sulindac and Heart-Failure

Renal function and excretion of water, salt, and the prostacyclin hydration product (6-keto-PGF1 alpha) were evaluated in 10 furosemide-treated patients with well-controlled congestive heart failure. Four doses of sulindac (200 mg b.i.d.) and naproxen (500 mg b.i.d.) were given every 12 hours in a double-blind crossover design. Naproxen significantly decreased the urinary excretion of water (19%), sodium (26%), chloride (26%), and 6-keto PGF1 alpha (76%) and decreased osmolal clearance (18%). No significant changes in these functions were observed in the patients receiving sulindac. Plasma renin activity, plasma aldosterone, freewater clearance, or clearance of furosemide did not change significantly with either treatment. Although the basal glomerular filtration rate (GFR) and renal plasma flow (RPF) were reduced, these patients with cardiac disease, with normal serum sodium concentration, did not have any further reduction of GFR or RPF despite naproxen-induced inhibition of renal prostacyclin synthesis. It is concluded that renal prostaglandins contribute to the natriuretic effect of oral furosemide in patients with compensated congestive heart failure. In this clinical setting, GFR and RPF are not critically dependent on intact renal PGI2 synthesis. The lack of effect on renal prostaglandin synthesis and the renal response to oral furosemide supports the concept of a renal sparing effect of sulindac.

Topics: Aged; Biological Transport; Body Water; Chronic Disease; Electrolytes; Female; Furosemide; Glomerular Filtration Rate; Heart Failure; Humans; Indenes; Kidney; Kidney Tubules; Naproxen; Prostaglandins; Renal Circulation; Renin; Sulindac

The objective of this investigation was to study the effects of the two NSAIDs sulindac and naproxen on renal hemodynamics and excretion of water, salt and the prostacyclin metabolite 6-keto-PGF1 alpha in patients with well controlled congestive heart failure. Ten elderly females with congestive heart failure treated with oral furosemide were given four doses of sulindac and naproxen every twelve hours after a control day in a double-blind cross-over fashion. Naproxen significantly decreased the urinary excretion of water (19%), sodium (26%), chloride (26%), 6-keto-PGF1 alpha (76%) and decreased osmolal clearance by 18%. Sulindac had no significant effect on those parameters. There were no significant changes in glomerular filtration rate, renal blood flow, plasma renin activity, plasma aldosterone, free-water clearance or clearance of furosemide with either treatment. We conclude that renal prostaglandins are involved in the control of sodium excretion and urinary volume in patients with congestive heart failure even if renal hemodynamics are unaffected. Sulindac seems to be a selective inhibitor of extrarenal cyclooxygenase and consequently an appropriate drug for patients who require both diuretics and anti-inflammatory therapy.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Chlorides; Clinical Trials as Topic; Diuresis; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Failure; Humans; Indenes; Kidney; Naproxen; Sodium; Sulindac

Ten patients with rheumatoid arthritis (RA) and concomitant heart failure were treated with either naproxen or sulindac in an open randomized study to study the drugs' effects on the urinary excretion of prostaglandins on the plasma renin level and on the renal function of the group. Both drugs were given for 14 days and caused a similar and marked decrease in renal excretion of the prostaglandins PGE2 and PGF2 alpha and in plasma renin in all patients. There was no significant effect on the diastolic blood pressure, the body weight or the 24-h creatinine clearance and the clinical effect on the joint symptoms was identical. We conclude that both sulindac and naproxen inhibit the renal prostaglandin synthesis in patients with RA.

Topics: Adult; Aged; Arthritis, Rheumatoid; Benzothiadiazines; Diuretics; Female; Heart Failure; Humans; Indenes; Kidney; Male; Middle Aged; Naproxen; Prostaglandins; Renin; Sodium Chloride Symporter Inhibitors; Sulindac

Integrity of renal prostaglandin synthesis is necessary to maintain renal cortical and medullary function in patients with kidney, heart and liver disease. A comparison of the biochemical effects of various non-steroidal anti-inflammatory drugs (NSAIDs) necessitates that renal prostaglandin synthesis, as reflected by urinary immunoreactive prostaglandin excretion, be assessed with proper attention to problems created by seminal fluid contamination, inadequate chromatographic separation of samples, and largely unknown cross reactivities of systemic eicosanoid metabolites with antibodies raised against primary prostaglandins. Most, but not all, clinical studies support the observation that conventional doses of sulindac, administered orally, do not inhibit renal prostaglandin synthesis or alter renal function. Caution is in order, however, about the use of any NSAID, including sulindac at conventional dosage, in patients with severe liver disease as the plasma levels of sulindac sulfide are increased and prolonged compared to patients with normal hepatic function. Furosemide-induced natriuresis is probably not prostaglandin-mediated, in contrast to increased in renal blood flow and renin release. Some NSAIDs can attenuate the efficacy of antihypertensive therapy. Inasmuch as sulindac does inhibit systemic vascular prostacyclin production, its lack of hypertensive effect vis-a-vis other NSAIDs argues in favor of the importance of intrarenal prostaglandin-dependent mechanisms in mediating the hemodynamic effects of non-selective cyclooxygenase inhibitors.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Arachidonic Acids; Coronary Disease; Female; Heart Failure; Hemodynamics; Humans; Hypertension; Kidney; Kidney Diseases; Liver Cirrhosis; Male; Middle Aged; Prostaglandins; Sulindac

In summary the present study shows that sulindac does not interfere with the action of furosemide in contrast to naproxen. Therefore, treatment of arthritic disorders with sulindac might be of advantage in elderly patients with cardiac failure.

Topics: Anti-Inflammatory Agents; Arthritis; Diuresis; Drug Interactions; Furosemide; Heart Failure; Humans; Kidney; Naproxen; Prostaglandins; Sulindac