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[Tolerance of treatment with nitrate derivatives]
R Isnard1, J M Aouate, D Thomas
1Service de cardiologie, hôpital Pitié-Salpêtrière, Paris.
Abstract:
Tolerance to treatment with nitrate derivatives, suspected for many years and often ignored in everyday clinical practice, has recently been the subject of much study. Although the phenomenon has been clearly demonstrated in patients on long-term therapy, it seems to vary from patient to patient, with the underlying pathology and the galenic form of nitrate used. The mechanism of tolerance to nitrates is multifactorial, related on the one hand to depletion of sulfhydryl groups in the body and on the other to activation of the sympathetic and renin-angiotensin systems. The administration of sulfhydryl groups in the form of N-acetylcysteine partially restores the effects of nitrates in some patients.
Insights
Tolerance to nitrate derivative treatments can occur in patients, varying by individual factors. Restoring sulfhydryl groups, such as with N-acetylcysteine, may help regain nitrate effectiveness.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
Context:
- Nitrate derivatives are widely used for cardiovascular conditions.
- Tolerance to nitrate therapy is a recognized clinical issue, though often underestimated.
- Long-term nitrate use can lead to diminished therapeutic effects.
Purpose:
- To explore the phenomenon of nitrate tolerance in patients undergoing long-term therapy.
- To investigate the multifactorial mechanisms underlying nitrate tolerance.
- To assess the potential of sulfhydryl group replenishment in mitigating nitrate tolerance.
Summary:
- Nitrate tolerance is a complex issue influenced by patient-specific factors, pathology, and drug formulation.
- Key mechanisms include depletion of bodily sulfhydryl groups and activation of sympathetic and renin-angiotensin systems.
- Administration of N-acetylcysteine, a source of sulfhydryl groups, has shown potential in partially restoring nitrate efficacy in some patients.
Impact:
- Highlights the clinical significance of nitrate tolerance and its variable presentation.
- Provides insights into the physiological mechanisms driving nitrate unresponsiveness.
- Suggests a potential therapeutic strategy, N-acetylcysteine, for managing nitrate tolerance in clinical practice.