Effects of nonsteroidal anti-inflammatory drugs in healthy subjects.
Nonsteroidal anti-inflammatory drugs inhibit cyclo-oxygenase activity and thereby reduce prostaglandin synthesis. Studies in humans have used these cyclo-oxygenase inhibitors to examine the role of prostaglandins in controlling renal function. Although short-term studies have demonstrated reductions in effective renal plasma flow, glomerular filtration rate, urinary sodium excretion, and plasma renin activity, long-term administration of nonsteroidal anti-inflammatory drugs does not result in significant or clinically important changes in renal function in normal human subjects. If healthy volunteers are placed on low-sodium diets or treated with diuretics, both renal hemodynamics and salt and water excretion can become prostaglandin-dependent. Studies in normal subjects suggest that sulindac, a nonsteroidal anti-inflammatory drug that undergoes biotransformation in the kidney, does not inhibit renal prostaglandin synthesis or urinary sodium excretion under basal conditions but may impair furosemide-stimulated prostaglandin synthesis and changes in renal function. Doses of sulindac that spare basal renal cyclo-oxygenase do inhibit extrarenal cyclo-oxygenase. The mechanism responsible for this biochemical selectivity of sulindac is not related to a differential sensitivity of the renal cyclo-oxygenase to the active metabolite of sulindac, sulindac sulfide. Sulindac sulfide, in concentrations as low as 1 nM, was equipotent to indomethacin as an inhibitor of prostaglandin E2 synthesis in primary cultures of three renal cell lines. Appropriate clinical use of all nonsteroidal anti-inflammatory drugs, including sulindac, requires careful consideration of risk factors that predispose to nephrotoxicity and careful monitoring when administered to patients at risk.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000633:toxicity; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001834:Body Water / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000139:chemically induced; D011453:Prostaglandins / Q000096:biosynthesis / Q000494:pharmacology; D012083:Renin / Q000097:blood; D013467:Sulindac / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D004573:Electrolytes; D011453:Prostaglandins; D013467:Sulindac; D016718:Arachidonic Acid; D012083:Renin