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Tolerance development as a pharmacological and clinical problem.

K E Andersson

    Acta Pharmacologica Et Toxicologica
    |January 1, 1986
    PubMed
    Summary

    Pharmacological tolerance, both dispositional and pharmacodynamic, arises from adaptive receptor changes. Beta-adrenoceptor alterations exemplify mechanisms of tolerance to agonists used for asthma and heart failure.

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    Area of Science:

    • Pharmacology
    • Molecular Biology
    • Drug Metabolism

    Background:

    • Acquired pharmacological tolerance presents as dispositional (pharmacokinetic) or pharmacodynamic forms.
    • Pharmacodynamic tolerance is frequently linked to adaptive receptor alterations.
    • Beta-adrenoceptors serve as a well-established model for studying tolerance mechanisms.

    Purpose of the Study:

    • To discuss the mechanisms underlying tolerance to adrenoceptor agonists.
    • To explore tolerance development to adrenoceptor agonists and other agents.
    • To examine the role of these mechanisms in treating asthma, uterine hyperactivity, and congestive heart failure.

    Main Methods:

    • Review of existing literature on pharmacological tolerance.
    • Analysis of adaptive receptor changes, particularly beta-adrenoceptors.
    • Examination of clinical applications and implications for therapeutic agents.

    Main Results:

    • Pharmacodynamic tolerance is commonly mediated by adaptive receptor modifications.
    • Beta-adrenoceptor changes provide a robust model for understanding tolerance.
    • Tolerance mechanisms are relevant to treatments for conditions like asthma and heart failure.

    Conclusions:

    • Adaptive receptor changes are central to pharmacodynamic tolerance.
    • Understanding these mechanisms is crucial for optimizing drug efficacy.
    • Further research into tolerance is warranted for improved therapeutic strategies.

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