misoprostol and Liver-Cirrhosis--Alcoholic

Misoprostol (200 micrograms) has been shown to acutely counteract the indomethacin-induced renal dysfunction in well compensated cirrhotic patients. The aim of this study was to determine if the prophylactic value of misoprostol was dose-dependent. Parameters of renal hemodynamics and tubular sodium and water handling were assessed by clearance techniques in 26 well compensated cirrhotic patients before and after an oral combination of 50 mg of indomethacin and various doses of misoprostol. The 200-micrograms dose was able to totally abolish the deleterious renal effects of indomethacin, whereas the 800-micrograms dose resulted in significant worsening of renal hemodynamics and sodium retention. These changes were maximal in the hour immediately after medications and slowly returned toward base-line levels thereafter. These results suggest that the renal protective effects of misoprostol is dose-dependent. However, until this apparent ability of 200 micrograms of misoprostol to prevent the adverse effects of indomethacin on renal function is confirmed with chronic frequent dosing, it would be prudent to avoid nonsteroidal anti-inflammatory therapy in patients with cirrhosis.

Topics: Diuresis; Dose-Response Relationship, Drug; Female; Glomerular Filtration Rate; Humans; Indomethacin; Kidney; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Misoprostol; Renal Plasma Flow, Effective

Indomethacin has been shown to have adverse effects on renal function in patients with well-compensated alcoholic cirrhosis. The aim of this study was to determine whether an oral prostaglandin E1 analogue, misoprostol, could prevent this indomethacin-induced renal dysfunction.. Six patients with well-compensated alcoholic cirrhosis were studied. Renal hemodynamics and tubular function were assessed by clearance techniques before and after an oral dose of (i) 50 mg of indomethacin alone (I50), and (ii) a combination of I50 and 200 micrograms of misoprostol.. I50 produced a significant reduction in glomerular filtration rate, a fall in effective renal plasma flow and an increase in renal vascular resistance. Two hundred micrograms of misoprostol was able to abolish the deleterious renal effects of indomethacin totally, yielding an increase in glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance as well as an increase in urinary volume and urinary sodium excretion. These beneficial effects were maximal in the hour immediately following medication, but were only transient, and this may be a limiting factor in its clinical use.. If the beneficial renal effects of misoprostol could be confirmed after chronic administration, then the vasodilatory, natriuretic and diuretic potential of 200 micrograms of misoprostol could be of potential therapeutic value in patients with well-compensated alcoholic cirrhosis who require non-steroidal anti-inflammatory drug therapy.

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents, Non-Steroidal; Drug Interactions; Drug Therapy, Combination; Glomerular Filtration Rate; Hemodynamics; Humans; Indomethacin; Kidney; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Misoprostol; Prostaglandins, Synthetic; Renal Insufficiency; Sodium; Vascular Resistance

Prostaglandins are important modulators of renal physiology, particularly when the effective circulatory volume is decreased. The aim of this study was to determine the dose-dependent effects of an oral prostaglandin E1 analogue, misoprostol, on renal function in patients with well-compensated alcoholic cirrhosis.. Renal hemodynamics and tubular function were assessed by clearance techniques, before and after 100-microgram, 200-microgram, 400-microgram, or 800-microgram oral doses of misoprostol.. Overall, the results indicate that low-dose misoprostol is vasodilatory, natriuretic, and diuretic whereas high-dose misoprostol increases renal vascular tone and inhibits sodium and water excretion. The 200-microgram dose produced a transient but significant increase in the glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance. Urinary volume and urinary sodium excretion increased and urinary osmolality decreased.. The results suggest that, in patients with well-compensated cirrhosis, the renal effects of misoprostol are determined by a bell-shaped dose-response curve. The renal vasodilatory, natriuretic, and diuretic potential of 200-micrograms of misoprostol suggests that it may be of therapeutic value in patients with cirrhosis.

Topics: Administration, Oral; Body Water; Dose-Response Relationship, Drug; Female; Hemodynamics; Humans; Kidney; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Misoprostol; Renal Circulation; Sodium