Review article: cardiac adverse effects of gastrointestinal prokinetics

Abstract

Gastrointestinal prokinetics, such as metoclopramide, cisapride and levosulpiride, are widely used for the management of functional gut disorders. Recently, several studies have shown that cisapride (a partial 5-HT4 receptor agonist) can induce dose-dependent cardiac adverse effects, including lengthening of the electrocardiographic QT interval, syncopal episodes and ventricular dysrhythmias. Until recently, it was not clear whether these effects were dependent on 5-HT4 receptor activation or related to peculiar characteristics in the molecular structure of single agents within the benzamide class. Experimental evidence now favours the second hypothesis: cisapride possesses Class III antiarrhythmic properties and prolongs the action potential duration through blockade of distinct voltage-dependent K+ channels, thus delaying cardiac repolarization and prolonging the QT interval. Patients at risk of cardiac adverse effects are children, subjects with idiopathic, congenital or acquired long QT syndrome and, in particular, those receiving concomitant medication with Class III antiarrhythmic agents, some H1-receptor antagonists (e.g. terfenadine), or drugs such as azole antifungals (e.g. ketoconazole, itraconazole, miconazole and fluconazole) and macrolide antibacterials (e.g. erythromycin, clarithrod-mycin and troleandomycin), which can inhibit cisapride metabolism by interfering with the CYP3A4 isoenzyme.

Electrophysiological effects of 5‐hydroxytryptamine on isolated human atrial myocytes, and the influence of chronic β‐adrenoceptor blockade

“…It has been postulated that 5-HT is involved in the progression of atrial fibrillation (AF) in patients due to its release from aggregating platelets within the fibrillating atria (Kaumann, 1994). In addition, there has been concern about the potential for atrial arrhythmia generation when using 5-HT 4 receptor agonists as gastrokinetic agents (Medhurst & Kaumann, 1993;Tonini et al, 1999). In human atrial isolated muscle, arrhythmic contractions were induced by 5-HT, and abolished by a selective 5-HT 4 receptor antagonist (Kaumann & Sanders, 1994).…”

Refluxo gastroesofágico em cães anestesiados: fisiopatologia, clínica, diagnóstico e terapêutica

“…O bloqueio desses receptores inibitórios por fármacos antagonistas resulta no efeito procinético (TONINI et al, 1999;PASRICHA, 2006). Alguns fármacos antidopaminérgicos interagem com os receptores serotoninérgicos, contribuindo para o efeito procinético (TONINI et al, 1999).…”

“…O bloqueio desses receptores inibitórios por fármacos antagonistas resulta no efeito procinético (TONINI et al, 1999;PASRICHA, 2006). Alguns fármacos antidopaminérgicos interagem com os receptores serotoninérgicos, contribuindo para o efeito procinético (TONINI et al, 1999). A serotonina desencadeia o reflexo peristáltico por estimular os neurônios sensoriais intrínsecos do plexo mioentérico (via receptor 5-HT4), bem como dos neurônios sensoriais vagais e espinhais extrínsecos (via receptor 5-HT3).…”

Pharmacological therapy of feed intolerance in the critically ills

“…Although the regular use of nasogastric naloxone (an opioid antagonist) has been shown 150 August 6, 2014|Volume 5|Issue 3| WJGPT|www.wjgnet.com prolongation of the QT interval, torsades de pointes, has always been a major concern with the use of currently available prokinetics [56] , as all agents have been shown to block the human ether-a-go-go-related gene currents which is important in mediation of cardiac rhythm [57,58] . Compared to metoclopramide and erythromycin, cisapride and domperidone are approximately 100 times more potent in the inhibition of human ether-a-go-gorelated gene currents and, thus, carry the highest risk of inducing cardiac arrthymia [57,58] .…”