Abstract
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.
Keywords: Prokinetic agents, cisapride, mosapride, torsades de pointes, long QT syndrome, pharmacovigilance
Current Drug Safety
Title: Prokinetic Agents and QT Prolongation: A Familiar Scene with New Actors
Volume: 5 Issue: 1
Author(s): Guillermo Alberto Keller and Guillermo Di Girolamo
Affiliation:
Keywords: Prokinetic agents, cisapride, mosapride, torsades de pointes, long QT syndrome, pharmacovigilance
Abstract: 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.
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Cite this article as:
Keller Alberto Guillermo and Di Girolamo Guillermo, Prokinetic Agents and QT Prolongation: A Familiar Scene with New Actors, Current Drug Safety 2010; 5 (1) . https://dx.doi.org/10.2174/157488610789869166
DOI https://dx.doi.org/10.2174/157488610789869166 |
Print ISSN 1574-8863 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3911 |
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