Ziprasidone and hypokalemia: a case of 2 predisposing factors for QTc prolongation without development of torsades de pointes.

نویسندگان

  • B Rush Simpson
  • Robert P Albanese
چکیده

Sir: Although concerns about sudden cardiac arrhythmia death associated with the use of an antipsychotic drug actually predate the description of torsades de pointes, it is this fatal arrhythmia and its electrocardiographic (ECG) predictor (corrected QT [QTc] interval prolongation) that have become of increasing concern related to the use of antipsychotic medications during recent years. The first case reports of patients dying from a fatal arrhythmia while taking an antipsychotic medication appeared in 1963, and 3 years later torsades de pointes was described. Although it would be some years before these 2 phenomena were linked, with similar cases mounting, the reality of antipsychotic medication–induced torsades de pointes has since become an entity that those prescribing these medications must guard against. Torsades de pointes is a term that refers to polymorphic ventricular tachycardia that occurs in the setting of an abnormally long QT interval. The most common cause of this arrhythmia is treatment with a drug that prolongs the QT interval. The QT interval is an ECG measurement that encompasses both depolarization and repolarization of the ventricle. Depolarization of the ventricle is primarily due to rapid influx of sodium ions through sodium channels, and its duration is represented electrocardiographically by the QRS interval. Repolarization, the duration of which is represented by the ST segment, involves sodium, potassium, and calcium channels. Although altering either of these components can yield arrhythmias, some antipsychotic medications prolong the QT interval through their effects on repolarization. More specifically, it is through a potassium channel that drug-induced QT prolongation is achieved. This potassium channel is the potassium rectifier channel (I Kr). Therefore, drugs that block the I Kr channel can induce QT prolongation and subsequent sudden cardiac death from torsades de pointes in otherwise healthy patients. Given this effect, QT intervals should be followed when patients are treated with medications that can significantly prolong the QT interval. Since the QT interval shortens with increasing heart rate, it is usually corrected for heart rate, and this corrected interval is known as the QTc interval. An absolute QTc interval greater than 500 msec, or an increase of 60 msec from baseline, is a surrogate marker for the ability of a drug to cause torsades de pointes. Although for many years the antipsychotic drug of most concern in this realm was thioridazine, in 1996 a new atypical antipsychotic, sertindole, was not registered in the United States because it prolonged the QTc interval and was associated with 12 sudden unexplained deaths in Europe. These concerns arose again when ziprasidone showed a modest effect on QTc interval during clinical trials. During these studies, patients treated with ziprasidone showed a QTc interval increase of 20.3 msec from baseline. Although this prolongation was somewhat less than that produced by thioridazine (35.6 msec), enough concern developed surrounding ziprasidone that it initially became common practice among many physicians to check baseline and periodic ECGs when employing ziprasidone therapy. While this practice has waned with time, concerns remain in the psychiatric community about ziprasidone’s QTc effects. As previously mentioned, QT-prolonging drugs are the most common cause of torsades de pointes; however, other factors such as congenital long QT syndromes and electrolyte abnormalities can also prolong the QT interval and induce torsades de pointes. Hypokalemia is the most notable of QT-prolonging electrolyte abnormalities. Even modest hypokalemia with potassium levels in the range of 2.8 to 3.5 mmol/L has been shown to prolong the QTc interval to 660 msec. Although hypokalemia has been shown as an independent variable to be a significant inducer of QTc prolongation and torsades de pointes, it also has been noted to trigger torsades de pointes in patients with other QTc prolongation issues. For example, hypokalemia was noted to trigger torsades de pointes in some groups of individuals with congenital long QT syndrome. Further, experimental models have shown that the pharmacologic blockade of I Kr by antiarrhythmics such as quinidine and dofetilide is increased proportionally with decreasing potassium concentrations. Given the above, it would be of both clinical concern and interest if a patient who was taking full-dose ziprasidone were to present with hypokalemia.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

QTc prolongation, torsades de pointes, and psychotropic medications.

BACKGROUND Prolongation of the corrected QT (QTc) interval is a key issue for patients who receive psychotropic medications. Such patients may have baseline clinical risk factors for QTc prolongation, and many psychotropic medications may further prolong this interval. This has great clinical relevance, as QTc prolongation is linked with dangerous arrhythmias, especially torsades de pointes (Td...

متن کامل

QTc prolongation by psychotropic drugs and the risk of Torsade de Pointes.

INTRODUCTION Many psychotropic drugs can delay cardiac repolarization and thereby prolong the rate-corrected QT interval (QTc). A prolonged QTc often arouses concern in clinical practice, as it can be followed, in rare cases, by the life-threatening polymorphic ventricular tachyarrhythmia called torsade de pointes (TdP). METHOD We searched PubMed for pertinent literature on the risk of QTc pr...

متن کامل

Torsade de Pointes and Persistent QTc Prolongation after Intravenous Amiodarone

We report a case of torsade de pointes after intravenous amiodarone and concurrent hypokalemia. Despite treatment cessation and correction of electrolyte abnormalities, excessive QTc prolongation was noted, which persisted for 14 days. This prolonged course for QTc normalization may be attributed to the high rate of amiodarone loading and concurrent electrolyte disturbances coupled with possibl...

متن کامل

Ciprofloxacin induced acquired long QT syndrome in a patient under class III antiarrhythmic therapy.

We report one case of cardiac arrest related to ciprofloxacin administration. One female patient (aged 70 years old) developed a marked QTc prolongation (QTc = 0.62 s) within 24 hours of ciprofloxacin administration, with documented torsades de pointes and recurrent syncope that required defibrillation. The patient was under amiodarone and sotalol therapy for atrial fibrillation, with no obviou...

متن کامل

QT interval prolongation and torsades de pointes in a patient undergoing treatment with vorinostat: a case report and review of the literature.

Vorinostat is a histone deacetylase inhibitor used in the treatment of recurrent or persistent cases of cutaneous T-cell lymphoma (CTCL). A retrospective review of 116 patients from phase I and II clinical trials who had a baseline and at least one subsequent ECG revealed that four patients had Grade 2 and one patient had Grade 3 QTc interval prolongation; however, a MEDLINE search found no rep...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Primary care companion to the Journal of clinical psychiatry

دوره 7 3  شماره 

صفحات  -

تاریخ انتشار 2005