Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
Departments of Cardiovascular Medicine, Pediatrics, and Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Neurogastroenterol Motil. 2018 Jun;30(6):e13302. doi: 10.1111/nmo.13302. Epub 2018 Feb 14.
Gastrointestinal sensorimotor dysfunction underlies a wide range of esophageal, gastric, and intestinal motility and functional disorders that collectively constitute nearly half of all referrals to gastroenterologists. As a result, substantial effort has been dedicated toward the development of prokinetic agents intended to augment or restore normal gastrointestinal motility. However, the use of several clinically efficacious gastroprokinetic agents, such as cisapride, domperidone, erythromycin, and tegaserod, is associated with unfavorable cardiovascular safety profiles, leading to restrictions in their use.
The purpose of this review is to detail the cellular and molecular mechanisms that lead commonly to drug-induced cardiac arrhythmias, specifically drug-induced long QT syndrome, torsades de pointes, and ventricular fibrillation, to examine the cardiovascular safety profiles of several classes of prokinetic agents currently in clinical use, and to explore potential strategies by which the risk of drug-induced cardiac arrhythmia associated with prokinetic agents and other QT interval prolonging medications can be mitigated successfully.
胃肠道感觉运动功能障碍是引起食管、胃和肠道动力及功能障碍的基础，这些障碍共同构成了近一半的胃肠病学家就诊的原因。因此，人们致力于开发促动力药物，旨在增强或恢复正常的胃肠道动力。然而，几种临床有效的胃肠促动力药物的使用，如西沙必利、多潘立酮、红霉素和替加色罗，与不利的心血管安全性相关，导致其使用受限。
本综述的目的是详细描述导致药物引起的心律失常（特别是药物引起的长 QT 综合征、尖端扭转型室性心动过速和心室颤动）的常见细胞和分子机制，检查目前临床使用的几类促动力药物的心血管安全性，并探讨成功减轻促动力药物和其他 QT 间期延长药物相关药物引起的心律失常风险的潜在策略。
