The Association Between Intravenous Haloperidol and Torsades de Pointes

Hunt, Noel; Stern, Theodore A.

doi:10.1016/s0033-3182(95)71609-7

Cited by 113 publications

(49 citation statements)

References 46 publications

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“…Pimozide, sultopiride and droperidole also prolong QTc interval and have been associated with TdP and sudden death, but far fewer data are available [ 121,130 ]. The high-potency drug haloperidole can prolong QTc interval, causes TdP and sudden death at normal therapeutic doses [ 131 ], but the frequency by which these effects occur is less than with thioridazine [ 128 ]. Similar cardiovascular risks of traditional antipsychotics used at therapeutic dosage were published in the USA in a retrospective study investigating 481,744 persons (aged 15-84 years, from 1988 to 1993) [ 132 ].…”

Section: Clinical Evidencementioning

confidence: 99%

Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns?

Pacher¹,

Kecskeméti

2004

CPD

346

218

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The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na + , Ca 2+ and K + channels often leading to life-threatening arrhythmia.To overcome the toxicity of old generation of antidepressants and antipsychotics, selective serotonin reuptake inhibitor antidepressants (SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxin) and several new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) were introduced during the past decade. Although these new compounds are not more effective in treating psychiatric disorders than older medications, they gained incredible popularity since they have been reported to have fewer and more benign side effect profile (including cardiovascular) than predecessors.Surprisingly, an increasing number of case reports have demonstrated that the use of SSRIs and new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) is associated with cases of arrhythmias, prolonged QTc interval on electrocardiogram (ECG) and orthostatic hypotension in patients lacking cardiovascular disorders, raising new concerns about the putative cardiovascular safety of these compounds. In agreement with these clinical reports these new compounds indeed show marked cardiovascular depressant effects in different mammalian and human cardiovascular preparations by inhibiting cardiac and vascular Na + , Ca 2+ and K + channels. Taken together, these results suggest that the new generation of antidepressants and antipsychotics also have clinically important cardiac as well as vascular effects. Clinicians should be more vigilant about these potential adverse reactions and ECG control may be suggested during therapy, especially in patients with cardiovascular disorders.The primary goal of this review is to shed light on the recently observed clinically important cardiovascular effects of new antidepressants and antipsychotics and discuss the mechanism beyond this phenomenon.

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Section: Clinical Evidencementioning

confidence: 99%

Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns?

Pacher¹,

Kecskeméti

2004

CPD

346

218

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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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“…3,4 Wilt et al observed this type of arrhythmia in four women who received large doses of intravenous haloperidol. 5 In Kay's series of 32 patients and Di Salva's, torsades de pointes occurred mostly in patients with underlying heart disease, 6,7 most frequently ischemic heart disease, in 53% of patients in some series 6 but it is also described in patients with liver diseases 8,9 and in critically ill patients. 10 It has also been described with doses as small as 4 mg. 11 In more than 90% of patients, the initiating event is a premature ventricular beat occurring following an R on T phenomenon as observed in this report.…”

Section: Discussionmentioning

confidence: 98%

Torsades de pointes secondary to intravenous haloperidol after coronary bypass grafting surgery

Perrault

Denault

Carrier

et al. 2000

Can J Anesth/J Can Anesth

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The Association Between Intravenous Haloperidol and Torsades de Pointes

Cited by 113 publications

References 46 publications

Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns?

Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns?

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

Torsades de pointes secondary to intravenous haloperidol after coronary bypass grafting surgery

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