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https://www.readbyqxmd.com/read/27920831/assessment-of-drug-induced-proarrhythmias-due-to-pilsicainide-in-patients-with-atrial-tachyarrhythmias
#1
Hideki Koike, Tadashi Fujino, Makiko Koike, Shintaro Yao, Masaya Shinohara, Ken Kitahara, Toshio Kinoshita, Hitomi Yuzawa, Takeya Suzuki, Hideyuki Sato, Shunji Fukunaga, Kenzaburo Kobayashi, Takanori Ikeda
BACKGROUND: Pilsicainide, a pure Na(+) channel blocker, is a popular antiarrhythmic drug for the management of atrial tachyarrhythmias (AT), in Japan. However, serious drug-induced proarrhythmias (DIPs) may unexpectedly occur. We assessed the clinical background of AT patients presenting with DIPs caused by pilsicainide. METHODS: This study retrospectively enrolled 874 consecutive patients (543 men, 63.6±15.3 years old, and 57.9±16.5 kg of body weight), who were orally administered pilsicainide for AT management...
December 2016: Journal of Arrhythmia
https://www.readbyqxmd.com/read/27917367/the-role-of-interaction-model-in-simulation-of-drug-interactions-and-qt-prolongation
#2
REVIEW
Barbara Wiśniowska, Sebastian Polak
Computational modelling is a cornerstone of Comprehensive In Vitro Proarrhythmia Assay and is re-increasingly being used in drug development. Electrophysiological effects of drug-drug interactions can be predicted in silico, e.g. with the use of in vitro cardiac ion channel data, PK profiles and human ventricular cardiomyocyte models. There are, however, several approaches with different assumptions used to assess the combined effect of multiple drugs, and there is no agreed standard interaction model. The aim of this study was to assess whether the choice of the drug-drug interaction (DDI) model (Bliss independence, Loewe additivity, or simple sum) influences the results of QT interval simulation trial...
2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/27899938/detailed-analysis-of-the-impact-of-age-on-the-qt-interval
#3
Simon W Rabkin, Xin-Bo Justin Cheng, Darby Js Thompson
OBJECTIVE: To analyze the effect of age on the ECG QT interval, an important predictor of cardiovascular mortality and drug-induced cardiac arrhythmias, and determine whether QT-heart rate correction formulae (QTc) have differential relationships with age and sex. METHODS: Data were examined from the US National Health and Nutrition Examination Survey (NHANES) II and III, civilian population aged 25 to 90 years. QT weighted means and standard deviations were calculated for all ages...
September 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/27899087/paradoxical-physiological-responses-to-propranolol-in-a-rett-syndrome-patient-a-case-report
#4
P J Santosh, L Bell, K Lievesley, J Singh, F Fiori
BACKGROUND: Rett Syndrome (RTT), caused by a loss-of-function in the epigenetic modulator: X-linked methyl-CpG binding protein 2 (MeCP2), is a pervasive neurological disorder characterized by compromised brain functions, anxiety, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. An imbalance in the sympathetic and the parasympathetic nervous system (dysautonomia) and the resulting autonomic storms is a frequent occurrence in patients with RTT...
November 29, 2016: BMC Pediatrics
https://www.readbyqxmd.com/read/27894750/risk-factors-for-autonomic-and-somatic-nerve-dysfunction-in-different-stages-of-glucose-tolerance
#5
Rumyana Dimova, Tsvetalina Tankova, Velina Guergueltcheva, Ivailo Tournev, Nevena Chakarova, Greta Grozeva, Lilia Dakovska
AIM: The present study evaluates autonomic and somatic nerve function in different stages of glucose tolerance and its correlation with different cardio-metabolic parameters. MATERIAL AND METHODS: Four hundred seventy-eight subjects, mean age 49.3±13.7years and mean BMI 31.0±6.2kg/m2, divided according to glucose tolerance: 130 with normal glucose tolerance (NGT), 227 with prediabetes (125 with impaired fasting glucose (IFG) and 102 with isolated impaired glucose tolerance (iIGT)), and 121 with newly-diagnosed T2D (NDT2D), were enrolled...
November 6, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27893184/ecg-alterations-associated-with-psychotropic-drug-use-and-cacna1c-gene-variants-in-three-independent-samples
#6
Chiara Fabbri, Giuseppe Boriani, Igor Diemberger, Maria Giulia Filippi, Gloria Ravegnini, Patrizia Hrelia, Alessandro Minarini, Diego Albani, Gianluigi Forloni, Sabrina Angelini, Alessandro Serretti
Several antipsychotics and antidepressants have been associated with QTc prolongation or other ECG alterations, but their impact is still debated and other risk factors are known to affect QTc. We investigated the effect of antidepressants and antipsychotics on QTc and other ECG intervals/waves in three samples. Two discovery samples (cross-sectional sample n=145 and prospective sample n=68, naturalistic treatment) and a replication prospective sample (CATIE, n=515, randomized treatment) were analysed. In both prospective samples, baseline/follow-up changes in ECG parameters were analysed in relation to the number of psychotropic drugs stratified according to their known cardiovascular risk...
November 28, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27886373/clemizole-hydrochloride-blocks-cardiac-potassium-currents-stably-expressed-in-hek-293-cells
#7
Ling-Jun Jie, Wei-Yin Wu, Gang Li, Guo-Sheng Xiao, Shetuan Zhang, Gui-Rong Li, Yan Wang
BACKGROUND AND PURPOSE: Recent studies showed that clemizole has a potential therapeutic effect for hepatitis C infection and also potently inhibits TRPC5 channels. The aim of the present study was to investigate whether clemizole blocks cardiac K(+) currents and affects cardiac repolarization. EXPERIMENTAL APPROACH: Whole-cell patch technique was employed to examine the effects of clemizole on hERG channel current, IKs and Kv1.5 current in HEK 293 cell expression systems as well as on ventricular action potentials of guinea pig hearts...
November 25, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27882731/reproducibility-of-corrected-qt-interval-in-pediatric-genotyped-long-qt-syndrome
#8
Yoshiharu Ogawa, Toshikatsu Tanaka, Sachiko Kido
Reproducibility of corrected QT interval (QTc), especially QTc after exercise, has not been thoroughly investigated. We reviewed charts of pediatric patients who underwent treadmill-exercise stress testing without medication multiple times within 1 year. In patients with long-QT syndrome (LQTS; n = 22), the discrepancy in QTc between two treadmill exercise stress tests using Fridericia's formula was 14 ± 12 ms at rest, 13 ± 12 ms 4 min after exercise, with a maximum of 14 ± 12 ms after exercise. There was no statistically significant difference in QTc between the two tests...
November 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/27875900/effects-of-necrostatin-1-an-inhibitor-of-necroptosis-and-its-inactive-analogue-nec-1i-on-basal-cardiovascular-function
#9
A Szobi, T Rajtik, A Adameova
Inhibition of receptor-interacting serine/threonine-protein kinase 1 (RIP1) by necrostatin-1 (Nec-1) alleviates cardiac injury due to prevention of necroptotic cell death. Its inactive analogue necrostatin-1i (Nec-1i), lacking RIP1 activity, serves as a suitable control. It is unknown if these agents influence the heart function in the absence of damaging stimuli. For this purpose, we measured intraarterial blood pressure (systolic - sBP and diastolic - dBP) and ECG parameters after a bolus administration of Nec-1 and Nec-1i in rats during 30 min...
November 23, 2016: Physiological Research
https://www.readbyqxmd.com/read/27865890/safety-tolerability-and-efficacy-of-repeated-doses-of-dihydroartemisinin-piperaquine-for-prevention-and-treatment-of-malaria-a-systematic-review-and-meta-analysis
#10
Julie Gutman, Stephanie Kovacs, Grant Dorsey, Andy Stergachis, Feiko O Ter Kuile
BACKGROUND: Intermittent preventive treatment (IPT) for malaria is used in infants, children, adults, and pregnant women. Dihydroartemisinin-piperaquine (DP) is an effective, well tolerated artemisinin-based combination therapy. The long half-life of piperaquine makes it attractive for IPT. We conducted a systematic review and meta-analysis to establish the efficacy and safety of repeated treatment with DP. METHODS: Following PRISMA guidelines, we searched multiple databases on Sept 1, 2016, with the terms: "human" AND "dihydroartemisinin-piperaquine" OR "DHA-PPQ"...
November 16, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27864903/long-term-monitoring-of-cardiorespiratory-patterns-in-drug-resistant-epilepsy
#11
Daniel M Goldenholz, Amanda Kuhn, Alison Austermuehle, Martin Bachler, Christopher Mayer, Siegfried Wassertheurer, Sara K Inati, William H Theodore
OBJECTIVE: Sudden unexplained death in epilepsy (SUDEP) during inpatient electroencephalography (EEG) monitoring has been a rare but potentially preventable event, with associated cardiopulmonary markers. To date, no systematic evaluation of alarm settings for a continuous pulse oximeter (SpO2 ) has been performed. In addition, evaluation of the interrelationship between the ictal and interictal states for cardiopulmonary measures has not been reported. METHODS: Patients with epilepsy were monitored using video-EEG, SpO2 , and electrocardiography (ECG)...
November 16, 2016: Epilepsia
https://www.readbyqxmd.com/read/27864544/investigative-nonclinical-cardiovascular-safety-and-toxicology-studies-with-bms-986094-an-ns5b-rna-dependent-rna-polymerase-inhibitor
#12
M Gill, K Horn, J Hennan, R White, D Bounous, S Clark, J R Megill, E Janovitz, M Davies, T Sanderson, M Graziano
BMS-986094, a 2'-C-methylguanosine prodrug that was in development for treatment of chronic hepatitis C infection was withdrawn from Phase 2 clinical trials because of unexpected cardiac and renal adverse events. Investigative nonclinical studies were conducted to extend the understanding of these findings using more comprehensive endpoints. BMS-986094 was given orally to female CD-1 mice (25 and 150 mg/kg/d) for 2 weeks (53/group) and to cynomolgus monkeys (15 and 30 mg/kg/d) for up to 6 weeks (2-3/sex/group for cardiovascular safety, and 5/sex/group for toxicology)...
November 17, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27862484/%C3%AE-1-adrenoceptor-autoantibodies-increase-the-susceptibility-of-ventricular-arrhythmias-involving-abnormal-repolarization-in-guinea-pigs
#13
Yu-Hui Zhao, Hai-Xia Huang, Ping Liu, Yun-Hui Du, Peng Wang, Wen Wang, Ye Wu, Li Wang, Chang-Sheng Ma, Hui-Rong Liu
High titers of autoantibodies against the second extracellular loop of β1 -adrenergic receptors (β1 -AA) can be detected in the sera from patients with ventricular arrhythmias, but a causal relationship between β1 -AAs and ventricular arrhythmias has not been established. In this work, electrocardiograms of guinea pigs and isolated guinea pig hearts were recorded. Ventricular tachycardia (VT) and ventricular fibrillation (VF) were evoked by programmed electrical stimulation of the left ventricular epicardium of isolated guinea pig hearts...
November 11, 2016: Experimental Physiology
https://www.readbyqxmd.com/read/27850494/856-qtc-interval-prolongation-with-low-dose-iv-haloperidol-post-hoc-analysis-of-a-placebo-control-trial
#14
Matthew Duprey, Nada Al-Qadheeb, Russel Roberts, Yoanna Skrobik, Greg Schumaker, John Devlin
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27837002/safety-of-domperidone-in-treating-nausea-associated-with-dihydroergotamine-infusion-and-headache
#15
Nathaniel M Robbins, Hiroyuki Ito, Melvin M Scheinman, Peter J Goadsby
OBJECTIVE: To determine the safety of domperidone in the treatment of nausea associated with dihydroergotamine (DHE) infusion and headache. METHODS: We audited our use of domperidone for the inpatient management of nausea, focusing on known safety concerns, particularly potential cardiac arrhythmias. RESULTS: We reviewed 103 consecutive admissions of 90 patients admitted for IV DHE by infusion. Most admissions were to treat chronic migraine with (n = 53) or without (n = 46) aura...
November 11, 2016: Neurology
https://www.readbyqxmd.com/read/27835715/ziprasidone-augmentation-of-escitalopram-for-major-depressive-disorder-cardiac-endocrine-metabolic-and-motoric-effects-in-a-randomized-double-blind-placebo-controlled-study
#16
David Mischoulon, Richard C Shelton, Lee Baer, William V Bobo, Laura Curren, Maurizio Fava, George I Papakostas
OBJECTIVE: To examine motoric, cardiovascular, endocrine, and metabolic effects of adjunctive ziprasidone in adults with major depressive disorder (MDD) and prior nonresponse to 8 weeks of open-label escitalopram. METHODS: A multicenter, parallel, randomized, double-blind, placebo-controlled trial was conducted at 3 US academic medical centers from July 2008 to October 2013. Recruited were 139 outpatients with persistent DSM-IV MDD following an 8-week open-label trial of escitalopram...
November 8, 2016: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/27826183/supratherapeutic-dose-evaluation-and-effect-of-lesinurad-on-cardiac-repolarization-a-thorough-qt-qtc-study
#17
Zancong Shen, Michael Gillen, Kathy Tieu, Mai Nguyen, Erin Harmon, David M Wilson, Bradley Kerr, Caroline A Lee
INTRODUCTION: Lesinurad is a selective uric acid reabsorption inhibitor approved in the United States and Europe for treatment of gout in combination with a xanthine oxidase inhibitor. A maximum tolerated dose study was conducted to determine the lesinurad supratherapeutic dose, followed by a thorough QTc study to characterize the effect of lesinurad on cardiac repolarization. METHODS: The maximum tolerated dose study was a randomized, double-blind, placebo-controlled, single-ascending dose study that enrolled 35 healthy men and women...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27823873/a-prospective-observational-study-of-patients-receiving-intravenous-and-intramuscular-olanzapine-in-the-emergency-department
#18
Jon B Cole, Johanna C Moore, Benjamin J Dolan, Alex O'Brien-Lambert, Brandon J Fryza, James R Miner, Marc L Martel
STUDY OBJECTIVE: Parenteral olanzapine is an emerging therapy for a variety of conditions in the emergency department (ED). Intramuscular administration is standard; however, intravenous administration has been proposed as a safe alternative route. We investigate the safety and efficacy of both intramuscular and intravenous olanzapine in the ED when used for a variety of indications. METHODS: This was a prospective observational study of patients presenting to an urban Level I trauma center ED...
November 4, 2016: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/27823869/intravenous-dosing-as-an-alternate-approach-to-safely-achieve-supratherapeutic-exposure-for-assessments-of-cardiac-repolarization-a-randomized-clinical-trial-with-mavoglurant-afq056
#19
Mike Ufer, Alexandros Sagkriotis, Atish Salunke, Subramanian Ganesan, Anne Tisserant, Angela Dodman, Emilie Voltz, Ralph Woessner, Pierre Jordaan, Eric Legangneux
PURPOSE: The conduct of thorough QTc (TQT) studies is often challenging with compounds that are characterized by limited tolerability in healthy individuals. This is applicable to several central nervous system drugs, including mavoglurant acting as a selective allosteric modulator of metabotropic glutamate receptor 5. This TQT study describes the use of a single intravenous dosing regimen as an alternate approach allowing for sufficiently high Cmax values while controlling tolerability...
November 4, 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27816319/contribution-of-a-kcnh2-variant-in-genotyped-long-qt-syndrome-romano-ward-syndrome-under-double-mutations-and-acquired-long-qt-syndrome-under-heterozygote
#20
Yusuke Fujii, Yuichi Matsumoto, Kenshi Hayashi, Wei-Guang Ding, Yukinori Tomita, Daisuke Fukumoto, Yuko Wada, Mari Ichikawa, Keiko Sonoda, Junichi Ozawa, Takeru Makiyama, Seiko Ohno, Masakazu Yamagishi, Hiroshi Matsuura, Minoru Horie, Hideki Itoh
BACKGROUND: Long QT syndrome (LQTS) presents two clinical phenotypes, congenital and acquired forms. This study aims to evaluate the genetic contribution of a KCNH2 variant for the two LQTS phenotypes. METHODS: From 1996 to 2014, genetic screening for LQTS probands was performed for five major genes: KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 and 389 probands were found to be mutation carriers. We analyzed the clinical phenotypes of p.His492Tyr carriers in KCNH2. RESULTS: Heterozygous p...
November 2, 2016: Journal of Cardiology
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