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- Title
K+ channel structure-activity relationships and mechanisms of drug-induced QT prolongation.
- Authors
Clancy, Colleen E; Kurokawa, Junko; Tateyama, Michihiro; Wehrens, Xander H T; Kass, Robert S
- 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.
- Publication
Annual review of pharmacology and toxicology, 2003, Vol 43, p441
- ISSN
0362-1642
- Publication type
Journal Article
- DOI
10.1146/annurev.pharmtox.43.100901.140245