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[Nitrate tolerance].

¹Medizinische Klinik Stadtspital Triemli, Zürich.

Schweizerische Medizinische Wochenschrift

|December 17, 1988

Summary

This summary is machine-generated.

Nitrate tolerance reduces the effectiveness of continuous nitrate medication. Intermittent nitrate use or alternative therapies like beta-blockers can prevent tolerance and improve anti-ischemic effects.

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Area of Science:

Pharmacology
Cardiovascular Medicine

Context:

Continuous nitrate therapy can lead to nitrate tolerance, diminishing hemodynamic and anti-ischemic effects.
This tolerance can manifest as pseudotolerance (volume/salt retention, counter-regulatory mechanisms) or true pharmacological tolerance.
Changes in nitrate pharmacokinetics play a lesser role compared to cellular mechanisms.

Purpose:

To define nitrate tolerance and elucidate the mechanisms behind its development.
To explore the distinction between pseudotolerance and true pharmacological tolerance.
To provide recommendations for optimizing nitrate therapy and preventing tolerance.

Summary:

Nitrate tolerance involves reduced effectiveness due to pseudotolerance (hemodynamic shifts) and true tolerance (cellular mechanisms like impaired guanylate cyclase activity).

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Mechanisms of true tolerance include diminished cellular uptake, reduced intracellular SH groups, inhibited guanylate cyclase, and stimulated phosphodiesterase, leading to decreased cyclic GMP.

Intermittent nitrate administration is proposed to prevent tolerance by allowing periods of low nitrate levels.

Impact:

Understanding nitrate tolerance mechanisms is crucial for effective cardiovascular drug therapy.
Intermittent nitrate use or alternative agents (beta-blockers, calcium antagonists) may be superior for sustained anti-ischemic action.
Strategic use of nitrates during peak ischemia risk, combined with other agents, can optimize patient outcomes.