Nitrate therapy and the development of tolerance

The efficacy of organic nitrates in the treatment of acute episodes of angina pectoris is unquestioned. However, long-term use of these agents is associated with the development of tolerance or of reduced efficacy over time when given in doses or formulations that maintain therapeutic blood levels for 24-hour periods. Thus, the role of long-term use of nitrates in prophylactic treatment of stable angina has been questioned. The purpose of this brief review is to evaluate nitrate tolerance, a key issue in the prophylactic use of nitrates, as well as to review what is known about clinical rebound. These issues are discussed, and ways of preventing tolerance development are explored. Intermittent therapy involving a dose-free interval during each 24-hour period helps prevent tolerance.