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Rationale for intermittent nitrate therapy.

E A Amsterdam1

  • 1Department of Internal Medicine, University of California, School of Medicine, Davis.

The American Journal of Cardiology
|November 27, 1992
PubMed
Summary
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Nitrate tolerance, a reduced response to nitrate therapy, is common with continuous dosing. Intermittent nitrate dosing prevents tolerance by allowing a nitrate-free interval, restoring drug effectiveness.

Area of Science:

  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Tolerance to nitrate therapy is a well-established phenomenon.
  • This tolerance manifests as a decreased response or increased dosage requirement for nitrates.
  • It occurs with continuous nitrate administration via oral, intravenous, or transdermal routes.

Purpose of the Study:

  • To review the established tolerance to nitrate therapy.
  • To discuss strategies for preventing nitrate tolerance.
  • To highlight the benefits of intermittent nitrate dosing.

Main Methods:

  • Literature review on nitrate tolerance.
  • Analysis of continuous vs. intermittent nitrate dosing regimens.
  • Discussion of mechanisms underlying nitrate tolerance and recovery.

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Main Results:

  • Nitrate tolerance develops rapidly and is typically partial.
  • Continuous nitrate therapy leads to tolerance.
  • Intermittent nitrate dosing prevents tolerance and restores vascular responsiveness.

Conclusions:

  • Intermittent nitrate dosing, with a 8-12 hour nitrate-free interval, is an effective strategy to prevent nitrate tolerance.
  • This approach restores metabolic mechanisms responsible for nitrate efficacy.
  • Intermittent therapy offers a convenient outpatient management strategy.