Life-Threatening Ventricular Arrhythmia (Torsades de Pointes) after Haloperidol Overdose

Henderson, R. A.; Lane, S. J.; Henry, JA

doi:10.1177/096032719101000110

Cited by 59 publications

(18 citation statements)

References 15 publications

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“…High dosage (either caused by metabolic drug-drug interactions 9 or overdosing) 18 may be a risk factor for drug-induced arrhythmias. Futhermore, the duration of use may influence the risk of drug-induced arrhythmias.…”

Section: Methodsmentioning

confidence: 99%

QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

Bruin

Hoes

Leufkens

2003

The American Journal of Cardiology

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Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice, and subsequently focused on several specific groups of patients who could be extremely vulnerable for drug-induced arrhythmias. We performed a case-control study in which patients (cases), hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998, were compared with their matched controls regarding current use of QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate conditional logistic regression, adjusting for potential confounding factors. Data were obtained from the PHARMO record linkage system. We identified 501 cases, 39 of whom used QTcprolonging drugs. A statistically nonsignificant increased risk for arrhythmias (OR 1.2, 95% CI 0.8 to 1.9) was observed in patients who received QTc-prolonging drugs. A clearly increased risk of arrhythmias was, however, found in patients with a history of asthma (OR 9.9, 95% CI 1.0 to 100) and in patients using potassiumlowering drugs (OR 5.3, 95% CI 1.1 to. 25.9). Our data do not suggest that there is a strong overall association between the use of QTc-prolonging drugs and hospitalization for cardiac arrhythmias in the population at large. However, there appears to be clinically relevant associations of patients with a history of asthma and patients taking potassium-lowering drugs. The use of QTc-prolonging drugs should therefore be either avoided or monitored closely in these specific patients. ᮊ2003 by Excerpta Medica, Inc.(Am J Cardiol 2003;91:59 -62) C ardiac arrhythmias as an adverse effect of noncardiac drugs has been an issue of growing importance in medical science during the last few years, resulting in regulatory action concerning several drugs. 1 Because of the seriousness of this adverse effect, regulatory action has sometimes already been taken after a few case reports, before the actual risk has been quantified in large population-based studies.For only a few of all QTc-prolonging drugs, studies have unequivocally shown a causal relation between the use of the drugs and the occurrence of cardiac arrhythmias. The use of antihistamines has been associated with an increased risk for cardiac arrhythmias. 2 In contrast, no increased risk for serious rhythm disorders was observed in patients who took cisapride, 3 although its use has been linked to the occurrence of cardiac arrhythmias in several case reports. 4,5 In this population-based study, we evaluated the risk for serious cardiac arrhythmias and the use of several noncardiac QTc-prolonging drugs in day-to-day practice. Subsequently, we focused on several specific groups of patients who may be quite vulnerable to druginduced arrhythmias.

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Section: Methodsmentioning

confidence: 99%

QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

Bruin

Hoes

Leufkens

2003

The American Journal of Cardiology

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“…TdP is characterized by a twisting morphology of the QRS complex around the isoelectric baseline and can occur in congenital and acquired form induced by various cardiac and non-cardiac drugs. Among antipsychotics haloperidol, droperidol, pimozide, sertindole, thioridazine were found to cause definitively TdP [112][113][114][115][116][117][118]. Several other antipsychotics including typical (chlorpromazine, fluphenazine, mesoridazine, prochlorperazine, trifluperazine, sultopride) [119][120][121] (quetiapine, olanzapine, risperidone, ziprasidone) [122][123][124][125][126][127] have been reported to prolong the corrected QT interval (corrected for heart rate)(QTc).…”

Section: Clinical Evidencementioning

confidence: 99%

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

Pacher¹,

Kecskeméti

2004

CPD

339

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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“…administration, and in overdose situations (Fayer 1986;Kriwisky et al 1990;Henderson et al 1991;Hunt & Stern 1995;Glassman & Bigger 2001). Among 223 patients receiving i.v.…”

Section: Butyrophenonesmentioning

confidence: 99%

Drug-induced block of cardiac HERG potassium channels and development oftorsade de pointesarrhythmias: the case of antipsychotics

Calderone

Testai

Martinotti

et al. 2005

Journal of Pharmacy and Pharmacology

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The prolongation of the cardiac repolarization process, a result of the blocking of the Human Ether-ago-go Related Gene potassium channel, is an undesired accessory property shared by many pharmacological classes of non-cardiovascular drugs. Often the delayed cardiac repolarization process can be identified by a prolongation of the QT interval of the electrocardiograph. In these conditions, premature action potentials can trigger a dangerous polymorphic ventricular tachyarrhythmia, known as torsade de pointes, which occasionally can result in lethal ventricular fibrillation. In this work, brief descriptions of the electrophysiological basis of torsade de pointes and of the several pharmacological classes of torsadogenic drugs are given. Attention is focused on antipsychotics, with a deeper overview on the experimental and clinical reports about their torsadogenic properties. The cardiac action potentialCardiac action potentials are generated by trans-membrane movements of ion species, flowing principally through specific channels. In a typical human cardiac action potential ( Figure 1A), five different phases can be recognized. Phase 0 is a rapid depolarization process resulting from a massive inward flow of Na þ (current I Na ). The following phase 1 is linked to the inactivation of the I Na current and to a weak and transient repolarization due to an outward flow of K þ (current I to ). Phase 2 reflects an almost iso-electric plateau generated by the simultaneous activation of a depolarizing inward Ca þþ current, a repolarizing outward rapidly activated K þ current (current I Kr ) and a repolarizing outward slowly activated K þ current (current I Ks ). Phase 3 reflects the complete membrane repolarization due to many K þ currents (mainly I Ks and I Kr ), which leads the cell to the recovery of resting membrane potential. Finally, phase 4 is the resting period, ensured by inward rectifier K þ currents (I K1 ), before a new following cardiac cycle. The QT intervalA typical electrocardiograph (ECG) tracing of a human cardiac cycle ( Figure 1B) starts with a P wave (80-110 ms) representing the atrial depolarization. The following iso-electric time (about 100 ms) reflects the propagation of the depolarization through the atrio-ventricular node to the ventricular conduction system. The QRS complex (<120 ms) represents the whole ventricular depolarization, followed by an isoelectric time (about 120 ms) starting from the J point. Finally, the T wave (230-300 ms) represents the final ventricular repolarization and the end of the cycle. Among the various ECG parameters that are useful in analysing the cardiac functions, the QT interval is the most usual one for estimating the ventricular repolarization process. Drug-induced torsade de pointesMany drugs belonging to different pharmacological classes (Table 1) can trigger lifethreatening polymorphic ventricular tachyarrhythmias, such as torsade de pointes. In particular, many non-cardiovascular drugs in common clinical use cause the prolongation

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Life-Threatening Ventricular Arrhythmia (Torsades de Pointes) after Haloperidol Overdose

Cited by 59 publications

References 15 publications

QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

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

Drug-induced block of cardiac HERG potassium channels and development oftorsade de pointesarrhythmias: the case of antipsychotics

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