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Risk of rebound phenomenon during nitrate withdrawal
1Department of Cardiology, Niguarda Hospital, Milan, Italy.
Abstract:
Organic nitrates are first-line drugs in the therapy and prevention of angina. These compounds, are acutely effective yet some formulations demonstrate a rapid decline in effect with chronic use. In this review the mechanisms of development of nitrate tolerance and the different strategies to prevent it are considered. If frequent dosing, high dosages and long acting preparations giving constant 24 h plasma GTN levels are more likely to cause tolerance, nitrate-low periods seem to be effective in restoring the drug's efficacy. Intermittent therapy with GTN patches, an effective way to prevent tolerance, raises the problem of the rebound phenomenon during the removal period. Considerable variations in its occurrence have been reported and in this review the factors that may influence the incidence of the rebound are discussed. The dangers of rebound can be lessened by concomitant anti-anginal drugs or avoiding any abrupt decline in blood nitrate concentrations. The use of beta-blockers or calcium channel blockers during intermittent therapy with GTN patches and oral preparations of isosorbide dinitrate or isosorbide 5-mononitrate seem to be effective for this purpose.
Insights
Organic nitrates effectively treat angina but can cause tolerance with continuous use. Intermittent therapy and other strategies can prevent tolerance and manage rebound effects, restoring drug efficacy.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
Background:
- Organic nitrates are primary treatments for angina.
- Chronic use of some nitrate formulations leads to decreased effectiveness (tolerance).
Purpose of the Study:
- To review mechanisms of nitrate tolerance.
- To discuss strategies for preventing nitrate tolerance and managing rebound phenomena.
Main Methods:
- Literature review on organic nitrate therapy.
- Analysis of factors influencing nitrate tolerance and rebound.
- Evaluation of preventative strategies for intermittent therapy.
Main Results:
- Constant 24-hour plasma levels from frequent dosing or long-acting preparations increase tolerance risk.
- Nitrate-low periods can restore drug efficacy.
- Intermittent therapy, while preventing tolerance, may cause rebound upon removal.
Conclusions:
- Nitrate tolerance is linked to dosing frequency and duration.
- Intermittent therapy and nitrate-low periods are key to maintaining efficacy.
- Concomitant medications like beta-blockers or calcium channel blockers can mitigate rebound effects.