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Interaction between nonsteroidal anti-inflammatory drugs and loop diuretics: modulation by sodium balance
A Herchuelz1, F Derenne, F Deger
1Unit of Clinical Pharmacology, Hôpital Universitaire André Vésale, Montigny-le-Tilleul, Belgium.
Summary
Nonsteroidal anti-inflammatory drugs like indomethacin can reduce the effectiveness of loop diuretics, such as torasemide. This interaction is more pronounced in individuals on low-sodium diets, impacting kidney function and fluid balance.
Area of Science:
- Nephrology
- Pharmacology
- Internal Medicine
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) can interfere with loop diuretics' natriuretic effects.
- Previous studies show mixed results regarding NSAID interactions with torasemide, a newer loop diuretic.
Purpose of the Study:
- To investigate the effect of indomethacin on torasemide-induced natriuresis in healthy volunteers under varying sodium intake levels.
- To determine if sodium balance influences the interaction between indomethacin and torasemide.
Main Methods:
- Six healthy volunteers participated in the study.
- Two sodium intake levels (50 and 150 mEq/day) were used.
- The natriuretic response to two doses of torasemide was assessed with and without indomethacin administration.
Main Results:
- Indomethacin significantly reduced the natriuretic response to torasemide under a low-sodium diet.
- Indomethacin did not affect the natriuretic response to torasemide under a normal-sodium diet.
- Indomethacin similarly reduced plasma renin activity, angiotensin II levels, and prostaglandin excretion under both sodium conditions.
Conclusions:
- Indomethacin reduces the natriuretic response to torasemide in humans.
- Dietary sodium restriction is a key factor in the interaction between NSAIDs and loop diuretics.
- The interaction may involve NSAID-induced blockade of diuretic-induced increases in renal blood flow, particularly under sodium restriction.