We have located links that may give you full text access.
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Severe Proarrhythmic Potential of the Antiemetic Agents Ondansetron and Domperidone.
Cardiovascular Toxicology 2017 October
The potential of ondansetron and domperidone, both clinically established antiemetic agents, to increase the QT-interval has been described in several case reports. Therefore, the aim of the present study was to investigate whether these drugs may provoke polymorphic ventricular tachycardia in a sensitive experimental model of drug-induced proarrhythmia. In 10 female rabbits, ondansetron (1, 5 and 10 µM, n = 10) or domperidone (0.5, 1 and 2 µM, n = 8) was infused after obtaining baseline data. Eight endo- and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG reproduced the clinically observed QT-prolongation (ondansetron: 1 µM:+17 ms, 5 µM:+41 ms, 10 µM:+78 ms, p < 0.01; domperidone: 0.5 µM:+57 ms, 1 µM:+79 ms, 2 µM:+99 ms, p < 0.01). This was accompanied by a significant increase in action potential duration at 90% of repolarization. Administration of both agents also increased dispersion of repolarization (ondansetron: 1 µM:+12 ms, 5 µM:+17 ms; 10 µM:+18 ms, p < 0.05; domperidone: 0.5 µM:+19 ms, 1 µM:+27 ms; 2 µM:+23 ms p < 0.05). Lowering of potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EADs) in 9 of 10 ondansetron-treated hearts and induced polymorphic ventricular tachycardia (VT) resembling torsade de pointes in 7 of 10 ondansetron-treated hearts (86 episodes). Under the influence of domperidone, EAD and polymorphic VT occurred in 7 of 8 hearts (131 episodes). In the present study, both ondansetron and domperidone demonstrated a severe proarrhythmic potential. A significant prolongation of cardiac repolarization as well as a marked increase in spatial dispersion of repolarization represents the underlying electrophysiologic mechanisms. These results imply that application of ondansetron should be handled carefully. For regular administration, ECG monitoring should be mandatory.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app