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Related Experiment Videos

Nitrate tolerance.

J O Parker

    The American Journal of Cardiology
    |December 27, 1985
    PubMed
    Summary

    Nitrate tolerance reduces medication effectiveness over time. Intermittent nitrate therapy, with planned withdrawal periods, may restore antianginal effects and improve angina management.

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    Area of Science:

    • Pharmacology
    • Cardiology

    Background:

    • Nitrate tolerance is a decreased response to nitrates requiring higher doses for effect.
    • Tolerance may stem from pharmacokinetic changes or reduced tissue sensitivity.
    • Current nitrate therapies (oral, ointment, patches) show waning efficacy with sustained use.

    Purpose of the Study:

    • To investigate the phenomenon of nitrate tolerance in antianginal therapy.
    • To evaluate the efficacy of different nitrate administration methods and dosing schedules.
    • To explore the potential of intermittent nitrate therapy for managing angina pectoris.

    Main Methods:

    • Reviewed studies on oral isosorbide dinitrate, long-acting isosorbide dinitrate ointment, and once-daily nitroglycerin patches.
    • Examined hemodynamic and antianginal effects during sustained nitrate administration.
    • Assessed transmucosal and transdermal nitroglycerin administration with varying washout periods.

    Main Results:

    • Sustained nitrate therapy leads to significant attenuation in both magnitude and duration of effect.
    • Stable 24-hour nitroglycerin blood levels may not be optimal for sustained efficacy.
    • Intermittent nitrate administration and transmucosal nitroglycerin with a washout period prevented tolerance development.

    Conclusions:

    • The concept of continuous 24-hour nitrate coverage may be flawed.
    • Intermittent nitrate therapy is a promising strategy to overcome tolerance and manage angina.
    • Transmucosal nitroglycerin administration without a significant washout period did not induce tolerance.

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