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 language | English (US) |
|---|---|
| Pages (from-to) | 441-461 |
| Number of pages | 21 |
| Journal | Annual Review of Pharmacology and Toxicology |
| Volume | 43 |
| DOIs | |
| State | Published - 2003 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - K+ Channel Structure-Activity Relationships and Mechanisms of Drug-Induced QT Prolongation
AU - Clancy, Colleen E
AU - Kurokawa, Junko
AU - Tateyama, Michihiro
AU - Wehrens, Xander H T
AU - Kass, Robert S.
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
KW - Abnormal repolarization
KW - Arrhythmia
KW - I
KW - I
KW - K channel block
UR - http://www.scopus.com/inward/record.url?scp=0042780275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042780275&partnerID=8YFLogxK
U2 - 10.1146/annurev.pharmtox.43.100901.140245
DO - 10.1146/annurev.pharmtox.43.100901.140245
M3 - Article
C2 - 12540747
AN - SCOPUS:0042780275
VL - 43
SP - 441
EP - 461
JO - Annual Review of Pharmacology and Toxicology
JF - Annual Review of Pharmacology and Toxicology
SN - 0362-1642
ER -