NDLI: Drug- and non-drug-associated QT interval prolongation

Content Provider	PubMed Central
Author	Van Noord, Charlotte Mark, Eijgelsheim Stricker, Bruno H. Ch
Abstract	Sudden cardiac death is among the most common causes of cardiovascular death in developed countries. The majority of sudden cardiac deaths are caused by acute ventricular arrhythmia following repolarization disturbances. An important risk factor for repolarization disturbances is use of QT prolonging drugs, probably partly explained by gene–drug interactions. In this review, we will summarize QT interval physiology, known risk factors for QT prolongation, including drugs and the contribution of pharmacogenetics. The long QT syndrome can be congenital or acquired. The congenital long QT syndrome is caused by mutations in ion channel subunits or regulatory protein coding genes and is a rare monogenic disorder with a mendelian pattern of inheritance. Apart from that, several common genetic variants that are associated with QT interval duration have been identified. Acquired QT prolongation is more prevalent than the congenital form. Several risk factors have been identified with use of QT prolonging drugs as the most frequent cause. Most drugs that prolong the QT interval act by blocking hERG-encoded potassium channels, although some drugs mainly modify sodium channels. Both pharmacodynamic as well as pharmacokinetic mechanisms may be responsible for QT prolongation. Pharmacokinetic interactions often involve drugs that are metabolized by cytochrome P450 enzymes. Pharmacodynamic gene–drug interactions are due to genetic variants that potentiate the QT prolonging effect of drugs. QT prolongation, often due to use of QT prolonging drugs, is a major public health issue. Recently, common genetic variants associated with QT prolongation have been identified. Few pharmacogenetic studies have been performed to establish the genetic background of acquired QT prolongation but additional studies in this newly developing field are warranted.
Related Links	http://dx.doi.org/10.1111/j.1365-2125.2010.03660.x
Ending Page	23
Page Count	8
Starting Page	16
File Format	PDF
ISSN	03065251
e-ISSN	13652125
Journal	British Journal of Clinical Pharmacology
Issue Number	1
Volume Number	70
Language	English
Publisher	Blackwell Science Inc
Publisher Date	2010-03-01
Access Restriction	Open
Rights Holder	Blackwell Science Inc
Subject Keyword	Pharmacology (medical) Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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