期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 108, 期 4, 页码 462-471出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.08178FP
关键词
hydroxyzine; QT prolongation; human ether-a-go-go-related gene (HERG); potassium channel; torsade de pointes
资金
- Ministry of Education, Culture, Sports, Science, and Technology
- Ministry of Health, Labour, and Welfare, Japan
QT prolongation, a risk factor for arrhythmias, can result from genetic variants in one (or more) of the genes governing cardiac repolarization as well as intake of drugs known to affect a cardiac K+ channel encoded by human ether-a-go-go-related gene (HERG). In this paper, we will report a case of drug-induced long QT syndrome associated with an HI-receptor antagonist, hydroxyzine, in which a mutation was identified in the HERG gene. After taking 75 mg of hydroxyzine for several days, a 34-year-old female began to experience repetitive syncope. The deleterious effect of hydroxyzine was suspected because QTc interval shortened from 630 to 464 ms after cessation of the drug. Later on, the patient was found to harbor an A614V-HERG mutation. By using the patch-clamp technique in the heterologous expression system, we examined the functional outcome of the A614V mutation and confirmed a dominant-negative effect on HERG expression. Hydroxyzine concentration-dependently inhibited both wild-type (WT) and WT/A614V-HERG K+ currents. Half-maximum block concentrations of WT and WT/A614V-HERG K+ currents were 0.62 and 0.52 mu M, respectively. Thus, accidental combination of genetic mutation and intake of hydroxyzine appeared to have led to a severe phenotype, probably, syncope due to torsade de pointes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据