Abstract
Tolerance to long-term nitrate therapy has now been documented in a large number of clinical studies. These trials have demonstrated attenuation of effect over time but a return of responsiveness with the start of nitrate-free intervals. Intermittent therapy prevents attenuation or tolerance when used as the initial treatment regimen. This strategy is appropriate for use with isosorbide dinitrate, as well as intravenous or transdermal nitroglycerin. Transmucosal nitroglycerin has not been associated with tolerance; the lack of such an effect may be a result of rapid increases and decreases in drug levels. In the future, sulfhydryl donors may also prove useful in prevention or reversal of nitrate tolerance.
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