Interaction of Diuretics and Non-Steroidal Anti-Inflammatory Drugs in Man

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Abstract
The influence of 4 diuretics on renal prostaglandins [PG] was investigated in a 2-part study (A and B): A, 24 normal subjects on a constant Na intake received frusemide (80 mg/day), hydrochlorothiazide (100 mg), triamterene (200 mg) or spironolactone (300 mg); B, the same subjects were pretreated for 3 days with indomethacin (150 mg/day), which was continued during the 3 day administration of the respective diuretics and during a 2 day post-diuretic period. In study A, only triamterene provoked a rise in urinary PGE2 and F2.alpha. (+ 474 .+-. 92%, P < 0.01, and +192 .+-. 7%, P < 0.01). In study B, PG were significantly inhibited in all subjects. After indomethacin, the natriuretic effect of frusemide and spironolactone was reduced by 80 .+-. 12% (P < 0.01) and 54 .+-. 11% (P < 0.001), whereas the natriuresis induced by hydrochlorothiazide and triamterene was unchanged. No correlation was found between urinary PGE2 and F2.alpha. and natriuresis. When triamterene was associated with indomethacin, 2 subjects developed reversible acute renal failure. Plasma renin activity and urinary aldosterone were stimulated by the 4 diuretics in study A, but their response was blunted in study B. Urinary antidiuretic hormone was not modified by diuretics but was suppressed by indomethacin. Diflunisal, a structurally unrelated non-steroidal antiinflammatory drug, given to 12 of the subjects provoked similar interactions with frusemide, hydrochlorothiazide and spironolactone. Evidently, PG contribute to the natriuretic effects of frusemide and spironolactone, but not to those of hydrochlorothiazide and triamterene.