RESUMO
Twenty-nine patients with recent myocardial infarction were randomly allocated to a placebo group (n = 14) and to a group (n = 15) who received sulphinpyrazone, 4 x 200 mg daily for 7 days. Renal function significantly and transiently deteriorated in the sulphinpyrazone group compared to the placebo group. In the sulphinpyrazone group the 24 hour-urinary prostaglandin E2 and kallikrein excretion were suppressed. These data suggest that the decrease in renal function caused by sulphinpyrazone early after myocardial infarction could be mediated by an inhibition of renal prostaglandin and/or kallikrein-kinin synthesis.
Assuntos
Rim/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Sulfimpirazona/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Idoso , Ensaios Clínicos como Assunto , Creatinina/sangue , Método Duplo-Cego , Feminino , Humanos , Calicreínas/urina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Prostaglandinas E/urina , Distribuição Aleatória , Sulfimpirazona/uso terapêuticoRESUMO
Sulphinpyrazone administered acutely to 8 healthy male volunteers decreased the urinary (U) excretion of prostaglandin (PG)E2 (p less than 0.01)( but not of PGF2 alpha. Also, the ratio U-PGE2/U-PGF2 alpha and the urinary excretion of kallikrein declined (p less than 0.001 and p less than 0.05 respectively). Sulphinpyrazone therapy caused a significant inhibition of PRA (p less than 0.05). Renal function, as assessed by serum creatinine and creatinine clearance, remained constant in these normal men, possibly related to the fact that both the vasodilatory PG-kallikrein-kinin system and the vasoconstrictive renin-angiotensin system were inhibited by sulphinpyrazone. However, it is conceivable that in clinical situations where vasoconstrictive stimuli are enhanced, sulphinpyrazone can disturb the balance between those systems and can lead to an impaired renal function.
Assuntos
Calicreínas/fisiologia , Prostaglandinas/fisiologia , Renina/fisiologia , Sulfimpirazona/farmacologia , Adulto , Creatinina/sangue , Humanos , Masculino , Fatores de TempoRESUMO
A double-blind, placebo-controlled trial was performed to determine the therapeutic efficacy of cisapride in patients with refractory functional dyspepsia. A total of 147 patients with functional dyspepsia characterized by prominent epigastric pain or discomfort were randomized to 2 weeks' treatment with metoclopramide or domperidone (both 30 mg/day); of these, 53 patients unresponsive to dopamine antagonist treatment were randomized to cisapride 30 mg/day or placebo for an additional 2 weeks. Metoclopramide and domperidone produced comparable alleviation of epigastric symptoms; global efficacy was good or excellent in 62% and 57% of patients, respectively. In refractory patients, cisapride tended to display greater efficacy than placebo against epigastric pain, particularly at night. Global assessments of efficacy significantly favored cisapride over placebo, with good or excellent ratings in 65% and 32% of patients, respectively. Cisapride was well tolerated. Thus, cisapride appears to be an effective agent in functional dyspepsia unresponsive to other gastrokinetic agents.
Assuntos
Domperidona/uso terapêutico , Dispepsia/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Metoclopramida/uso terapêutico , Piperidinas/uso terapêutico , Adolescente , Adulto , Idoso , Doença Crônica , Cisaprida , Método Duplo-Cego , Dispepsia/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The effects of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome (IBS) were evaluated in a randomized, double-blind, placebo-controlled study. Sixty-nine IBS patients were assigned to a 12-week treatment with either 5 mg cisapride or placebo t.i.d.; this dosage could be changed if necessary. The mean weekly number of days on which a stool was passed in the cisapride and placebo group increased to 5.3 and 4.4 (p less than 0.05) during weeks 8-12 of treatment, and the number of days with stools of normal consistency increased to 3.5 and 1.9 (p less than 0.05), respectively. At week 12, the reduction in severity and frequency scores for abdominal pain was significantly greater (p less than or equal to 0.05) in the cisapride group (60 and 61%) than in the placebo group (40 and 32%), as it was for abdominal distension (p less than 0.05). Cisapride tended to be better than placebo in diminishing flatulence. In 71% versus 39% of the patients the overall rating for the response to treatment was good or excellent at week 12. Cisapride was well tolerated. These results suggest that the drug will be useful for the management of constipation-predominant IBS.
Assuntos
Doenças Funcionais do Colo/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Piperidinas/uso terapêutico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Adolescente , Adulto , Idoso , Cisaprida , Doenças Funcionais do Colo/complicações , Doenças Funcionais do Colo/fisiopatologia , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/etiologia , Defecação/efeitos dos fármacos , Método Duplo-Cego , Feminino , Flatulência/tratamento farmacológico , Flatulência/etiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We report on 4 cases of reversible acute renal failure (ARF), appearing within the first days after institution of a sulfinpyrazone treatment (600 mg p. day) early after a myocardial infarction. Urinary data were consistent with an acute tubular necrosis. A renal biopsy, performed in 3 patients, revealed only very discrete tubular and interstitial lesions, not helpful in the understanding of the ARF. Three pathogenetic mechanisms could be evoked. Data in favour of an acute tubular precipitation of uric acid or an immunologically induced acute interstitial nephritis are lacking. More probably this ARF is due to an inhibitory effect of sulfinpyrazone on the renal prostaglandin synthesis. Early after a myocardial infarction, renal prostaglandins could play an important protective role in maintaining the renal circulation. Renal function should be monitored closely when sulfinpyrazone is prescribed, especially early after a myocardial infarction.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Sulfimpirazona/efeitos adversos , Injúria Renal Aguda/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Sulfimpirazona/uso terapêuticoRESUMO
Using a double-blind procedure, 29 patients with a recent myocardial infarction were randomly allocated to a placebo group (n = 14) and to a group receiving aspirin, 300 mg three times a day (n = 15) over 7 days. No change in renal function was observed in either treatment group. Compared with the placebo group, the 24-h urinary excretion of prostaglandin E2 (PGE2) was significantly suppressed in the aspirin group, but the urinary kallikrein activity was unchanged. These results contrast with our previous study of similar patients, in which sulfinpyrazone decreased renal function, as well as the urinary PGE2 and kallikrein excretions. These divergent effects of aspirin and sulfinpyrazone on urinary kallikrein activity could explain the different trends in renal function observed early after myocardial infarction.