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https://www.readbyqxmd.com/read/28527921/drug-induced-fatal-arrhythmias-acquired-long-qt-and-brugada-syndromes
#1
REVIEW
Isik Turker, Tomohiko Ai, Hideki Itoh, Minoru Horie
Since the early 1990s, the concept of primary "inherited" arrhythmia syndromes or ion channelopathies has evolved rapidly as a result of revolutionary progresses made in molecular genetics. Alterations in genes coding for membrane proteins such as ion channels or their associated proteins responsible for the generation of cardiac action potentials (AP) have been shown to cause specific malfunctions which eventually lead to cardiac arrhythmias. These arrhythmic disorders include congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, progressive cardiac conduction disease, etc...
May 17, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28525371/arsenic-trioxide-and-angiotensin-ii-have-inhibitory-effects-on-herg-protein-expression-evidence-for-the-role-of-pml-sumoylation
#2
Yu Liu, Duo Li, Dan Nie, Shang-Kun Liu, Fang Qiu, Mei-Tong Liu, Yuan-Yuan Li, Jia-Xin Wang, Yan-Xin Liu, Chang-Jiang Dong, Di Wu, Wei Tian, Jia Yang, Wei Mu, Jia-Tong Li, Dan Zhao, Xiao-Feng Wang, Wen-Feng Chu, Bao-Feng Yang
The human ether-a-go-go-related gene (HERG) channel is a novel target for the treatment of drug-induced long QT syndrome, which causes lethal cardiotoxicity. This study is designed to explore the possible role of PML SUMOylation and its associated nuclear bodies (NBs) in the regulation of HERG protein expression. Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Pre-exposure of cardiomyocytes to a SUMOylation chemical inhibitor, ginkgolic acid, or the silencing of UBC9 suppressed PML SUMOylation, subsequently preventing the downregulation of HERG induced by ATO or Ang II...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522677/synergistic-effect-of-dofetilide-and-mexiletine-on-prevention-of-atrial-fibrillation
#3
Guizhi Liu, Xiaolin Xue, Chuanyu Gao, Jiaqi Huang, Datun Qi, Yanzhou Zhang, Jian-Zeng Dong, Chang-Sheng Ma, Gan-Xin Yan
BACKGROUND: Although atrial fibrillation (AF) is the most common abnormal heart rhythm and its prevalence continues to rise, there is a marked paucity of effective and safe antiarrhythmic drugs for AF. This study was done to test whether combined use of dofetilide and mexiletine exhibits not only a synergistic effect on AF suppression but also a safer profile in drug-induced ventricular proarrhythmias. METHODS AND RESULTS: The effects of dofetilide plus mexiletine on atrial effective refractory period (ERP), AF inducibility, QT, and QT-related ventricular arrhythmias were studied using the isolated arterially perfused rabbit atrial and ventricular wedge preparations...
May 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28521790/unintentional-drowning-role-of-medicinal-drugs-and-alcohol
#4
Tuulia Pajunen, Erkki Vuori, Frank F Vincenzi, Pirjo Lillsunde, Gordon Smith, Philippe Lunetta
BACKGROUND: Alcohol is a well-known risk factor in unintentional drownings. Whereas psychotropic drugs, like alcohol, may cause psychomotor impairment and affect cognition, no detailed studies have focused on their association with drowning. Finland provides extensive post-mortem toxicological data for studies on drowning because of its high medico-legal autopsy rates. METHODS: Drowning cases, 2000 through 2009, for which post-mortem toxicological analysis was performed, came from the database of the Toxicological Laboratory, Department of Forensic Medicine, University of Helsinki, using the ICD-10 nature-of-injury code T75...
May 19, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28521025/mechanism-of-as2o3-induced-action-potential-prolongation-and-using-hips-cms-to-evaluate-the-rescue-efficacy-of-drugs-with-different-rescue-mechanism
#5
Meng Yan, Lifang Feng, Yanhui Shi, Junnan Wang, Yan Liu, Fengmei Li, Baoxin Li
Arsenic trioxide (As2O3) has been verified as a breakthrough in the management of acute promyelocytic leukemia in recent decades. However, cardiotoxicity, especially long QT syndrome (LQTS) has become the most important issue during As2O3 treatment. The characterized mechanisms behind this adverse effect are inhibition of cardiac hERG channel trafficking and increase of cardiac calcium currents. In our study, we found a new pathway underlying As2O3-induced cardiotoxicity that As2O3 accelerates lysosomal degradation of hERG on plasma membrane after using brefeldin A (BFA) to block protein trafficking...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28511997/thorough-qt-tqt-studies-concordance-with-torsadogenesis-and-an-evolving-cardiac-safety-testing-paradigm
#6
Barbara Wiśniowska, Zofia Tylutki, Sebastian Polak
Since 2005, when the International Conference on Harmonisation (ICH) E14 guideline was adopted, no drug has been withdrawn because of QTc prolongation or torsade de pointes arrhythmia. There are, however, costs associated with this success. In addition to the time and money invested, thorough QT (TQT) studies have limited the efficiency of the drug development pipeline. In this paper, we discuss the relevance of TQT trials as a tool for proarrhythmic risk prediction as a part of the debate regarding their usefulness...
May 13, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28510647/epicardial-cardioverter-defibrillator-implantation-in-a-4-month-old-infant-bridged-to-heart-transplantation
#7
Cristina Carro, Alberto Francesco Cereda, Giuseppe Annoni, Stefano Maria Marianeschi
Implantable cardioverter-defibrillator (ICD) is the gold standard therapy for the prevention of sudden cardiac death. Nevertheless, ICD placement in the paediatric population is still limited because of several technical difficulties. Several implantation techniques have been proposed but experience in infants with very low weight and less than 6 months is very limited. We herein describe a case of a minimally invasive ICD epicardial implantation in a 4-month-old infant weighing 5 kg. A diagnosis of arrhythmic cardiomyopathy with left ventricular non-compaction disease with ventricular tachycardia storms, QT prolongation and Wolff-Parkinson-White pattern was made...
May 16, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28506854/long-term-safety-and-efficacy-of-solifenacin-in-children-and-adolescents-with-overactive-bladder
#8
Donald Newgreen, Brigitte Bosman, Adriana Hollestein-Havelaar, Ellen Dahler, Robin Besuyen, Robert Snijder, Will Sawyer, Søren Rittig, Stéphane Bolduc
PURPOSE: To evaluate long-term safety and efficacy of once-daily oral solifenacin suspension in children (aged 5-<12 years) and adolescents (aged 12-<18 years) with overactive bladder. MATERIALS AND METHODS: 40-week, open-label extension of a 12-week double-blind, placebo-controlled trial. OUTCOME MEASURES: incidence and severity of adverse events (primary endpoint), laboratory variables, vital signs, 12-lead electrocardiogram, post-void residual volume, change from baseline to end of treatment in: mean number of micturitions and incontinence episodes/24 hours, number of incontinence-free days/7 days, number of grade 3 or 4 urgency episodes/24 hours (adolescents only)...
May 12, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28506844/proarrhythmic-risk-assessment-using-conventional-and-new-in%C3%A2-vitro-assays
#9
Sonia Goineau, Vincent Castagné
Drug-induced QT prolongation is a major safety issue in the drug discovery process. This study was conducted to assess the electrophysiological responses of four substances using established preclinical assays usually used in regulatory studies (hERG channel or Purkinje fiber action potential) and a new assay (human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)-field potential). After acute exposure, moxifloxacin and dofetilide concentration-dependently decreased IKr amplitude (IC50 values: 102 μM and 40 nM, respectively) and lengthened action potential (100 μM moxifloxacin: +23% and 10 nM dofetilide: +18%) and field potential (300 μM moxifloxacin: +76% and 10 nM dofetilide: +38%) durations...
May 12, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28506500/autonomic-and-electrocardiographic-findings-in-parkinson-s-disease
#10
Christopher H Gibbons, David K Simon, Meilin Huang, Barbara Tilley, Michael J Aminoff, Jacquelyn L Bainbridge, Matthew Brodsky, Roy Freeman, John Goudreau, Robert W Hamill, Sheng T Luo, Carlos Singer, Aleksandar Videnovic, Ivan Bodis-Wollner, Pei S Wong
Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and signs. Many reports suggest that diminished heart rate variability occurs early, even prior to the cardinal signs of PD. In a longitudinal study of PD, we evaluated whether heart rate variability (HRV) obtained using a 10-second ECG tracing, and the electrocardiographic QT-interval would be associated with PD severity and progression. Subjects were derived from a longitudinal study of 1741 individuals with early, stable PD...
April 14, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28501647/application-of-optical-action-potentials-in-human-induced-pluripotent-stem-cells-derived-cardiomyocytes-to-predict-drug-induced-cardiac-arrhythmias
#11
H R Lu, M P Hortigon-Vinagre, V Zamora, I Kopljar, A De Bondt, D J Gallacher, G Smith
INTRODUCTION: Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay. METHODS: Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds...
May 10, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28499268/first-universal-pharmacophore-model-for-herg1-k-channel-activators-acther
#12
Serdar Durdagi, Ismail Erol, Ramin Ekhteiari Salmas, Matthew Patterson, Sergei Y Noskov
The intra-cavitary drug blockade of hERG1 channel has been extensively studied, both experimentally and theoretically. Structurally diverse ligands inadvertently block the hERG1 K(+) channel currents lead to drug induced Long QT Syndrome (LQTS). Accordingly, designing either hERG1 channel openers or current activators, with the potential to target other binding pockets of the channel, has been introduced as a viable approach in modern anti-arrhythmia drug development. However, reports and investigations on the molecular mechanisms underlying activators binding to the hERG1 channel remain sparse and the overall molecular design principles are largely unknown...
April 5, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28497864/valbenazine-for-tardive-dyskinesia-a-systematic-review-of-the-efficacy-and-safety-profile-for-this-newly-approved-novel-medication-what-is-the-number-needed-to-treat-number-needed-to-harm-and-likelihood-to-be-helped-or-harmed
#13
REVIEW
Leslie Citrome
OBJECTIVE: The objective of this systematic review was to describe the efficacy, tolerability, and safety of valbenazine for the treatment of tardive dyskinesia (TD). DATA SOURCES: The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the search terms 'valbenazine' OR 'NBI-98854', and by also querying the EMBASE (Elsevier) commercial database for clinical poster abstracts, and by asking the manufacturer for copies of posters presented at congresses...
May 12, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28496937/amiodarone-induced-third-degree-atrioventricular-block-and-extreme-qt-prolongation-generating-torsade-des-pointes-in-paroxysmal-atrial-fibrillation
#14
Orlando Robert Sequeira, Nelson Javier Aquino, Nancy Beatriz Gómez, Laura Beatriz García, Cristina Cáceres, Oscar A Lovera, Osmar Antonio Centurión
Amiodarone is still the most potent antiarrhythmic drug in the prevention of life threatening ventricular arrhythmias and demonstrates a very low incidence of torsade de pointes. An unusual case of an 81-year-old woman who developed serious abnormalities of the conduction system of the heart and torsade des pointes during intravenous infusion of amiodarone for the treatment of paroxysmal atrial fibrillation is described. To the best of our knowledge, this is the first case showing an association of intravenous amiodarone-induced third degree atrioventricular block and extreme QT interval prolongation generating torsade des pointes in a patient with paroxysmal atrial fibrillation who required an implantable cardioverter-defibrillator...
October 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/28495999/%C3%AE-arrestin-mediated-regulation-of-the-human-ether-a-go-go-related-gene-herg-potassium-channel
#15
Matthew G Sangoi, Shawn M Lamothe, Jun Guo, Tonghua Yang, Wentao Li, Ellen G Avery, John T Fisher, Shetuan Zhang
The rapidly activating delayed rectifier K(+) channel (IKr) is encoded by the human ether-a-go-go-related gene (hERG), which is important for the repolarization of the cardiac action potential. Mutations in hERG or drugs can impair the function or decrease the expression level of hERG channels, leading to long QT syndrome (LQTS). Thus, it is important to understand hERG channel trafficking and its regulation. For this purpose, G protein-coupled receptors (GPCRs), which regulate a vast array of cellular processes, represent a useful route...
May 11, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28495651/percentile-categorization-of-qt-interval-as-an-approach-for-identifying-adult-patients-at-risk-for-cardiovascular-death
#16
Reza Mohebi, Ayesha Jehan, Aaron Grober, Victor Froelicher
BACKGROUND: The results from studies of the association of QT prolongation with CVD have been inconsistent. OBJECTIVES: To compare the major correction formulas to percentile values of QT for heart rate ranges as to their ability to remove the relationship of QT to heart rate and to predict cardiovascular death(CVD). METHODS: Participants were 16,531 veterans who had an initial ECG at the Veterans Affairs Medical Center, Palo Alto between March 31, 1987, and December 20, 1999 and were followed for CVD...
May 8, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28494415/studies-on-curative-efficacy-of-monoterpene-eugenol-on-anti-leukemic-drug-arsenic-trioxide-induced-cardiotoxicity
#17
Prakash Binu, Nellikunnath Priya, Surendran Abhilash, Radhakrishnan Chandraprabha Vineetha, Raveendran Harikumaran Nair
BACKGROUND: Arsenic trioxide (As2O3) is emerging as a frontline agent for the treatment of acute promyelocytic leukemia (APL) but the therapeutic application is limited by its toxicity. QT prolongation, torsades de pointes and sudden cardiac death have been implicated in the As2O3 therapy. So eugenol is a monoterpene compound is well known for its antioxidant properties and protective effect on the cardiovascular system. OBJECTIVE: In this study, the cardioprotective effect of eugenol on cardiac electrical conductivity, tissue electrolytes, myocardial markers, antioxidant system, lipid peroxidation and nitric oxide production was investigated in male Wistar rats treated with arsenic trioxide...
May 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28488108/-ventricular-tachyarrhythmia-as-a-side-effect-of-pharmacotherapy
#18
REVIEW
Thomas Demming, Hendrik Bonnemeier
Ventricular tachyarrhythmia is a severe and life-threatening potential side effect of pharmacotherapy. Substances with proarrhythmic potential belong to various groups of medication. Apart from antiarrhythmic agents, especially antibiotics and psychiatric drugs are worth mentioning owing to their broad application. Interaction with cardiac potassium channels is the most important reason for drug-induced ventricular tachyarrhythmia. Over 20 years of research in animal models and clinical studies have uncovered the underlying mechanisms...
May 9, 2017: Herzschrittmachertherapie & Elektrophysiologie
https://www.readbyqxmd.com/read/28486375/domperidone-for-lactation-what-health-care-providers-need-to-know
#19
Catherine A Sewell, Christina Y Chang, Miriam M Chehab, Christine P Nguyen
This commentary serves to raise health care provider awareness about the regulatory status and available evidence regarding domperidone for insufficient lactation. Breastfeeding provides significant health benefits for mothers and infants, and insufficient milk production remains the most common reason for early weaning. Domperidone, a dopamine receptor antagonist that may increase milk production, is not approved for any human use in the United States. It is approved in some countries for certain gastrointestinal disorders, but is not approved in any country for lactation enhancement...
June 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28480041/risk-of-qt-prolongation-and-torsade-de-pointes-associated-with-exposure-to-hydroxyzine-re-evaluation-of-an-established-drug
#20
Anne-Françoise Schlit, Annie Delaunois, Aurore Colomar, Branderley Claudio, Luca Cariolato, Rossen Boev, Jean-Pierre Valentin, Christopher Peters, Victor S Sloan, Jürgen W G Bentz
Several noncardiac drugs have been linked to cardiac safety concerns, highlighting the importance of post-marketing surveillance and continued evaluation of the benefit-risk of long-established drugs. Here, we examine the risk of QT prolongation and/or torsade de pointes (TdP) associated with the use of hydroxyzine, a first generation sedating antihistamine. We have used a combined methodological approach to re-evaluate the cardiac safety profile of hydroxyzine, including: (1) a full review of the sponsor pharmacovigilance safety database to examine real-world data on the risk of QT prolongation and/or TdP associated with hydroxyzine use and (2) nonclinical electrophysiological studies to examine concentration-dependent effects of hydroxyzine on a range of human cardiac ion channels...
June 2017: Pharmacology Research & Perspectives
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