K+ Channel Structure-Activity Relationships and Mechanisms of Drug-Induced QT Prolongation

Colleen E Clancy, Junko Kurokawa, Michihiro Tateyama, Xander H T Wehrens, Robert S. Kass

Research output: Contribution to journalArticle

74 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)441-461
Number of pages21
JournalAnnual Review of Pharmacology and Toxicology
Volume43
DOIs
StatePublished - 2003
Externally publishedYes

Fingerprint

Structure-Activity Relationship
Physiological Effects of Drugs
Pharmacology
Physiology
Polymorphism
Electrocardiography
Pharmaceutical Preparations
Psychotic Disorders
Cardiac Arrhythmias
Heart Diseases
Hypersensitivity
Defects
Substrates
Therapeutics

Keywords

  • Abnormal repolarization
  • Arrhythmia
  • I
  • I
  • K channel block

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

K+ Channel Structure-Activity Relationships and Mechanisms of Drug-Induced QT Prolongation. / Clancy, Colleen E; Kurokawa, Junko; Tateyama, Michihiro; Wehrens, Xander H T; Kass, Robert S.

In: Annual Review of Pharmacology and Toxicology, Vol. 43, 2003, p. 441-461.

Research output: Contribution to journalArticle

Clancy, Colleen E ; Kurokawa, Junko ; Tateyama, Michihiro ; Wehrens, Xander H T ; Kass, Robert S. / K+ Channel Structure-Activity Relationships and Mechanisms of Drug-Induced QT Prolongation. In: Annual Review of Pharmacology and Toxicology. 2003 ; Vol. 43. pp. 441-461.
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