RESUMO
BACKGROUND & AIMS: The critical role of cyclooxygenase (COX) products in maintenance of renal function in cirrhosis with ascites discourages the use of nonsteroidal anti-inflammatory drugs in this disease. The recent development of selective COX-2 inhibitors opens new avenues for the use of these compounds in decompensated cirrhosis. The current study evaluates the effects of a selective COX-2 inhibitor (SC-236) on renal function in cirrhotic rats with ascites. METHODS: In protocol 1, urine volume, urinary excretion of sodium and prostaglandins, glomerular filtration rate, and renal plasma flow were measured before and after administration of SC-236 (n = 12) or ketorolac (n = 10) to rats with cirrhosis. Protocol 2 was aimed at assessing the effects of COX inhibitors on renal water metabolism in 28 cirrhotic rats. RESULTS: Administration of SC-236 to cirrhotic animals did not produce significant renal effects, whereas administration of the nonselective COX-1/COX-2 inhibitor, ketorolac, resulted in a marked reduction in urine volume, urinary excretion of prostaglandins, and glomerular filtration rate and in a significant impairment in renal water metabolism. CONCLUSIONS: These findings indicate that SC-236 does not significantly impair renal function in rats with cirrhosis.
Assuntos
Ascite/complicações , Isoenzimas/metabolismo , Rim/fisiologia , Cirrose Hepática Experimental/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/biossíntese , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Animais , Água Corporal/metabolismo , Tetracloreto de Carbono , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Cetorolaco , Rim/efeitos dos fármacos , Rim/metabolismo , Testes de Função Renal , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/complicações , Masculino , Proteínas de Membrana , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Tolmetino/análogos & derivados , Tolmetino/farmacologia , UrinaRESUMO
A sample of 120 patients, all of whom met DSM-III criteria for major unipolar depressive disorder, were randomly allocated to two treatment groups. Sixty patients were treated with fluoxetine and 60 with clomipramine during a 6-week period. No significant difference was found in antidepressant efficacy, with improvement occurring on both drugs. Important differences were found in the side-effects profile of each group, their incidence being significantly lower and tending to disappear during the course of treatment in the group of patients treated with fluoxetine.
