TY - JOUR
T1 - Cardiovascular safety of prokinetic agents
T2 - A focus on drug-induced arrhythmias
AU - Giudicessi, J. R.
AU - Ackerman, M. J.
AU - Camilleri, M.
N1 - Publisher Copyright:
© 2018 John Wiley & Sons Ltd
PY - 2018/6
Y1 - 2018/6
N2 - Background: 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. Purpose: 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.
AB - Background: 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. Purpose: 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.
KW - 5-HT
KW - adverse drug reactions
KW - cytochrome P450
KW - drug-induced long QT syndrome
KW - gastrointestinal motility
KW - torsades de pointes
UR - http://www.scopus.com/inward/record.url?scp=85047856104&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047856104&partnerID=8YFLogxK
U2 - 10.1111/nmo.13302
DO - 10.1111/nmo.13302
M3 - Review article
C2 - 29441683
AN - SCOPUS:85047856104
SN - 1350-1925
VL - 30
JO - Neurogastroenterology and Motility
JF - Neurogastroenterology and Motility
IS - 6
M1 - e13302
ER -