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Tolerance, rebound, and time-zero effect of nitrate therapy
1Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York.
The American Journal of Cardiology
|November 27, 1992
Summary
Continuous use of nitroglycerin patches for angina can lead to tolerance, reducing effectiveness. Intermittent use shows promise but requires further research to optimize dosing and avoid rebound symptoms.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Nitroglycerin and long-acting nitrates are effective for acute anginal pain.
- Tolerance development with continuous use of these agents is a growing concern.
Purpose of the Study:
- To investigate the efficacy and tolerance of transdermal nitroglycerin therapy.
- To explore optimal intermittent dosing strategies for sustained therapeutic effects.
Main Methods:
- Pilot study and a larger Transdermal Nitroglycerin Cooperative Study were conducted.
- Evaluated continuous high-dose transdermal nitroglycerin therapy.
- Assessed intermittent transdermal nitroglycerin use (12 hours on, 12 hours off).
Main Results:
- Continuous transdermal nitroglycerin therapy demonstrated tolerance, attenuating therapeutic effects.
- Tolerance was observed within 24 hours of continuous patch initiation.
- Intermittent use achieved sustained pharmacologic activity, but discontinuation led to rebound anginal symptoms and reduced exercise tolerance.
Conclusions:
- Continuous transdermal nitroglycerin therapy is limited by rapid tolerance development.
- Intermittent dosing strategies may sustain therapeutic benefits but require careful optimization.
- Further clinical research is essential to establish optimal intermittent dosing for managing angina and preventing rebound effects.