HOW TO AVOID IT

Tolerance is the attenuation or loss, of one or several of the effects of organic nitrates after long term administration. All organic nitra te regimens using frequent doses of long-acting nitrates (3 or more ti mes daily), continuous delivery systems [transdermal nitroglycerin (gl yceryl trinitrate) patches or continuous intravenous infusions of nitr oglycerin] or long-acting (sustained release) preparations will result in partial or complete nitrate tolerance. There are several proposed mechanisms which may contribute to the development of tolerance includ ing activation of neurohormonal mechanisms, plasma volume expansion an d depletion of intracellular sulfhydryl cofactors. To avoid tolerance to long term nitrate therapy, regimens should be tailored to provide a 10- to 12-hour nitrate-free interval when possible. This means that a ntianginal prophylaxis can only be provided by nitrate therapy for som e portion of each day, and that some patients will develop an increase in angina in the nitrate-free intervals which will necessitate short term therapy with sublingual nitroglycerin or a similar preparation.