1.
Long QT syndrome caused by noncardiac drugs.
Viskin, S, Justo, D, Halkin, A, Zeltser, D
Progress in cardiovascular diseases. 2003;(5):415-27
Abstract
Numerous medications not intended for cardiac use (including antibiotics, histamine blockers, and antipsychotic medications) incidentally block potassium channels in myocardial cells, prolong the QT interval, and may trigger malignant arrhythmias. Although the odds for a given patient for developing arrhythmias are small, the number of patients receiving such drugs is enormous. Most patients developing proarrhythmia have additional risk factors that could be easily identified from their medical history. The list of risk factors includes female gender, organic heart disease, hypokalemia, and a history of long QT or drug-induced arrhythmias. Patients without risk factors are at very low risk. For these patients, it is neither practical nor necessary to record an electrocardiogram before therapy is initiated and the most important preventive measure is to avoid concurrent administration of 2 or more drugs that prolong the QT interval or administration of a medication that impairs the metabolism of a QT-prolonging drug. We performed a computerized literature search using the key words "long QT," "torsade," "drug-adverse effects," and "drug-ventricular arrhythmias," searching for published reports of drug-induced torsade de pointes. The references in each of these reports also were reviewed to identify additional publications. In addition, we reviewed the published reviews and the Internet sites dealing with drug-induced arrhythmias. All the original articles quoted in these reviews and Web sites were examined critically.
2.
Diazoxide in the treatment of schizophrenia: novel application of potassium channel openers in the treatment of schizophrenia.
Akhondzadeh, S, Mojtahedzadeh, V, Mirsepassi, GR, Moin, M, Amini-Nooshabadi, H, Kamalipour, A
Journal of clinical pharmacy and therapeutics. 2002;(6):453-9
Abstract
OBJECTIVE Schizophrenia is a very common disorder, affecting 1% of the world population. People who develop schizophrenia experience severe suffering and approximately 10% commit suicide. The causes of schizophrenia are still largely unknown. The relative ineffectiveness of dopamine antagonists to treat some symptoms of schizophrenia has promoted many investigators to postulate the involvement of the neuronal system in the pathophysiology of this disease. It has been suggested that the dopamine-coupled adenosine triphosphate (ATP)-sensitive channels may function by hyperpolarizing cells during metabolic stress, a function that may be disrupted in people with schizophrenia. Therefore, application of potassium channel openers/activators may be beneficial in schizophrenia. Diazoxide is a benzothiadiazine derivative related to the thiazide diuretics and a potassium channel opener. The purpose of the present investigation was to assess the efficacy of diazoxide, as an adjuvant agent in the treatment of schizophrenia. METHODS Forty-two patients who met the DSM IV criteria for chronic schizophrenia completed the study. Patients were randomized to haloperidol 20 mg/day plus diazoxide 200 mg/day (21 subjects) or to haloperidol 20 mg/day plus placebo (21 subjects) in this 8-week double-blind study. RESULTS Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of haloperidol and diazoxide showed a significant superiority over haloperidol alone in the treatment of positive and general psychopathology symptoms as well as positive and negative syndrome scale (PANSS) total scores. In addition, in the diazoxide group a rapid onset of action on the positive symptoms was observed in week 2, whereas in the placebo group there was no significant effect at week 2. No significant differences were observed between the two protocols on the negative scores. CONCLUSION The results of this study present a novel application for potassium channel openers/activators in the neuropsychiatric disorders and diazoxide may be an effective adjuvant agent in the management of schizophrenia.