Prokinetic Agents and QT Prolongation: A Familiar Scene with New Actors
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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ABSTRACT: Gastrointestinal (GI) dysfunction is a common but underestimated feature in Parkinson's disease (PD). Out of the multimodal spectrum of treatment options, there currently are only a few pharmacological treatments available to improve gastrointestinal motility and symptoms. Because enteric nervous function is mainly regulated by transmitters different from those involved in the brain, dopamine replacement is not a treatment option in PD patients. This article focuses on the known regulative mechanism of GI function and presents known and upcoming treatment options for GI dysfunction in PD.Journal of the neurological sciences 07/2011; 310(1-2):152-8. DOI:10.1016/j.jns.2011.06.050 · 2.47 Impact Factor
- PLoS ONE 08/2013; 8(9). DOI:10.1371/annotation/8824e161-bf8f-4f78-81e0-a62a1540276d · 3.23 Impact Factor
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ABSTRACT: To date, few animal experiments have been conducted to examine the effects and mechanisms of buspirone in inducing the relaxation of the gastric fundus. The aim of this study is to examine the effects and mechanisms of buspirone, 5-HT1a receptor agonist, in the accommodation of gastric fundus muscle in an animal experimental model using guinea pigs. In the current study, we performed an immunohistochemistry for 5-HT1a receptors in the tissue samples collected from the stomach of guinea pig, an ex vivo experiment to examine the electrical field stimulation (EFS)-induced relaxation of the circular muscle in the gastric fundus in guinea pigs and an in vivo experiment to measure the intragastric pressure through the insertion of the balloon catheter in the fundus. Immunohistochemical stains for 5-HT1a receptor could confirm the expression of 5-HT1a receptor in guinea pig stomach. There was a significant dose-dependent inhibition of the EFS-induced relaxation of fundic muscle strips following the treatment with WAY-100635 (5-HT1a antagonist), but this was significantly improved following the treatment with buspirone. An in vivo measurement of the gastric fundic tone showed that there was a significant decrease in the intragastric pressure at same volume by pretreatment with buspirone as compared with the vehicle control, but this could be prevented with the treatment with WAY-100635. Based on our results, it can be concluded that buspirone is effective in relaxing the gastric fundus via 5-HT1a receptor pathway in both in vitro and in vivo experimental models using guinea pigs. © 2015 John Wiley & Sons Ltd.Neurogastroenterology and Motility 02/2015; 27(4). DOI:10.1111/nmo.12523 · 3.59 Impact Factor