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Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.
J Cardiovasc Pharmacol. 2003 Jun; 41(6):934-7.JC

Abstract

Cases of QT prolongation and sudden death have been reported with risperidone, a neuroleptic agent increasingly prescribed worldwide. Although hypokalemia was present in some of these events, we hypothesized that risperidone may have unsuspected electrophysiologic effects predisposing patients to proarrhythmia. In six isolated guinea pig hearts, risperidone elicited prolongation of cardiac repolarization: action potential duration increased from a baseline value of 128 ms +/- 5 to 147 ms +/- 5 (15%) with risperidone 1 microM during pacing at 250-ms cycle length, whereas the increase was only 10%, from 101 ms +/- 2 to 111 ms +/- 4, with pacing at a cycle length of 150 ms. In human ether-a-go-go (HERG)-transfected Chinese hamster ovary cells (n = 16), risperidone caused concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current with an IC(50) for tail block of 261 nM. Risperidone did not block I(Ks). Risperidone exerts cardiac electrophysiologic effects similar to those of Class III antiarrhythmic drugs. These effects are observed at clinically relevant concentrations. Because risperidone is metabolized primarily by CYP2D6, these actions likely enhance risk for risperidone-related QT prolongation and proarrhythmia in specific patient subsets (e.g., poor metabolizers and those taking interacting drugs).

Authors+Show Affiliations

Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12775973

Citation

Drolet, Benoit, et al. "Risperidone Prolongs Cardiac Repolarization By Blocking the Rapid Component of the Delayed Rectifier Potassium Current." Journal of Cardiovascular Pharmacology, vol. 41, no. 6, 2003, pp. 934-7.
Drolet B, Yang T, Daleau P, et al. Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current. J Cardiovasc Pharmacol. 2003;41(6):934-7.
Drolet, B., Yang, T., Daleau, P., Roden, D. M., & Turgeon, J. (2003). Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current. Journal of Cardiovascular Pharmacology, 41(6), 934-7.
Drolet B, et al. Risperidone Prolongs Cardiac Repolarization By Blocking the Rapid Component of the Delayed Rectifier Potassium Current. J Cardiovasc Pharmacol. 2003;41(6):934-7. PubMed PMID: 12775973.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current. AU - Drolet,Benoit, AU - Yang,Tao, AU - Daleau,Pascal, AU - Roden,Dan M, AU - Turgeon,Jacques, PY - 2003/5/31/pubmed PY - 2004/4/13/medline PY - 2003/5/31/entrez SP - 934 EP - 7 JF - Journal of cardiovascular pharmacology JO - J. Cardiovasc. Pharmacol. VL - 41 IS - 6 N2 - Cases of QT prolongation and sudden death have been reported with risperidone, a neuroleptic agent increasingly prescribed worldwide. Although hypokalemia was present in some of these events, we hypothesized that risperidone may have unsuspected electrophysiologic effects predisposing patients to proarrhythmia. In six isolated guinea pig hearts, risperidone elicited prolongation of cardiac repolarization: action potential duration increased from a baseline value of 128 ms +/- 5 to 147 ms +/- 5 (15%) with risperidone 1 microM during pacing at 250-ms cycle length, whereas the increase was only 10%, from 101 ms +/- 2 to 111 ms +/- 4, with pacing at a cycle length of 150 ms. In human ether-a-go-go (HERG)-transfected Chinese hamster ovary cells (n = 16), risperidone caused concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current with an IC(50) for tail block of 261 nM. Risperidone did not block I(Ks). Risperidone exerts cardiac electrophysiologic effects similar to those of Class III antiarrhythmic drugs. These effects are observed at clinically relevant concentrations. Because risperidone is metabolized primarily by CYP2D6, these actions likely enhance risk for risperidone-related QT prolongation and proarrhythmia in specific patient subsets (e.g., poor metabolizers and those taking interacting drugs). SN - 0160-2446 UR - https://www.unboundmedicine.com/medline/citation/12775973/Risperidone_prolongs_cardiac_repolarization_by_blocking_the_rapid_component_of_the_delayed_rectifier_potassium_current_ L2 - http://dx.doi.org/10.1097/00005344-200306000-00016 DB - PRIME DP - Unbound Medicine ER -