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Alessandro Capucci, Laura Cipolletta, Federico Guerra, Irene Giannini
The main aim of current research on the field of atrial fibrillation (AF) treatment is to find new antiarrhythmic drugs with less side effects. Areas covered: Dronedarone and vernakalant showed promising result in term of efficacy and safety in selected patients. Ranolazine and colchicine are obtaining a role as a potential antiarrhythmic drug. Ivabradine is used in experimental studies for the rate control of AF. Moreover, new compounds (vanoxerine, moxonidine, budiodarone) are still under investigation. Monoclonal antibodies or selective antagonist of potassium channel are under investigation for long term maintenance of sinus rhythm...
March 6, 2018: Expert Opinion on Emerging Drugs
Chuntao Wu, Stephanie Tcherny-Lessenot, Wanju Dai, Yunxun Wang, Hayet Kechemir, Sampada Gandhi, Stephen Lin, Juhaeri Juhaeri
PURPOSE: There are few data on the risk for peripheral neuropathy associated with dronedarone, a newer antiarrhythmic medicine. The objective of this study was to assess whether dronedarone is potentially associated with an increased risk for peripheral neuropathy compared with other antiarrhythmics, including amiodarone, sotalol, flecainide, and propafenone. METHODS: The MarketScan database was used for identifying patients who were at least 18 years of age, had atrial fibrillation or flutter, and had not been diagnosed with peripheral neuropathy in the 180-day period prior to or on the date of the first prescription of an antiarrhythmic between July 20, 2009, and December 31, 2011...
February 27, 2018: Clinical Therapeutics
María Isabel Guzmán Ramos, Teresa Romero García, Esther Márquez Sánchez, Emilio Suárez García, Rubén Martínez Castillo
No abstract text is available yet for this article.
February 13, 2018: Gastroenterología y Hepatología
Si Chen, Zhen Ren, Dianke Yu, Baitang Ning, Lei Guo
Dronedarone, an antiarrhythmic drug, has been marketed as an alternative to amiodarone. The use of dronedarone has been associated with severe liver injury; however, the mechanisms remain unclear. In this study, the possible mechanisms of dronedarone induced liver toxicity were characterized in HepG2 cells. Dronedarone decreased cells viability and induced apoptosis and DNA damage in a concentration- and time-dependent manner. Pretreatment of the HepG2 cells with apoptosis inhibitors (caspase-3, -8, and -9) or the necrosis inhibitor (Necrox-5), partially, but significantly, reduced the release of lactate dehydrogenase...
February 5, 2018: Environmental and Molecular Mutagenesis
Aneesh Karkhanis, Jacqueline Wen Hui Leow, Thilo Hagen, Eric Chun Yong Chan
Dronedarone and amiodarone are structurally similar antiarrhythmic drugs. Dronedarone worsens cardiac adverse effects with unknown causes while amiodarone has no cardiac adversity. Dronedarone induces preclinical mitochondrial toxicity in rat liver and exhibits clinical hepatotoxicity. Here, we further investigated the relative potential of the antiarrhythmic drugs in causing mitochondrial injury in cardiomyocytes. Differentiated rat H9c2 cardiomyocytes were treated with dronedarone, amiodarone and their respective metabolites namely N-desbutyldronedarone (NDBD) and N-desethylamiodarone (NDEA)...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Ilia G Denisov, Javier L Baylon, Yelena V Grinkova, Emad Tajkhorshid, Stephen G Sligar
Heterotropic interactions between atorvastatin (ARVS) and dronedarone (DND) have been deciphered using global analysis of the results of binding and turnover experiments for pure drugs and their mixtures. The in vivo presence of atorvastatin lactone (ARVL) was explicitly taken into account by using pure ARVL in analogous experiments. Both ARVL and ARVS inhibit DND binding and metabolism, while a significantly higher affinity of CYP3A4 for ARVL makes the latter the main modulator of activity (effector) in this system...
February 6, 2018: Biochemistry
Hyeongsoo Kim, Tae Hoon Kim, Myung Jin Cha, Jung Myung Lee, Junbeom Park, Jin Kyu Park, Ki Woon Kang, Jaemin Shim, Jae Sun Uhm, Jun Kim, Hyung Wook Park, Eue Keun Choi, Jin Bae Kim, Changsoo Kim, Young Soo Lee, Boyoung Joung
BACKGROUND AND OBJECTIVES: The aging population is rapidly increasing, and atrial fibrillation (AF) is becoming a significant public health burden in Asia, including Korea. This study evaluated current treatment patterns and guideline adherence of AF treatment. METHODS: In a prospective observational registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF] registry), 6,275 patients with nonvalvular AF were consecutively enrolled between June 2016 and April 2017 from 10 tertiary hospitals in Korea...
November 2017: Korean Circulation Journal
Begoña Quintana-Villamandos, Jose Juan Gomez de Diego, María Jesús Delgado-Martos, David Muñoz-Valverde, María Luisa Soto-Montenegro, Manuel Desco, Emilio Delgado-Baeza
BACKGROUND AND AIMS: Left ventricular hypertrophy (LVH) in hypertension is associated with a greater risk of sustained supraventricular/atrial arrhythmias. Dronedarone is an antiarrhythmic agent that was recently approved for the treatment of atrial fibrillation. However, its effect on early regression of LVH has not been reported. We tested the hypothesis that short-term administration of dronedarone induces early regression of LVH in spontaneously hypertensive rats (SHRs). METHODS: Ten-month-old male SHRs were randomly assigned to an intervention group (SHR-D), where animals received dronedarone treatment (100 mg/kg) for a period of 14 days, or to a control group (SHR) where rats were given vehicle...
2017: PloS One
Yoshiyuki Motokawa, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Hiroko Izumi-Nakaseko, Kentaro Ando, Atsuhiko T Naito, Hiroshi Yamazaki, Atsushi Sugiyama
Anti-atrial fibrillatory, proarrhythmic and cardiodepressive profiles of dronedarone were analyzed using the halothane-anesthetized beagle dogs (n = 4) to create a standard protocol for clarifying both efficacy and adverse effects of anti-atrial fibrillatory drugs. Intravenous administration of dronedarone hydrochloride in doses of 0.3 and 3 mg/kg over 30 s attained the peak plasma concentrations of 61 and 1248 ng/mL, respectively, reflecting sub- to supra-therapeutic ones. The low dose decreased the left ventricular contraction and mean blood pressure, which were enhanced at the high dose...
November 14, 2017: Cardiovascular Toxicology
M Urooj Zafar, Carlos G Santos-Gallego, Donald A Smith, Jonathan L Halperin, Juan J Badimon
BACKGROUND AND AIMS: Dronedarone reduced the rate of stroke and transient ischemic attack in patients with paroxysmal atrial fibrillation (AF) in the ATHENA trial. This cannot be explained by its antiarrhythmic effect alone and may involve alternative mechanisms. This study aimed to investigate any direct effect of dronedarone on blood thrombogenicity, independent of its antiarrhythmic effects. METHODS: Blood samples from patients with cardiovascular disease (n = 30) taking no anticoagulant or antiplatelet medication except aspirin were incubated with dronedarone's active metabolite (SR35021A) at 66 ng/ml (am-L) and 119 ng/ml (am-H), i...
November 2017: Atherosclerosis
Shang-Hung Chang, I-Jun Chou, Yung-Hsin Yeh, Meng-Jiun Chiou, Ming-Shien Wen, Chi-Tai Kuo, Lai-Chu See, Chang-Fu Kuo
Importance: Non-vitamin K oral anticoagulants (NOACs) are commonly prescribed with other medications that share metabolic pathways that may increase major bleeding risk. Objective: To assess the association between use of NOACs with and without concurrent medications and risk of major bleeding in patients with nonvalvular atrial fibrillation. Design, Setting, and Participants: Retrospective cohort study using data from the Taiwan National Health Insurance database and including 91 330 patients with nonvalvular atrial fibrillation who received at least 1 NOAC prescription of dabigatran, rivaroxaban, or apixaban from January 1, 2012, through December 31, 2016, with final follow-up on December 31, 2016...
October 3, 2017: JAMA: the Journal of the American Medical Association
Mohammed Hasan Khan, Yogita Rochlani, Wilbert S Aronow
Dronedarone, a derivative of amiodarone with structural modifications, was designed to have similar electrophysiological properties with a less toxic profile. Areas covered: Brief overview of the pharmacology of dronedarone followed by a summary of randomized clinical trials testing the efficacy of dronedarone in maintaining normal sinus rhythm and clinical outcomes associated with these trials. In depth discussion and commentary on trial findings which may seem contradictory at first approach and brief discussion of post-marketing surveillance studies...
December 2017: Expert Opinion on Drug Safety
Aneesh Karkhanis, Nhan Dai Thien Tram, Eric Chun Yong Chan
Cardiac enzymes such as cytochrome P450 2J2 (CYP2J2) metabolize arachidonic acid (AA) to cardioprotective epoxyeicosatrienoic acids (EETs), which in turn are metabolized by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs). As EETs and less potent DHETs exhibit cardioprotective and vasoprotective functions, optimum levels of cardiac EETs are paramount in cardiac homeostasis. Previously, we demonstrated that dronedarone, amiodarone and their main metabolites, namely N-desbutyldronedarone (NDBD) and N-desethylamiodarone (NDEA), potently inhibit human cardiac CYP2J2-mediated astemizole metabolism in vitro...
December 15, 2017: Biochemical Pharmacology
Min-Soo Kim, In-Hwan Baek
Dronedarone is a CYP2D6 inhibitor; therefore, it is prudent to exercise caution when concurrently administering CYP2D6-metabolized β-blockers because of a lack of published data on potential drug interactions. The aim of this study was to investigate the effect of dronedarone on the pharmacokinetics of orally administered carvedilol in rats. Twenty male Sprague-Dawley rats were randomly divided into two groups and 10mg/kg carvedilol was administered to the rat with or without dronedarone pretreatment in a parallel design...
September 20, 2017: European Journal of Pharmaceutical Sciences
Ruth María Sánchez Soriano, Carlos Israel Chamorro Fernández, Juan Miguel Ruiz Nodar, Antonio Javier Chamorro Fernández, Guillermo Grau Jornet, Julio Nuñez Villota
INTRODUCTION AND OBJECTIVES: Dronedarone and flecainide are the first pharmacological choice to reduce recurrence of atrial fibrillation (AF); however, there are no studies comparing them. A study was performed to compare the efficacy in terms of recurrence of AF and safety of both drugs. METHODS: A retrospective cohort study was conducted that included 123 consecutive patients treated with flecainide or dronedarone due to paroxysmal AF (76.4%) or persistent AF (23...
August 30, 2017: Archivos de Cardiología de México
Thomas Cars, Lars Lindhagen, Rickard Malmström, Martin Neovius, Jonas Schwieler, Björn Wettermark, Johan Sundström
Although there is no doubt about the scientific value of randomized controlled clinical trials, they are usually conducted in selected populations different from those treated in clinical practice. Therefore, it is important to optimize real-time post-marketing evaluation of effectiveness, safety, and cost of new drugs. Using electronic health records and administrative health databases from a well-defined region with universal access to healthcare, we have built a framework for real-time sequential monitoring of the effectiveness of newly marketed drugs in routine care...
May 30, 2017: Clinical Pharmacology and Therapeutics
Yuan Ji, Hiroki Takanari, Muge Qile, Lukas Nalos, Marien J C Houtman, Fee L Romunde, Raimond Heukers, Paul M P van Bergen En Henegouwen, Marc A Vos, Marcel A G van der Heyden
Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely unknown. KIR 2.1 inward rectifier channels, largely responsible for the cardiac inward rectifier current (IK1 ), are degraded in lysosomes. Amiodarone and dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a lesser extent dronedarone, causes serious adverse effects to several organs and tissue types, including the heart. Both drugs have been described to interfere in the late-endosome/lysosome system...
October 2017: Journal of Cellular and Molecular Medicine
Nakkawee Saengklub, Vudhiporn Limprasutr, Suwanakiet Sawangkoon, Robert L Hamlin, Anusak Kijtawornrat
Atrial fibrillation (AF) is a supraventricular arrhythmia that leads to a decrease in cardiac output and impairs cardiac function and quality of life. Dronedarone has an atrial-selective property and has been used for management of AF in humans, but limited information is available in dogs. This study was designed to evaluate efficacy of dronedarone in attenuating the duration of AF in dog model of sustained AF. Six beagle dogs were anesthetized with isoflurane and instrumented to measure atrial action potential duration (aAPD) and atrial effective refractory period (AERP)...
August 5, 2017: Experimental Animals
Izna Ali, Matthew A Welch, Yang Lu, Peter W Swaan, Kim L R Brouwer
INTRODUCTION: Multidrug resistance-associated protein 3 (MRP3), an efflux transporter on the hepatic basolateral membrane, may function as a compensatory mechanism to prevent the accumulation of anionic substrates (e.g., bile acids) in hepatocytes. Inhibition of MRP3 may disrupt bile acid homeostasis and is one hypothesized risk factor for the development of drug-induced liver injury (DILI). Therefore, identifying potential MRP3 inhibitors could help mitigate the occurrence of DILI. METHODS: Bayesian models were developed using MRP3 transporter inhibition data for 86 structurally diverse drugs...
May 30, 2017: European Journal of Pharmaceutical Sciences
Nasir Ahmad, Aqsa Farman, Syed Lal Badshah, Ata Ur Rahman, Haroon Ur Rashid, Khalid Khan
Ebola virus (EBOV) is a filamentous, enveloped, non-segmented, negative-strand ribonucleic acid (RNA) virus which belongs to family Filoviridae. Ebola virus includes different glycoproteins each of which plays their roles in different aspects of viral life cycle. In this study secreted glycoprotein (Q7T9E0) of Ebola virus was acquired from Uniprot. The formation of alpha helix and beta sheets of secondary structures were predicted through online servers. Higher flexibility and disordered regions of proteins were determined through RONN, GLOBPLOT and DISSEMBLE...
March 2017: Journal of Molecular Graphics & Modelling
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