K+ Channel Structure-Activity Relationships and Mechanisms of Drug-Induced QT Prolongation
- 1 April 2003
- journal article
- review article
- Published by Annual Reviews in Annual Review of Pharmacology and Toxicology
- Vol. 43 (1) , 441-461
- https://doi.org/10.1146/annurev.pharmtox.43.100901.140245
Abstract
Pharmacological intervention, often for the purpose of treating syndromes unrelated to cardiac disease, can increase the vulnerability of some patients to life-threatening rhythm disturbances. This may be due to an underlying propensity stemming from genetic defects or polymorphisms, or structural abnormalities that provide a substrate allowing for the initiation of arrhythmic triggers. A number of pharmacological agents that have proven useful in the treatment of allergic reactions, gastrointestinal disorders, and psychotic disorders, among others, have been shown to reduce repolarizing K+ currents and prolong the QT interval on the electrocardiogram. Understanding the structural determinants of K+ channel blockade may provide new insights into the mechanism and rate-dependent effects of drugs on cellular physiology. Drug-induced disruption of cellular repolarization underlies electrocardiographic abnormalities that are diagnostic indicators of arrhythmia susceptibility.Keywords
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