RESUMO
Prokinetic agents are a very large family of drugs with different mechanisms of action. Only QT prolongation by cisapride has made notable impact and deserved its partial restriction and/or withdrawal from the market. Postmarketing surveillance initially showed that cisapride was generally safe and well tolerated, but in the past decade, more recent data have shown some risk in the patient populations. QT prolongation by prokinetic agents can raised from different mechanisms: some involve increased plasma concentrations of cisapride due to increased bioavailability by inhibiting P glycoprotein, and inhibition of metabolism or deficit in the elimination. On the other hand, pharmacodynamic interactions can also enhance the arrhythmogenic effect of cisapride. The present article presents the mechanisms and reviews the main interactions studied so far, and the role of pharmacovigilance in the detection of rare clinical events. We emphasize the need for physicians to look for conditions (either clinical or not) prone to increase the risk of QT interval prolongation.
Assuntos
Cisaprida/efeitos adversos , Fármacos Gastrointestinais/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Sistemas de Notificação de Reações Adversas a Medicamentos , Animais , Disponibilidade Biológica , Cisaprida/farmacocinética , Interações Medicamentosas , Fármacos Gastrointestinais/farmacocinética , Humanos , Fatores de Risco , Agonistas do Receptor de Serotonina/efeitos adversos , Agonistas do Receptor de Serotonina/farmacocinéticaRESUMO
La cisaprida es hasta hoy el procinético intestinal de mayor uso en el mundo para el tratamiento de los trastornos de motilidad gastrointestinal, en México disponible de 1987 a la fecha, la farmacocinética y farmacodinámica han cobrado inusitada importancia al reportarse efectos adversos cardiacos potencialmente mortales (arritmias) principalmente con el uso combinado con medicamentos metabolizados por el citocromo P450 fracción 3 A4 en los que se incluye una larga lista de antibióticos, antimicóticos, antihistamínicos, antiarrítmicos etc, aún más el 24 de marzo de 2000 en Estados Unidos Janssen Pharmaceuticals y la FDA emitieron un comunicado para el uso restringido de la cisaprida. En nuestro país es posible que en un futuro cercano se haga lo mismo.