[Cardiac effects of antipsychotics: mechanism of arrhythmias and sudden cardiac death].
The review summarizes experimental and clinical data showing the cardiac side effects of antipsychotic drugs. Some antipsychotics may correlate with prolongation of QT interval, induce ventricular tachycardia, torsades de pointes, TdP, and sudden death. The author surveys the cellular actions of the drugs, the electrophysiological mechanisms and the recent data referring the drug's effects on ionic currents, mainly potassium currents. Most antipsychotics are associated with the inhibition of delayed rectifier K+ channels. Comparing the potency on K+ channel inhibition and the prolongation of the QT interval with the therapeutic plasma levels of the drugs, the difference between the inhibitory potency and the therapeutic dose is the highest in the case of quetiapine, olanzepine and risperidone, while thioridazine shows the smallest difference. All drugs that cause TdP prolong the QT interval and inhibit the K+ rectifier channel, but the relationship is not precise. Some additional cellular effects of particular agents, modulating conditions, factors (diseases, electrolytes disturbances, genetic damage, drug interactions) make the individual vulnerable to arrhythmia. The paper highlights drug interactions causing risk of arrhythmia during chronic treatment of psychiatric patients.
Kecskeméti
Valéria
V
Semmelweis Egyetem, Altalános Orvostudományi Kar, Farmakológiai és Farmakoterápiás Intézet, Budapest. kecsval@pharma.sote.hu
D000200:Action Potentials / Q000187:drug effects; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology; D015221:Potassium Channels / Q000187:drug effects*; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000503:physiopathology; D016171:Torsades de Pointes / Q000139:chemically induced / Q000503:physiopathology
D014150:Antipsychotic Agents; D015221:Potassium Channels