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Tolerance development during isosorbide dinitrate treatment: can it be circumvented?
Zeitschrift Fur Kardiologie
|January 1, 1983
Summary
Tolerance develops with repeated use of isosorbide dinitrate (ISDN) for anti-ischemic effects, diminishing its long-term efficacy. Nitroglycerin (NTG) effectiveness is reduced but not negated during chronic ISDN treatment.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Ischemic heart disease management often involves nitrates.
- Understanding nitrate tolerance is crucial for optimizing anti-ischemic therapy.
Purpose of the Study:
- To evaluate the anti-ischemic effects of isosorbide dinitrate (ISDN) and nitroglycerin (NTG).
- To assess the impact of acute and chronic administration on efficacy.
- To investigate potential nitrate tolerance during ISDN treatment.
Main Methods:
- Randomized, double-blind, crossover, placebo-controlled studies.
- Administration of ISDN (40 mg QID, 20 mg BID) and sublingual NTG (0.8 mg).
- Measurement of ST-segment depression and nitrate consumption.
Main Results:
- Acute ISDN (40 mg) significantly reduced ST depression; chronic use showed no significant effect, indicating tolerance.
- Sublingual NTG reduced ST depression acutely and during chronic ISDN, but its efficacy was diminished.
- Twice-daily ISDN (20 mg) maintained anti-ischemic effects and reduced anginal attacks and nitrate use.
Conclusions:
- Tolerance develops with repeated ISDN administration, impacting its long-term anti-ischemic effectiveness.
- NTG effectiveness is reduced, not eliminated, when used concurrently with chronic ISDN.
- Twice-daily ISDN dosing may mitigate tolerance development compared to four-times-daily dosing.