A case of prenylamine toxicity showing the torsade de pointes phenomenon in sinus rhythm?

Meanock, C. I.; Noble, M. I. M.

doi:10.1136/pgmj.57.668.381

Cited by 13 publications

(7 citation statements)

References 4 publications

(2 reference statements)

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“…In the subsequent decades, attention was consequently directed to routine measurement of the QT interval in patients receiving cardiac antiarrhythmic drugs such as procainamide, quinidine and disopyramide but routine surveillance for other classes of medicines was not performed as there was no known link between those agents and QT prolongation or TdP. The landscape changed in 1988, when prenylamine (Segontin) [7], a calcium channel blocking analogue of amphetamine used in the treatment of angina pectoris, was the first drug to be withdrawn from the market due to sudden death associated with QT prolongation. Several years later a case report of TdP and QT lengthening with the antihistamine terfenadine (Seldane) was published and this drug was eventually removed from the market in 1997 [8].…”

Section: History Of the Qt Interval And Its Importance In Early Drmentioning

confidence: 99%

QT Assessment in Early Drug Development: The Long and the Short of It

Lester

Paglialunga

Johnson

2019

IJMS

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The QT interval occupies a pivotal role in drug development as a surface biomarker of ventricular repolarization. The electrophysiologic substrate for QT prolongation coupled with reports of non-cardiac drugs producing lethal arrhythmias captured worldwide attention from government regulators eventuating in a series of guidance documents that require virtually all new chemical compounds to undergo rigorous preclinical and clinical testing to profile their QT liability. While prolongation or shortening of the QT interval may herald the appearance of serious cardiac arrhythmias, the positive predictive value of an abnormal QT measurement for these arrhythmias is modest, especially in the absence of confounding clinical features or a congenital predisposition that increases the risk of syncope and sudden death. Consequently, there has been a paradigm shift to assess a compound’s cardiac risk of arrhythmias centered on a mechanistic approach to arrhythmogenesis rather than focusing solely on the QT interval. This entails both robust preclinical and clinical assays along with the emergence of concentration QT modeling as a primary analysis tool to determine whether delayed ventricular repolarization is present. The purpose of this review is to provide a comprehensive understanding of the QT interval and highlight its central role in early drug development.

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Section: History Of the Qt Interval And Its Importance In Early Drmentioning

confidence: 99%

QT Assessment in Early Drug Development: The Long and the Short of It

Lester

Paglialunga

Johnson

2019

IJMS

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“…Proarrhythmia is most common in the first week after increasing the dose [198], and during hypokalemia [180] and sinus bradycardia. After withdrawal, the QT interval rarely [198] normalized within 24 hours [145,180]. Proarrhythmic events were best treated by isoprenaline [198], isopropyl-noradrenaline [181], or by pacing, but not by lidocaine [73,180].…”

Section: Characteristics Of Proarrhythmia After Drug-lnduced Qt Prolomentioning

confidence: 99%

QT-Interval prolonging drugs: Mechanisms and clinical relevance of their arrhythmogenic hazards

Zehender

Hohnloser

Just

1991

Cardiovasc Drug Ther

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The antiarrhythmic principle of drug-induced QT-interval prolongation is well known. However, with the widespread use of the presently known and new Class III antiarrhythmic agents under investigation, and the growing number of agents not primarily designed as antiarrhythmic drugs that potentially cause QT prolongation, we have also become aware of the proarrhythmic hazards associated with many of these agents. The proarrhythmic risk differs markedly from one agent to another and interferes with many individual clinical variables (e.g., hypokalemia, sinus bradycardia). This paper summarizes the present data on the proarrhythmic risk of drug-induced QT prolongation, including the value and problems of the rate-corrected QT interval, the mechanisms involved in the genesis of proarrhythmia, and the clinical cofactors that facilitate the occurrence of proarrhythmic events. In addition, an extensive database provides information on the known proarrhythmic risk of all currently used QT-prolonging agents.

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“…However, prolongation may be extreme in individual patients and this may be associated with dangerous ventricular arrhythmias (Bens et al, 1973;Krikler & Curry, 1976;Puritz et al, 1977;Riccioni et al, 1980;Freestone et al, 1981;Meanock & Noble, 1981;Grenadier et al, 1982;Tamari et al, 1982). In this patient the markedly prolonged QT, on admission can be attributed to prenylamine because it was not present before the drug was started, it returned to normal after prenylamine was stopped, and the patient was not taking any other drug known to prolong the QTc.…”

Section: Discussionmentioning

confidence: 86%

“…Extreme prolongation of the QTc predisposes to serious ventricular arrhythmias and there have been several reports of ventricular tachycardia associated with prenylamine treatment (Bens et al, 1973;Krikler & Curry, 1976;Puritz et al, 1977;Riccioni et al, 1980;Freestone et al, 1981;Meanock & Noble, 1981;Grenadier et al, 1982;Tamari et al, 1982). This tachycardia often has the peculiar configuration termed torsade de pointes.…”

Section: Introductionmentioning

confidence: 99%