Drug-Induced QT Interval Prolongation: Mechanisms, Risk Factors, Genetics and Clinical Management

Long QT syndrome (LQTS) characterized by prolongation of the QT interval, may occur as congenital or drug-induced forms. Drug-induced QT interval prolongation (DI-QTP) is closely associated with severe ventricular arrhythmias [especially torsade de pointes (TdP)] and sudden cardiac death. In particular, development of DI-QTP is generally associated with multiple risk factors. Cardiac and non-cardiac drugs may cause QT interval prolongation (QTP) and TdP. Most of the QT-prolonging drugs act by blocking the rapid component of the delayed rectifier potassium channel whereas a smaller number of drugs act by modifying Ca2+ and Na+ currents. In addition, pharmacokinetic drug interactions are among the reasons of DI-QTP. The corrected QT interval (QTc) according to heart rate by Bazett's formula is the most commonly used. Genetic susceptibility is another important issue in predicting DI-QTP and TdP risk. Silent mutations and/or polymorphisms associated with cardiac ion channels may cause a risk for DI-QTP. Firstly, for treatment, drugs that cause QTP should be stopped rapidly, electrolyte abnormalities and other pathologies should be rapidly corrected. Intravenous magnesium sulphate, overdrive pacing, isoproterenol and plasma alkalinisation via sodium bicarbonate are the main useful treatments for DI-QTP and related TdP therapy. Class 1B antiarrhythmic drugs and intravenous potassium are thought to may be effective in TdP

A Case Report of a Pregnant Woman with Chronic Hepatit B: Use of Tenofovir in Pregnancy

Objective: To overview the effects of tenofovir use in chronic Hepatit B in pregnancy and asses the effects on the vertical transmission of HBV from mother to baby

Effect of the selective mitochondrial KATP channel opener nicorandil on the QT prolongation and myocardial damage induced by amitriptyline in rats.

Abstract Objectives The aim of this study is to evaluate the protective effect of nicorandil, a selective mitochondrial KATP channel opener, on QT prolongation and myocardial damage induced by amitriptyline. Methods The dose of amitriptyline (intraperitoneal, i.p.) that prolong the QT interval was found 75 mg/kg. Rats were randomized into five groups the control group, amitriptyline group, nicorandil (selective mitochondrial KATP channel opener, 3 mg/kg i.p.) + amitriptyline group, 5-hdyroxydecanoate (5-HD, selective mitochondrial KATP channel blocker, 10 mg/kg i.p.) + amitriptyline group and 5-HD + nicorandil + amitriptyline group. Cardiac parameters, biochemical and histomorphological/immunohistochemical examinations were evaluated. p &amp;lt; 0.05 was accepted as statistically significant. Key findings Amitriptyline caused statistically significant prolongation of QRS duration, QT interval and QTc interval (p &amp;lt; 0.05). It also caused changes in tissue oxidant (increase in malondialdehyde)/anti-oxidant (decrease in glutathione peroxidase) parameters (p &amp;lt; 0.05), myocardial damage and apoptosis (p &amp;lt; 0.01 and p &amp;lt; 0.001). While nicorandil administration prevented amitriptyline-induced QRS, QT, QTc prolongation (p &amp;lt; 0.05), myocardial damage and apoptosis (p &amp;lt; 0.05), it did not affect the changes in oxidative parameters (p &amp;gt; 0.05). Conclusions Our results suggest that nicorandil, a selective mitochondrial KATP channel opener, plays a protective role in amitriptyline-induced QT prolongation and myocardial damage. Mitochondrial KATP channel opening and anti-apoptotic effects may play a role in the cardioprotective effect of nicorandil. </jats:sec

Parents of ataxia-telangiectasia patients display a distinct cellular immune phenotype mimickingATM-mutated patients

Background Heterozygous relatives of ataxia-telangiectasia (AT) patients are at an increased risk for certain AT-related manifestations. We also show that there is an increase of infection frequency in parents of AT patients. Thus, we hypothesized that the parents might exhibit immune alterations similar to their affected children. Methods Lymphocyte phenotyping to enumerate T- and B-cell subsets was performed. Functional analyses included in vitro quantified gamma-H2AX, poly (ADP-ribose) polymerase (PARP) and caspase-9 proteins. Chromosomal instability was determined by comet assay. Results We analyzed 20 AT patients (14F/6M), 31 parents (16F/15M), and 35 age-matched healthy controls. The AT patients' parents exhibited low frequency of naive CD4(+)T- (n = 14, 45%) and recent thymic emigrants (n = 11, 35%) in comparison with the age-matched healthy donors. Interestingly, parents with low naive T cells also demonstrated high rate of recurrent infections (9/14, 64%). In comparison with age-matched controls, parents who had recurrent infections and low naive T cells showed significantly higher baseline gamma-H2AX levels and H2O2-induced DNA damage as well as increased cleaved caspase-9 and PARP proteins. Conclusion Parents of AT patients could present with recurrent infections and display cellular defects that mimic AT patients. The observed immunological changes could be associated with increased DNA double-strand breaks