Iatrogenic torsade de pointes induced by thioridazine

Kiriike, Nobuo; Maeda, Yoshinori; Nishiwaki, Shushi; Izumiya, Yasuhiro; Katahara, S.; Mui, Koji; Kawakita, Yukio; Nishikimi, Takahiro; Takeuchi, Kazuhide; Takeda, Tadanao

doi:10.1016/0006-3223(87)90135-1

Cited by 31 publications

(11 citation statements)

References 9 publications

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“…227 Numerous cases of electrocardiographic changes and ventricular arrhythmias with thioridazine have been reported. [228][229][230][231][232][233][234][235][236][237][238][239] This adverse reaction has been reported with both standard dosing as well as in overdose situations. A recent epidemiologic study 121 found that in patients taking psychotropic therapy, those receiving thioridazine were at higher risk for QTc interval lengthening compared with other phenothiazines (only droperidol put patients at higher risk).…”

Section: Definite Associationmentioning

confidence: 99%

Clinical Relevance and Management of Drug‐Related QT Interval Prolongation

2003

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Much attention recently has focused on drugs that prolong the QT interval, potentially leading to fatal cardiac dysrhythmias (e.g., torsade de pointes). We provide a detailed review of the published evidence that supports or does not support an association between drugs and their risk of QT prolongation. The mechanism of drug-induced QT prolongation is reviewed briefly, followed by an extensive evaluation of drugs associated with QT prolongation, torsade de pointes, or both. Drugs associated with QT prolongation are identified as having definite, probable, or proposed associations. The role of the clinician in the prevention and management of QT prolongation, drug-drug interactions that may occur with agents known to affect the QT interval, and the impact of this adverse effect on the regulatory process are addressed.

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Section: Definite Associationmentioning

confidence: 99%

Clinical Relevance and Management of Drug‐Related QT Interval Prolongation

2003

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“…However, clinical studies have shown that sertindole, as well as the other members of this group of drugs (e.g., risperidone, ziprazodine, haloperidol, olanzapine, and clozapine) may affect cardiac repolarization, i.e., induce prolongation of the QT interval (van Kammen et al, 1996). Although extremely rare, in individual patients proarrhythmia of the TdP type resulting from abnormal drug-induced prolongation of myocardial repolarization has been reported for antipsychotics (Kiriike et al, 1987;Hunt and Stern, 1995;Krahenbuhl et al, 1995;Jackson et al, 1997).…”

Section: Eckardt Et Almentioning

confidence: 99%

Electrophysiologic Characterization of the Antipsychotic Drug Sertindole in a Rabbit Heart Model of Torsade de Pointes: Low Torsadogenic Potential Despite QT Prolongation

Eckardt

Breithardt²,

Haverkamp³

2002

J Pharmacol Exp Ther

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There is growing concern that antipsychotic drugs that prolong the QT interval almost always increase the risk for patients to develop life-threatening ventricular tachyarrhythmias (VTs) of the torsade de pointes type. We therefore sought to compare the electrophysiologic effects of the psychotropic agent sertindole, which prolongs cardiac repolarization by inhibiting the rapid component of the delayed rectifier potassium current (I Kr ) but has a low torsadogenic potential to the antiarrhythmic agent dl-sotalol. In 18 Langendorff-perfused rabbit hearts, sotalol (10 M, n ϭ 8) and sertindole (0.5, 1.0, and 1.5 M; n ϭ 10) led to significant and comparable QT prolongation. In the presence of sotalol, torsade de pointes reproducibly occurred in atrioventricular node-blocked hearts after lowering the potassium concentration to 1.5 mM. High doses of sertindole (1.5 M) only caused monomorphic VT (n ϭ 4) and nonsustained polymorphic VT (n ϭ 2) in the presence of QRS prolongation. Multiple simultaneous epi-and endocardial monophasic action potentials and a volume-conducted ECG demonstrated widening of the T/U wave, early afterdepolarizations, and increased dispersion of repolarization in the presence of dlsotalol. In contrast to sotalol, QT and monophasic action potential prolongation were cycle length-independent in the presence of sertindole. Sertindole had no significant effect on transmural or interventricular dispersion of repolarization. Early afterdepolarizations did not occur. Despite comparable QT prolongation, sertindole did not display the proarrhythmic profile typical of other blockers of I Kr such as dl-sotalol. It is likely that a different mode of interaction between sertindole and the channel and/or additional pharmacological effects of sertindole, e.g., its ability to inhibit I Na and/or its ability to block ␣ 1 -receptors, play a role.

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“…3 Nonspecific ECG abnormalities that reflect abnormal cardiac repolarization are common in psychiatric patients who are receiving phenothiazines,4-8 but the effects of neuroleptic drugs on the QT interval and QT dispersion have not been studied in any detail. The antipsychotic drug most commonly implicated in causing arrhythmia and sudden death is thioridazine, [9][10][11][12][13][14][15][16][17][18] an alkylpiperadine phenothiazine derivative. This agent has quinidine-like electrophysiologic effects, slowing fast sodium entry and his-Purkinje cardiac conduction and prolonging ventricular repolarization.…”

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confidence: 99%