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QT drug

Gian Marco Rosa, Danilo Baccino, Alberto Valbusa, Carolina Scala, Fabio Barra, Claudio Brunelli, Simone Ferrero
Overactive bladder (OAB) syndrome is common in the general population, particularly in elderly patients. Antimuscarinic drugs (AMs) are considered the mainstay pharmaceutical treatment of OAB whereas β3-adrenoceptor agonists, such as mirabegron, represent a good alternative. Owing to the important role of muscarinic and β3 receptors in cardiovascular (CV) tissue and to the fact that OAB patients often have CV comorbidities, the safety-profile of these drugs constitute an important challenge. Area covered: The aim of this review is to evaluate the CV effects of AMs and mirabegron in OAB...
March 15, 2018: Expert Opinion on Drug Safety
Nikunjkumar Patel, Oliver Hatley, Alexander Berg, Klaus Romero, Barbara Wisniowska, Debra Hanna, David Hermann, Sebastian Polak
Drug-induced cardiac arrhythmia, especially occurrence of torsade de pointes (TdP), has been a leading cause of attrition and post-approval re-labeling and withdrawal of many drugs. TdP is a multifactorial event, reflecting more than just drug-induced cardiac ion channel inhibition and QT interval prolongation. This presents a translational gap in extrapolating pre-clinical and clinical cardiac safety assessment to estimate TdP risk reliably, especially when the drug of interest is used in combination with other QT-prolonging drugs for treatment of diseases such as tuberculosis...
March 14, 2018: AAPS Journal
Sebastian Polak, Barbara Wiśniowska, Aleksander Mendyk, Adam Pacławski, Jakub Szlęk
Human heart electrophysiology is complex biological phenomenon, which is indirectly assessed by the measured ECG signal. ECG trace is further analyzed to derive interpretable surrogates including QT interval, QRS complex, PR interval, and T wave morphology. QT interval and its modification are the most commonly used surrogates of the drug triggered arrhythmia, but it is known that the QT interval itself is determined by other nondrug related parameters, physiological and pathological. In the current study, we used the computational intelligence algorithms to analyze correlations between various simulated physiological parameters and QT interval...
2018: Computational and Mathematical Methods in Medicine
Sebastian Polak, Klaus Romero, Alexander Berg, Nikunjkumar Patel, Masoud Jamei, David Hermann, Debra Hanna
Cardiotoxicity is among the top drug safety concerns, and is of specific interest in tuberculosis, where this is a known or potential adverse event of current and emerging treatment regimens. As there is a need for a tool, beyond the QT interval, to quantify cardiotoxicity early in drug development, an empirical decision tree based classifier was developed to predict the risk of Torsades de pointes (TdP). The cardiac risk algorithm was developed using pseudo-electrocardiogram (ECG) outputs derived from cardiac myocyte electromechanical model simulations of increasing concentrations of 96 reference compounds which represented a range of clinical TdP risk...
March 8, 2018: Journal of Pharmacokinetics and Pharmacodynamics
Dirk Theile, Gerd Mikus
Recently, the opioid analgesic D,L-methadone has gained much attention as a potential antineoplastic compound, considerably triggered through lay press and media. In consequence, physicians and pharmacists are currently confronted with numerous patients willing to use D,L-methadone against their malignancies. Well-performed in vitro and in vivo models have in fact shown pro-apoptotic effects of D,L-methadone or other opioids, but also proliferation-stimulating properties. Moreover, the mechanisms of proposed opioid-stimulated apoptosis are incompletely described or contradicting...
March 8, 2018: International Journal of Cancer. Journal International du Cancer
Preben Bjerregaard
Establishing a definition of SQTS including symptomatology and QT interval duration is still a work in progress. It is clear, however, that SQTS is a rare, life-threatening, inherited heart disease presenting as SCD or aborted SCD in 34% and a family history of SCD in 15%. Genetic testing is important in diagnosing the disease, but so far with a causative mutation found in less than 25%. A benign variety of the disease has been observed in children with atrial fibrillation and a KCNH2-V141M mutation, and just recently a mutation in the cardiac Cl,HCO3 - exchanger AE3 was found to cause SQTS...
March 1, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Francisco Sahli Costabal, Jiang Yao, Ellen Kuhl
A common but serious side effect of many drugs is torsades de pointes, a rhythm disorder that can have fatal consequences. Torsadogenic risk has traditionally been associated with blockage of a specific potassium channel and an increased recovery period in the electrocardiogram. However, the mechanisms that trigger torsades de pointes remain incompletely understood. Here we establish a computational model to explore how drug-induced effects propagate from the single channel, via the single cell, to the whole heart level...
March 1, 2018: Computer Methods in Biomechanics and Biomedical Engineering
Bharath Yarlagadda, Venkat Vuddanda, Tawseef Dar, Mohammad-Ali Jazayeri, Valay Parikh, Mohit K Turagam, Madhav Lavu, Sindhu Reddy Avula, Donita Atkins, Sudharani Bommana, Rakesh Gopinathannair, Madhu Reddy Yeruva, Dhanunjaya Lakkireddy
Background: We sought to investigate and compare the safety and efficacy of two commonly used antiarrhythmic drugs, Dofetilide (DF) and Sotalol (SL), during inpatient drug initiation in patients with symptomatic atrial fibrillation (AF). Methods: We performed a single center retrospective study of consecutive patients, admitted for initiation of either DF or SL, for AF between 2012 and 2015. Rates of successful cardioversion, QT interval prolongation, adverse events and drug discontinuations were calculated and compared...
December 2017: Journal of Atrial Fibrillation
Mirjam Simoons, Adrie Seldenrijk, Hans Mulder, Tom Birkenhäger, Mascha Groothedde-Kuyvenhoven, Rob Kok, Cornelis Kramers, Wim Verbeeck, Mirjam Westra, Eric van Roon, Roberto Bakker, Henricus Ruhé
Currently, there is a lack of international and national guidelines or consensus documents with specific recommendations for electrocardiogram (ECG) screening and monitoring during antidepressant treatment. To make a proper estimation of the risk of cardiac arrhythmias and sudden (cardiac) death during antidepressant use, both the drug and patient-specific factors should be taken into account; however, solid evidence on how this should be done in clinical practice is lacking. Available recommendations on the management of QT(c) prolongation (with antidepressant treatment) emphasize that special attention should be given to high-risk patients; however, clinicians are in need of more concrete suggestions about how to select patients for ECG screening and monitoring...
February 26, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Mena Abdelsayed, Manpreet Ruprai, Peter C Ruben
E1784K is the most common mixed syndrome SCN5a mutation underpinning both Brugada syndrome type 1 (BrS1) and Long-QT syndrome type 3 (LQT3). The charge reversal mutant enhances the late sodium current (INa ) passed by the cardiac voltage-gated sodium channel (NaV 1.5), delaying cardiac repolarization. Exercise-induced triggers, like elevated temperature and cytosolic calcium, exacerbate E1784K late INa . In this study, we tested the effects of Ranolazine, the late INa blocker, on voltage-dependent and kinetic properties of E1784K at elevated temperature and cytosolic calcium...
February 26, 2018: Scientific Reports
Igor Baburin, Rosanne Varkevisser, Anja Schramm, Priyanka Saxena, Stanislav Beyl, Phillip Szkokan, Tobias Linder, Anna Stary-Weinzinger, Marcel A G van der Heyden, Marien Houtman, Hiroki Takanari, Malin Jonsson, Jet H D Beekman, Matthias Hamburger, Marc A Vos, Steffen Hering
Evodiae fructus is a widely used herbal drug in traditional Chinese medicine. Evodia extract was found to inhibit hERG channels. The aim of the current study was to identify hERG inhibitors in Evodia extract and to investigate their potential proarrhythmic effects. Dehydroevodiamine (DHE) and hortiamine were identified as IKr (rapid delayed rectifier current) inhibitors in Evodia extract by HPLC-microfractionation and subsequent patch clamp studies on human embryonic kidney cells. DHE and hortiamine inhibited IKr with IC50 s of 253...
February 22, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Cecilia Villa Etchegoyen, Guillermo Alberto Keller, Sebastian Mrad, Sixuan Cheng, Guillermo DiGirolamo
Drug-induced QT interval prolongation is the most frequent cause of Long QT syndrome (LQTS) in the clinical practice. This electrophysiological entity, produced by an extended duration of the myocardial repolarization and reflected as a prolonged QT interval in the superficial electrocardiogram (EKG), increases the risk of polymorphic ventricular tachycardia (Torsades de Pointes) appearance and sudden death. Certain antiarrhythmic drugs such as amiodarone, sotalol, quinidine, procainamide, verapamil and diltiazem are known as drugs that, due to their mechanism of action, prolong the QT interval, demanding constant monitorization...
February 23, 2018: Current Clinical Pharmacology
Frederik Marmé, Carlos Gomez-Roca, Kristina Graudenz, Funan Huang, John Lettieri, Carol Peña, Zuzana Jirakova Trnkova, Jan Eucker
Combining sorafenib and eribulin mesylate may provide synergistic antitumor activities with limited overlapping toxicities. This phase 1b, open-label, dose-escalation study evaluated safety, pharmacokinetics, maximum tolerated dose/recommended phase 2 dose (MTD/RP2D), and preliminary efficacy of sorafenib plus standard-dose eribulin mesylate in patients with advanced, metastatic, or refractory tumors. Patients received sorafenib 200 mg twice daily (BID; n = 5), 600 mg/day (n = 8), and 400 mg BID (MTD; n = 27)...
February 21, 2018: Cancer Chemotherapy and Pharmacology
Jussi T Koivumäki, Nikolay Naumenko, Tomi Tuomainen, Jouni Takalo, Minna Oksanen, Katja A Puttonen, Šárka Lehtonen, Johanna Kuusisto, Markku Laakso, Jari Koistinaho, Pasi Tavi
Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising experimental tool for translational heart research and drug development. However, their usability as a human adult cardiomyocyte model is limited by their functional immaturity. Our aim is to analyse quantitatively those characteristics and how they differ from adult CMs. Methods and Results: We have developed a novel in silico model with all essential functional electrophysiology and calcium handling features of hiPSC-CMs...
2018: Frontiers in Physiology
Gudrun Hefner, Martina Hahn, Matthias Hohner, Sybille C Roll, Ansgar Klimke, Christoph Hiemke
INTRODUCTION: Many antidepressants cause QT prolongation but the classification of cardiac risk of these drugs varies markedly in different published lists. This retrospective study analyzed the correlation of QTc time with amitriptyline and venlafaxine serum level in elderly psychiatric inpatients. METHODS: Elderly inpatients aged≥65 years for whom venlafaxine or amitriptyline serum level had been measured were selected retrospectively from a therapeutic drug monitoring database and screened for an electrocardiogram measurement at the time of blood withdrawal...
February 21, 2018: Pharmacopsychiatry
Jerónimo Auzmendi, Bruno Buchholz, Jimena Salguero, Carlos Cañellas, Jazmín Kelly, Paula Men, Marcela Zubillaga, Alicia Rossi, Amalia Merelli, Ricardo J Gelpi, Alberto J Ramos, Alberto Lazarowski
Sudden unexpected death in epilepsy (SUDEP) is the major cause of death in those patients suffering from refractory epilepsy (RE), with a 24-fold higher risk relative to the normal population. SUDEP risk increases with seizure frequency and/or seizure-duration as in RE and Status Epilepticus (SE). P-glycoprotein (P-gp), the product of the multidrug resistant ABCB1-MDR-1 gene, is a detoxifying pump that extrudes drugs out of the cells and can confer pharmacoresistance to the expressing cells. Neurons and cardiomyocytes normally do not express P-gp, however, it is overexpressed in the brain of patients or in experimental models of RE and SE...
February 16, 2018: Pharmaceuticals
Annelies Decloedt, Barbara Broux, Dominique De Clercq, Piet Deprez, Glenn Van Steenkiste, Lisse Vera, Sofie Ven, Gunther van Loon
BACKGROUND: Based on its pharmacokinetic profile and electrophysiological effects in healthy horses, sotalol potentially could be used as a long-term PO antiarrhythmic drug in horses. OBJECTIVES: To evaluate the effect of sotalol on heart rate (HR), QT interval, atrial fibrillatory rate, and success of cardioversion in horses with naturally occurring chronic atrial fibrillation (AF). ANIMALS: Twenty-eight horses referred for transvenous electrical cardioversion of AF were treated with 2 mg/kg sotalol PO q12h for 3 days before cardioversion, and 13 horses underwent the same protocol without sotalol administration...
February 20, 2018: Journal of Veterinary Internal Medicine
Qasim Khan, Mohammad Ismail, Iqbal Haider, Zahid Ali
BACKGROUND/PURPOSE: Medical inpatients are at increased risk of QT interval prolongation due to multiple risk actors and QT prolonging drugs. This study aimed to identify the prevalence of risk factors for QT prolongation; QT prolonging medications; associated drug-drug interactions (QT-DDIs); their predictors; and TdP (torsades de pointes) risks of drugs. METHODS: This cohort study was carried out in medical wards of two tertiary hospitals in Khyber Pakhtunkhwa, Pakistan...
February 16, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Rezvan Enteshari Najafabadi, Nasrin Kazemipour, Abolghasem Esmaeili, Siamak Beheshti, Saeed Nazifi
Background: Superparamagnetic iron oxide nanoparticles (SPION) have been largely considered for numerous applications in biomedicine such as magnetic resonance imaging, hyperthermia, cell tracking, anticancer treatment, and targeted delivery of drugs or genes. However, they may have side effects such body weight loss. Quercetin (QT), a strong antioxidant and free radical scavenger and a natural flavonoid, has a wide range of biological and therapeutic effects. In this study, the effect of QT on prevention of weight loss due to the using of SPION has been investigated...
2018: Advanced Biomedical Research
Tolga Tolunay, Vedat Bicici, Hatice Tolunay, Mehmet Orcun Akkurt, Arslan Kagan Arslan, Ali Aydogdu, Izzet Bingol
INTRODUCTION: Cast room procedures generally cause anxiety in patients. Anxiety complicates the procedure as well as increases the risk of a complication. Listening to music was found to be the safest and most common non-drug treatment method. The aim of this study is to evaluate the effect of listening to music on adult patients in cast room procedures. This study points out the relation between anxiety and anxiety relevant cardiac arrhythmia. MATERIALS AND METHODS: The study was performed on 199 patients with stable general condition, aged above 18...
February 7, 2018: Injury
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