Torsade de pointes with an antihistamine metabolite: Potassium channel blockade with desmethylastemizole

Vicken R. Vorperian, Zhengfeng Zhou, Saeed Mohammad, Timothy J. Hoon, Christian Studenik, Craig T. January

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Objectives. Proarrhythmic effects have been observed with the selective histamine1 (H1) receptor antagonist drug astemizole, a widely prescribed antihistamine. The metabolites of astemizole and those of other antihistamine compounds have not been implicated as causative agents of cardiac arrhythmias. The purpose of this study was to examine whether desmethylastemizole, the principal metabolite of astemizole, blocks delayed rectifier potassium (K+) channels. Background. QT interval prolongation and torsade de pointes are associated with astemizole intake and have heen ascribed to block the repolarizing K+ currents, specifically the rapidly activating component of the delayed rectifier iKr. Astemizole undergoes extensive first-pass metabolism, and its dominant metabolite, desmethylastemizole, has a markedly prolonged elimination time. We report the clinical observation of QT prolongation and torsade de pointes in a patient with undetectahle serum concentrations of astemizole (+ current iKr with high affinity. The clinical observation of QT prolongation and torsade de pointes found with astemizole intake may principally be caused by the proarrhythmic effects of its metabolite desmethylastemizole.

Original languageEnglish (US)
Pages (from-to)1556-1561
Number of pages6
JournalJournal of the American College of Cardiology
Volume28
Issue number6
DOIs
StatePublished - Nov 15 1996
Externally publishedYes

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Astemizole
Torsades de Pointes
Histamine Antagonists
Potassium Channels
Delayed Rectifier Potassium Channels
Observation
Drug Receptors
desmethylastemizole
Cardiac Arrhythmias

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Torsade de pointes with an antihistamine metabolite : Potassium channel blockade with desmethylastemizole. / Vorperian, Vicken R.; Zhou, Zhengfeng; Mohammad, Saeed; Hoon, Timothy J.; Studenik, Christian; January, Craig T.

In: Journal of the American College of Cardiology, Vol. 28, No. 6, 15.11.1996, p. 1556-1561.

Research output: Contribution to journalArticle

Vorperian, Vicken R. ; Zhou, Zhengfeng ; Mohammad, Saeed ; Hoon, Timothy J. ; Studenik, Christian ; January, Craig T. / Torsade de pointes with an antihistamine metabolite : Potassium channel blockade with desmethylastemizole. In: Journal of the American College of Cardiology. 1996 ; Vol. 28, No. 6. pp. 1556-1561.
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