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Fahima Syeda, Andrew P Holmes, Ting Y Yu, Samantha Tull, Stefan Michael Kuhlmann, Davor Pavlovic, Daniel Betney, Genna Riley, Jan P Kucera, Florian Jousset, Joris R de Groot, Stephan Rohr, Nigel A Brown, Larissa Fabritz, Paulus Kirchhof
BACKGROUND: Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). OBJECTIVES: After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs...
October 25, 2016: Journal of the American College of Cardiology
Sahan P Semasinghe Bandaralage, Selvanayagam Nirthanan, Selvanayagam Niranjan
Despite proven effectiveness in treating tachyarrhythmias, sotalol is proarrhythmic and can cause torsades de pointes. Given the emergence of studies that show no benefit from rhythm control strategies in managing atrial fibrillation, as well as the introduction of nonpharmacological approaches to treating arrhythmias, we felt it necessary to ascertain if there was any role for sotalol given its side effects. Review of the literature regarding sotalol use in the prevention and treatment of supraventricular and ventricular tachyarrhythmias seems to show that more effective and safer agents and nonpharmacological alternatives are currently available...
October 3, 2016: American Journal of Therapeutics
Tomomichi Ishizaka, Yu Yoshimatsu, Yu Maeda, Wataru Takasaki, Katsuyoshi Chiba, Kazuhiko Mori
INTRODUCTION: Load-independent cardiac parameters obtained from the ventricular pressure-volume relationship are recognized as gold standard indexes for evaluating cardiac inotropy.In this study, for better analyses of cardiac risks, load-independent pressure-volume loop parameters were assessed in addition to load-dependent inotropic, hemodynamic and electrocardiographic changes in isoflurane-anesthetized monkeys. METHODS: The animals were given milrinone (a PDE 3 inhibitor), metoprolol (a β-blocker), or dl-sotalol (a β+IKr blocker) intravenously over 10min at two dose levels including clinically relevant doses (n=5/drug)...
October 15, 2016: Journal of Pharmacological and Toxicological Methods
Kalle J Kaapu, Teemu J Murtola, Kirsi Talala, Kimmo Taari, Teuvo Lj Tammela, Anssi Auvinen
BACKGROUND: Protective effects have been suggested for digoxin against prostate cancer risk. However, few studies have evaluated the possible effects on prostate cancer-specific survival. We studied the association between use of digoxin or beta-blocker sotalol and prostate cancer-specific survival as compared with users of other antiarrhythmic drugs in a retrospective cohort study. METHODS: Our study population consisted of 6537 prostate cancer cases from the Finnish Randomized Study of Screening for Prostate Cancer diagnosed during 1996-2009 (485 digoxin users)...
October 18, 2016: British Journal of Cancer
Brit Long, Alex Koyfman
BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation are the causes of approximately 300,000 deaths per year in the United States. VT is classified based on hemodynamic status and appearance. Stable, monomorphic VT treatment is controversial. OBJECTIVE: Our aim was to provide emergency physicians with an evidence-based review of the medical management of stable, monomorphic VT. DISCUSSION: Stable, monomorphic VT is part of a larger class of ventricular dysrhythmias defined by a rate of at least 120 beats/min with QRS > 120 ms without regularly occurring P:QRS association...
October 14, 2016: Journal of Emergency Medicine
Daniele Muser, Pasquale Santangeli, Simon A Castro, Rajeev K Pathak, Jackson J Liang, Tatsuya Hayashi, Silvia Magnani, Fermin C Garcia, Mathew D Hutchinson, Gregory G Supple, David S Frankel, Michael P Riley, David Lin, Robert D Schaller, Sanjay Dixit, Erica S Zado, David J Callans, Francis E Marchlinski
BACKGROUND: Catheter ablation (CA) of ventricular tachycardia (VT) in patients with nonischemic dilated cardiomyopathy can be challenging because of the complexity of underlying substrates. We sought to determine the long-term outcomes of endocardial and adjuvant epicardial CA in nonischemic dilated cardiomyopathy. METHODS AND RESULTS: We examined 282 consecutive patients (aged 59±15 years, 80% males) with nonischemic dilated cardiomyopathy who underwent CA. Ablation was guided by activation/entrainment mapping for tolerated VT and pacemapping/targeting of abnormal electrograms for unmappable VT...
October 2016: Circulation. Arrhythmia and Electrophysiology
Mia Sivén, Satu Kovanen, Outi Siirola, Tuomas Hepojoki, Sari Isokirmo, Niina Laihanen, Tiina Eränen, Jukka Pellinen, Anne M Juppo
OBJECTIVES: The study evaluated the quality of compounded sachets and hard gelatine capsules and their feasibility in paediatric drug administration. METHODS: Commercial tablets were compounded to sachets and capsules in hospital environment, and the uniformity of content and simulated drug dose were determined. KEY FINDINGS: Compounded formulations were successfully obtained for a range of drug substances; dipyridamole, spironolactone, warfarin and sotalol formulations were within acceptable limits for uniformity of content, in most cases...
October 5, 2016: Journal of Pharmacy and Pharmacology
A T Chen, S Zou
Arrhythmia caused by drug-induced cardiotoxicity is among the leading reasons for late-stage drug attrition and is therefore a core subject in safety testing of new compounds. Alternative methods such as surface and interface characterization approaches for assessing the drug-mediated cardiotoxicity should be promoted, in order to reduce, refine and replace the use of laboratory animals. Here, we investigate the possibility of using known human Ether-à-go-go-Related Gene (hERG) channel blockers to induce irregular beating patterns in the mouse and human induced pluripotent stem cell-derived (miPSC and hiPSC) cardiomyocyte (CM) model systems...
September 29, 2016: Analyst
Frank Leresche, Urs von Gunten, Silvio Canonica
Dissolved organic matter (DOM) can act as a photosensitizer and an inhibitor in the phototransformation of several nitrogen-containing organic contaminants in surface waters. The present study was performed to select a probe molecule that is suitable to measure these antagonistic properties of DOM. Out of nine studied nitrogen-containing aromatic compounds, 4-cyanoaniline, N,N-dimethyl-4-cyanoaniline (DMABN), sotalol (a β-blocker) and sulfadiazine (a sulfonamide antibiotic) exhibited a marked photosensitized transformation that could be substantially inhibited by addition of phenol as a model antioxidant...
October 6, 2016: Environmental Science & Technology
V F S Dubois, G Smania, H Yu, R Graf, A Chain, M Danhof, O Della Pasqua
AIM: Despite screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of pro-arrhythmic activity using a comprehensive in vitro pro-arrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. Here we evaluate the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. METHODS: Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of 9 compounds with varying QT prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymised NCEs) were analysed...
September 10, 2016: British Journal of Clinical Pharmacology
David J Milan, J Philip Saul, John C Somberg, Janos Molnar
OBJECTIVES: The role of sotalol is well established for the maintenance of sinus rhythm after successful conversion of atrial fibrillation (AF). However, its role in pharmacologic conversion of AF is poorly defined. The purpose of this study is to compare the efficacy of sotalol to that of other antiarrhythmic agents for AF conversion. METHODS: Standard methods of meta-analysis were employed. Full-text publications of clinical trials in English that compared the efficacy of sotalol to that of other antiarrhythmics or placebo/no treatment were eligible for inclusion...
August 24, 2016: Cardiology
Chuixiu Huang, Knut Fredrik Seip, Astrid Gjelstad, Stig Pedersen-Bjergaard
Electromembrane extraction (EME) of polar basic drugs from human plasma was investigated for the first time using pure bis(2-ethylhexyl) phosphite (DEHPi) as the supported liquid membrane (SLM). The polar basic drugs metaraminol, benzamidine, sotalol, phenylpropanolamine, ephedrine, and trimethoprim were selected as model analytes, and were extracted from 300 μL of human plasma, through 10 μL of DEHPi as SLM, and into 100 μL of 10 mM formic acid as acceptor solution. The extraction potential across the SLM was 100 V, and extractions were performed for 20 min...
August 31, 2016: Analytica Chimica Acta
Jacques Rizkallah, Vikas Kuriachan, L Brent Mitchell
BACKGROUND: Dronedarone is a benzofuran derivative resembling amiodarone that was intended to reduce the iodine-associated tissue deposition and organ toxicity seen with the latter. The utility of dronedarone for patients with ventricular arrhythmias has not been thoroughly evaluated. We present our experience with its use to treat refractory ventricular tachycardia storm and review the literature. CASE PRESENTATION: An 85 year-old gentleman with multiple medical comorbidities including ischemic and non-ischemic cardiomyopathy with severe biventricular systolic dysfunction presented with ventricular tachycardia storm...
2016: BMC Research Notes
Patricia N Banfor, Gary A Gintant, John M Lipari, Philip D Zocharski
Screening novel, poorly soluble small-molecule candidates for cardiovascular liabilities represents a key challenge in early drug discovery. This report describes a novel vehicle composed of 20% N,N-Dimethylacetamide (DMA)/40% Propylene glycol (PG)/40% Polyethylene Glycol (PEG-400) (DPP) for administration of new chemical entities (NCEs) by slow intravenous (i.v.) infusion in a preclinical anesthetized rat model. The vehicle was designed considering both available excipient safety information and solubilization potential for poorly soluble NCEs...
July 16, 2016: Journal of Pharmacological and Toxicological Methods
V F S Dubois, E Casarotto, M Danhof, O Della Pasqua
BACKGROUND AND PURPOSE: Functional measures of human ether-à-go-go-related gene (hERG; Kv 11.1) channel inhibition have been prioritized as an in vitro screening tool for candidate molecules. However, it is unclear how these results can be translated to humans. Here, we explore how data on drug binding and functional inhibition in vitro relate to QT prolongation in vivo. Using cisapride, sotalol and moxifloxacin as paradigm compounds, we assessed the relationship between drug concentrations, binding, functional measures and in vivo effects in preclinical species and humans...
October 2016: British Journal of Pharmacology
Carl Hayward, Hitesh C Patel, Ketna Patel, Carlo Di Mario, Alexander R Lyon, Syed Y Ahsan, Edward Rowland
AIMS: An important decision in the management of patients with atrial fibrillation is whether to adopt a rate or rhythm control strategy. Options for the latter include oral membrane-active anti-arrhythmic drugs (AADs) or catheter ablation. Recent prescription trends may have been affected by the introduction of dronedarone and an increasing number of reports suggesting increased mortality in those taking AADs. We describe the trend in oral AAD prescriptions in England in the period 1998-2014...
April 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Yishen Wang, Shamsher Singh, Beata Bajorek
BACKGROUND: The safety of pharmacotherapy in atrial fibrillation (AF) is compounded by a trilogy of risks old age, high-risk medications (e.g., antithrombotics, antiarrhythmics), polypharmacy due to multiple patient comorbidities. However, to date, scarce study has investigated the use of polypharmacy (including potentially inappropriate medication (PIM)) in AF patients, and how this may contribute to their overall risk of medication misadventure. OBJECTIVES: To review the extent of polypharmacy and PIM use in older patients (65 years or older) with AF...
April 2016: Pharmacy Practice
N Paxéus, K Bester, Haitham El-taliawy
Loads of individual commonly used analgesics (ibuprofen, diclofenac), antibiotics (sulfamethoxazole, trimethoprim), β-blockers (atenolol, metoprolol, sotalol, propranolol) and neuroleptics (carbamazepine, citalopram) to a large-scale operating wastewater treatment plant (WWTP) in Sweden (Ryaverket) were studied by monitoring concentrations and flows during a 9-year period (2006-2015). Variations in loads due to sampling and possible errors in chemical analyses were estimated to be below 40%. The variations in loads were analyzed and discussed in terms of the design of collecting wastewater system as an integrated part of the water treatment at the WWTP as well as the prescription and use of individual pharmaceuticals...
2016: Water Science and Technology: a Journal of the International Association on Water Pollution Research
Natasha A Kassim, Andrew D Althouse, Dingxin Qin, George Leef, Samir Saba
BACKGROUND: Prior research has identified gender differences in the epidemiology and clinical management of atrial fibrillation (AF). The primary aim of this study is to systematically analyze a cohort of AF men and women and evaluate their baseline demographics, treatment, and clinical outcomes by gender. METHODS: We examined the records of 5976 (42% women) consecutive AF patients who were prescribed at least one anti-arrhythmic drug between 2006 and 2013. From this cohort, 4311 (72%) patients had anticoagulation data available and were included in the final analysis...
June 1, 2016: Journal of Cardiology
John Alvin Kpaeyeh, John Marcus Wharton
Sotalol is effective for treating atrial fibrillation (AF), ventricular tachycardia, premature ventricular contractions, and supraventricular tachycardia. Racemic (DL) sotalol inhibits the rapid component of the delayed rectifier potassium current. There is a near linear relationship between sotalol dosage and QT interval prolongation. However, in dose ranging trials in patients with AF, low-dose sotalol was not more effective than placebo. Orally administered sotalol has a bioavailability of nearly 100%. The only significant drug interactions are the need to avoid or limit use of concomitant drugs that cause QT prolongation, bradycardia, and/or hypotension...
June 2016: Cardiac Electrophysiology Clinics
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