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Nitrate tolerance in angina therapy. How to avoid it

J D Rutherford1

  • 1University of Texas Southwestern Medical Center at Dallas, USA.

Drugs
|February 1, 1995
PubMed
Summary

Nitrate tolerance, a loss of medication effectiveness, occurs with frequent or continuous organic nitrate use. To maintain efficacy, nitrate therapy should include a daily nitrate-free interval to avoid tolerance.

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Area of Science:

  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Organic nitrates are crucial for managing angina.
  • Long-term administration can lead to tolerance, diminishing therapeutic effects.

Purpose of the Study:

  • To define nitrate tolerance and its mechanisms.
  • To provide strategies for optimizing long-term nitrate therapy.

Main Methods:

  • Review of existing literature on organic nitrate pharmacology.
  • Analysis of proposed mechanisms contributing to nitrate tolerance.

Main Results:

  • Frequent dosing, continuous delivery systems, or sustained-release preparations of long-acting nitrates induce tolerance.
  • Proposed mechanisms include neurohormonal activation, plasma volume changes, and altered sulfhydryl cofactor levels.

Conclusions:

  • Nitrate tolerance is a significant challenge in long-term antianginal therapy.
  • Tailoring regimens with a 10-12 hour nitrate-free interval can mitigate tolerance.
  • Short-term sublingual nitroglycerin may be needed during nitrate-free intervals.

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