Mechanism of action of the cisapride-induced vasodilatation in renal vasculature of rat.

BACKGROUND & OBJECTIVES: Cisapride is a prokinetic agent with cholinomimetic and 5-HT4 receptor agonistic properties. It has been proposed that cisapride-induced hypotension is partly mediated by cholinergic system. The aim of this study was to investigate the mechanism of cisapride-induced dilatation in the rat isolated perfused kidney. METHODS: Left kidneys of Wistar rats were isolated and perfused via renal artery and the perfusion pressure was recorded. Cisapride given as bolus injections (10(-10)-3x10(-5) mol/l) produced dose-dependent dilatations. Perfusion of antagonists or inhibitors was started 30min before the onset of phenylephrine perfusion. RESULTS: 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; blocker of M1, and M3 muscarinic receptors; 10(-7) mol/l) inhibited the responses to the lower doses of cisapride while, dextran (10(-7) mol/l), glibenclamide (inhibitor of ATP-sensitive potassium channels; 10(-5) mol/l) and capsaicin (for neuromediator depletion; 10(-6) mol/l) inhibited those to the higher doses. Dilatations induced by most of the doses of cisapride were inhibited by atropine (non-selective muscarinic receptor antagonist; 10(-7) mol/l), methylene blue (inhibitor of soluble guanylate cyclase; 10(-5) mol/l), 1H-[1,2,4] oxadiazolo-[4,3-a] Quinoxalin-1-One (ODQ; inhibitor of soluble guanylate cyclase; 10(-5) mol/l), and NG-nitro-L-arginine (L-NOARG; NO synthase inhibitor; 10(-4) mol/l). Inhibition induced by L-NOARG was reversed by L-arginine (10(-3) mol/l). The dilatation induced by cisapride was not affected by GR113808 (5-HT4 receptor antagonist; 10(-7) mol/l) and indomethacin (cyclooxygenase inhibitor; 10(-5) mol/l). INTERPRETATION & CONCLUSION: The findings indicated that cisapride caused vasodilatation through the release of nitric oxide (NO) as a result of the release of a substance acting on muscarinic receptors, in the renal vascular bed of the rat. The role of 5-HT4 receptors and prostanoids seemed unlikely.

Effect of erythromycin and cisapride on emptying of the vagally denervated intrathoracic stomach.

BACKGROUND: Subsequent to esophagectomy and reconstruction among patients with esophageal cancers, the intrathoracic denervated stomach acts as a passive conduit without peristalsis. OBJECTIVE: The study was designed to assess the impact of two prokinetic drugs viz. erythromycin and cisapride on the emptying of vagally denervated intrathoracic stomach. METHODS: Twenty consecutive patients of carcinoma esophagus, who had undergone one stage transhiatal oesophagectomy with cervical esophagogastrostomy and were disease free at three months postoperative follow-up, were included in the study. These patients were randomised into two groups of ten each. The patients in group A received erythromycin, while patients in group B received cisapride. The gastric emptying was studied by scintigraphy, using a standard test meal containing 99m Tc sulphur colloid labelled 'IDLIS' [rice based radio labelled food] before and after the drug treatment. RESULTS: The pre and post treatment mean gastric half emptying time of the patients in the erythromycin group was 52.6 min and 49.7 min (p > 0.1) and in cisapride group it was 53.76 and 26.4 min respectively (p < 0.05). Intergroup comparison of the difference was not statistically significant. CONCLUSION: Cisapride is an effective prokinetic agent in the treatment of gastric stasis of the vagally denervated intrathoracic stomach.

La cisaprida no altera el intervalo Q-T prolongado en pacientes con cirrosis hepática / Cisapride does not modify prolonged Q-T interval in patients with liver cirrhosis

Background: Abnormal small bowel motility, observed in liver cirrhosis, can be reversed with cisapride. Since both cisapride and liver disease are associated with prolonged QT interval, the possibility of adverse cardiovascular effects might be expected with cisapride treatment in these patients. Aim: To evaluate QT interval and other electrocardiographic changes during long term treatment with cisapride in cirrhotic patients. Patients and methods: Forty seven cirrhotic patients were studied. Electrocardiogram was recorded and the QT interval corrected according to Bazzett's formula was determined (normal value <0.44 s). Seventeen patients were treated with cisapride, 10 mg tid for seven months and electrocardiographic controls were performed at the end of the treatment. Results: The mean corrected QT interval was 0.46 ñ 0.03 s (range 0.4-0.53). 34 patients (64 percent) had QTc prolongation (0.47 ñ 0,02 s). Statistically significant higher values of QTc were observed in patients at Child Pugh stage B and C compared to stage A. No statistically significant difference according to the etiology of liver disease, were observed. No changes in mean QTc duration were observed during cisapride treatment. Conclusions: In spite that a prolonged QTc was a frequent finding in our serie of selected patients, no cardiovascular adverse effects were observed with long term cisapride treatment

Refluxo gastroesofágico / Gastroesophageal reflux

Objetivo: Discutir aspectos clínicos, propedêuticos de refluxo gastroesofágico. Método: Foi realizada revisão da literatura especializada dos últimos 30 anos, através dos bancos de dados Lilacs e Medline. Resultados: O refluxo gastroesofágico constitui uma das principais causas de consultas ao gastroenterologista pediátrico. Na maioria das vezes, representa condição benigna caracterizada pela presença de regurgitações, que evolui satisfatoriamente com medidas gerais. O tratamento medicamentoso, quando necessário, é capaz de controlar as manifestações clínicas e prevenir complicações. A cirurgia está indicada para os casos que não respondem ao tratamento clínico adequado. Conclusões: No tratamento do refluxo gastroesofágico dieta e postura elevada devem ser recomendados sempre. A cisaprida, droga procinética mais utilizada, tem sido responsabilizada por casos de arritmia cardíaca, sendo prudente a sua substituição por outros medicamentos. Broncoespasmo ou sintomas e sinais sugestivoss de esofagite indicam o uso de drogas inibidoras da secreção ácida