The association between intravenous haloperidol and Torsades de Pointes. Three cases and a literature review.
ABSTRACT Torsades de Pointes (TDP) is a potentially malignant ventricular arrhythmia that often has a drug-induced origin. Oral, but not intravenous, haloperidol has been generally associated with this arrhythmia. The authors detail three patient cases of TDP that occurred while the patients were receiving intravenous haloperidol. The authors discuss the known risk factors for the development of TDP and review the literature on ventricular arrhythmias associated with haloperidol use.
SourceAvailable from: Jaromir Gumulec[Show abstract] [Hide abstract]
ABSTRACT: Haloperidol (HP) is used for the symptomatic treatment of psychosis, manic phases, hyperactivity, aggressiveness, and acute delirium. Long-term use leads to various adverse side effects, especially to severe impairment of extrapyramidal nerve tracts and in particular, altered QT interval and increased incidence of arrhytmias. It is believed that cytotoxicity of HP and its metabolites is responsible for both neurotoxicity and cardiotoxicity. Extrapyramidal and cardiac adverse side effects may be explained by the HP-induced oxidative stress, as implicated by many studies. HP was reported to induce lipid peroxidation with subsequent membrane changes, responsible for cell death. Vice versa, cells resistant to oxidative stress are also resistant to the toxic effects of HP. Similarly, high percentage of patients suffering from extrapyramidal symptoms treated by vitamin E and other lipid-soluble antioxidants demonstrates diminishing of these adverse side effects. HP's ability to induce oxidative stress by multi-modal action (increased metabolism of dopamine, decrease of glutathione content, induction of NF-κB transcription factor, and inhibition of complex I of respiratory chain) has been established just recently. This review brings summarizing view on the cytotoxicity of haloperidol and involvement of reactive oxygen species and oxidative stress HP-induced cytotoxicity.Mini Reviews in Medicinal Chemistry 10/2013; 13(14):1993-1998. DOI:10.2174/13895575113136660100 · 3.19 Impact Factor
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ABSTRACT: Haloperidol is commonly used in clinical practice to treat acute and chronic psychosis, but it also has been associated with adverse cardiovascular events. We investigated the effects of haloperidol on Kv4.3 currents stably expressed in CHO cells using a whole-cell patch-clamp technique. Haloperidol did not significantly inhibit the peak amplitude of Kv4.3, but accelerated the decay rate of inactivation of Kv4.3 in a concentration-dependent manner. Thus, the effects of haloperidol on Kv4.3 were estimated from the integral of the Kv4.3 currents during the depolarization pulse. The Kv4.3 was decreased by haloperidol in a concentration-dependent manner with an IC50 value of 3.6μM. Haloperidol accelerated the decay rate of Kv4.3 inactivation and activation kinetics in a concentration-dependent manner, thereby decreasing the time-to-peak. Haloperidol shifted the voltage dependence of the steady-state activation and inactivation of Kv4.3 in a hyperpolarizing direction. Haloperidol also caused an acceleration of the closed-state inactivation of Kv4.3. Haloperidol produced a use-dependent block of Kv4.3, which was accompanied by a slowing of recovery from the inactivation of Kv4.3. These results suggest that haloperidol blocks Kv4.3 by both interacting with the open state of Kv4.3 channels during depolarization and accelerating the closed-state inactivation at subthreshold membrane potentials.European Journal of Pharmacology 07/2014; DOI:10.1016/j.ejphar.2014.06.043 · 2.68 Impact Factor
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ABSTRACT: Antipsychotic drugs have been associated with sudden cardiac death, but differences in the risk of out-of-hospital cardiac arrest (OHCA) associated with different antipsychotic drug classes are not clear. We identified all OHCA in Denmark (2001-2010). Risk of OHCA associated with antipsychotic drug use was evaluated by conditional logistic regression analysis in case-time-control models. In total, 2,205 (7.6%) of 28,947 OHCA patients received treatment with an antipsychotic drug at the time of event. Overall treatment with any antipsychotic was associated with OHCA (odds ratio [OR]= 1.53, 95% confidence interval [CI]:1.23-1.89) as was use with typical antipsychotics (OR= 1.66, CI: 1.27-2.17). By contrast, overall atypical antipsychotics drug use was not (OR= 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs were associated with OHCA, haloperidol (OR= 2.43, CI: 1.20-4.93) and levomepromazine (OR= 2.05, CI: 1.18-3.56) as was one atypical antipsychotic, quetiapine (OR= 3.64, CI: 1.59-8.30).Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 24 June 2014; doi:10.1038/clpt.2014.139.Clinical Pharmacology & Therapeutics 06/2014; 96(4). DOI:10.1038/clpt.2014.139 · 7.39 Impact Factor