Nitrates have a place in the prophylactic treatment of patients with angina pectoris. Their efficacy is not in doubt. However, there may be some practical problems associated with their use, such as unreliable absorption, short duration of action, treatment-induced headache, development of nitrate tolerance and a suggested rebound phenomenon observed during intermittent dosing. This article discusses how many of these problems may be solved by selection of formulation as well as nitrate compound. Thus, the development of a controlled-release formulation producing sufficiently high nitrate plasma concentrations during part of the day, followed by a low nitrate level rather than a nitrate-free interval, seems to have the potential to prevent both nitrate tolerance and rebound phenomenon. This system would also offer a sufficiently long duration of action with a convenient once-daily dose regimen.
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