Abstract：
:Torsades de pointes ventricular tachycardia (VT) has been reported in patients taking the nonsedating antihistamine, terfenadine. We performed electrophysiologic studies of 14 isolated guinea pig hearts using the Langendorff technique to assess whether terfenadine exerted actions that could be responsible for inducing the arrhythmia. Twelve hearts were perfused with an oxygenated Tyrode's solution containing a 2-microM preparation of either racemic, R-, or S-terfenadine. QT interval (QT), monophasic action potential duration (APD), and ventricular effective refractory periods (ERP) were measured at a fixed range of cycle lengths (CL). At 400-ms CL, both isomers and racemate prolonged QT and APD by 8% and ERP was increased by 14%. Infusion of vehicle, dimethyl sulfoxide (DMSO), alone in two hearts caused a slight decrease in QT and APD, suggesting that the direct effect of terfenadine on QT may have been underestimated. One-way analysis of variance (ANOVA) showed no statistical difference in effect on QT, APD, or ERP for the three forms of terfenadine (p < 0.05). These results support the conclusion that terfenadine induces torsades de pointes because of direct actions in delaying cardiac repolarization. The lack of stereospecificity in this action indicates that chirally pure formulations are not likely to have greater safety than the racemate.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Pinney SP,Koller BS,Franz MR,Woosley RLdoi
10.1097/00005344-199501000-00006subject
Has Abstractpub_date
1995-01-01 00:00:00pages
30-4issue
1eissn
0160-2446issn
1533-4023journal_volume
25pub_type
杂志文章abstract：:Diabetes mellitus is associated with significant morbidity and mortality caused by the micro- and macro-vascular complications that all too frequently develop during the lifetime of the diabetic patient. In attempts to treat the complications of diabetes, several different treatment strategies have been investigated. ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1991-01-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
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journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
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更新日期：1990-01-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199701000-00008
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199010000-00010
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/01.fjc.0000242059.89430.ac
更新日期：2006-08-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199500252-00019
更新日期：1995-01-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e3181953e0f
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199012000-00015
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0000000000000794
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e3181b04ce3
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journal_title：Journal of cardiovascular pharmacology
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
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更新日期：2015-12-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199508000-00021
更新日期：1995-08-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
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journal_title：Journal of cardiovascular pharmacology
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journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1990-01-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199801000-00001
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journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章
doi：10.1097/00005344-199424050-00007
更新日期：1994-11-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1982-01-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-01-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
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更新日期：1998-01-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
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更新日期：2003-05-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
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abstract：:Human saphenous veins were obtained at operation and assayed immediately (n = 10). The veins were cut into rings, suspended in organ chambers, and connected to force transducers for recording of isometric tension. One ring served as control; others were treated with either the alpha 1-adrenoceptor antagonist prazosin ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
