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Related Experiment Videos

[Long-term therapy with nitrates. Relation between dosage and tolerance effect].

M Tauchert, W Jansen, M Metternich

    Herz
    |June 1, 1984
    PubMed
    Summary
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    Low doses of isosorbide dinitrate (ISDN) and isosorbide 5-mononitrate (5-ISMN) effectively improve exercise capacity in coronary artery disease patients long-term. High doses, however, showed reduced effectiveness over time.

    Area of Science:

    • Cardiology
    • Pharmacology

    Background:

    • Coronary artery disease (CAD) management often involves nitrates.
    • Understanding nitrate tolerance is crucial for effective treatment.

    Purpose of the Study:

    • To assess the long-term effects of isosorbide dinitrate (ISDN) and isosorbide 5-mononitrate (5-ISMN) on exercise hemodynamics and capacity in CAD patients.
    • To investigate dose-dependent nitrate tolerance.

    Main Methods:

    • 56 patients with CAD were studied.
    • Hemodynamic parameters (mean pulmonary artery pressure) and exercise capacity (work capacity) were measured.
    • Patients received either ISDN or 5-ISMN at different doses (20 mg, 60 mg ISDN / 50 mg 5-ISMN) for acute and long-term assessments.

    Main Results:

    Related Experiment Videos

    • Both ISDN and 5-ISMN (20 mg) significantly reduced pulmonary artery pressure and increased exercise capacity acutely and long-term without tolerance.
    • Higher doses (60 mg ISDN / 50 mg 5-ISMN) showed acute benefits but significant attenuation of effects after four weeks, indicating tolerance.
    • No substantial difference in acute effects between standard and higher doses.

    Conclusions:

    • Standard doses of ISDN and 5-ISMN are effective for long-term management of exercise hemodynamics and capacity in CAD.
    • High-dose nitrate therapy may lead to tolerance, diminishing therapeutic benefits.
    • The mechanism of high-dose nitrate tolerance is complex, involving pharmacokinetic, pharmacodynamic, and adaptive factors.