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drug induced ECG changes

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https://www.readbyqxmd.com/read/27560382/a-novel-scn5a-mutation-associated-with-drug-induced-brugada-type-ecg
#1
Isik Turker, Takeru Makiyama, Matteo Vatta, Hideki Itoh, Takeshi Ueyama, Akihiko Shimizu, Tomohiko Ai, Minoru Horie
BACKGROUND: Class IC antiarrhythmic agents may induce acquired forms of Brugada Syndrome. We have identified a novel mutation in SCN5A, the gene that encodes the α-subunit of the human cardiac sodium channel (hNav1.5), in a patient who exhibited Brugada- type ECG changes during pharmacotherapy of atrial arrhythmias. OBJECTIVE: To assess whether the novel mutation p.V1328M can cause drug induced Brugada Syndrome. METHODS: Administration of pilsicainide, a class IC antiarrhythmic agent, caused Brugada- type ST elevation in a 66-year-old Japanese male who presented with paroxysmal atrial fibrillation (PAF), type I atrial flutter and inducible ventricular fibrillation (VF) during electrophysiological study...
2016: PloS One
https://www.readbyqxmd.com/read/27509828/meperidine-induced-qtc-interval-prolongation-prevalence-risk-factors-and-correlation-to-plasma-drug-and-metabolite-concentrations%C3%A2
#2
Guillermo Alberto Keller, María Cecilia Villa Etchegoyen, Nicolás Fernández, Nancy Mónica Olivera, Patricia Noemí Quiroga, Roberto Alejandro Diez, Guillermo Di Girolamo
: A prolongation of the QTc-interval has been described for several opioids, including pethidine (meperidine). OBJECTIVE: To evaluate in the clinical setting the frequency and risk factors associated with the QT-interval prolongation induced by meperidine. RESEARCH DESIGN AND METHODS: We recruited patients requiring meperidine administration and recorded their medical history and comorbidities predisposing to QT-interval prolongation. Ionograms and electrocardiograms (ECGs) were performed at baseline and during treatment; QT was corrected using the Bazzet, Fridericia, Framinghan, and Hogdes formulas...
August 11, 2016: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27342387/effects-of-therapeutic-and-supratherapeutic-doses-of-oral-tedizolid-phosphate-on-cardiac-repolarisation-in-healthy-volunteers-a-randomised-controlled-study
#3
Shawn Flanagan, Jeffrey Litwin, Edward Fang, Philippe Prokocimer
Drug-induced prolongation of the QT interval on the electrocardiogram (ECG) infrequently results in Torsades de pointes, a potentially fatal arrhythmia. Therefore, thorough QT analysis of new drugs is a regulatory requirement. The objective of this phase 1 study was to assess the effects of oral tedizolid phosphate on the QT interval corrected with Fridericia's formula (QTcF) in healthy adult subjects. A single therapeutic dose (200 mg) and a supratherapeutic dose (1200 mg) of tedizolid phosphate were administered to characterise QTc changes following typical systemic exposure and with markedly higher exposures, respectively...
July 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/27195944/how-to-determine-cardiac-ion-channels-targeted-by-drugs-using-the-isolated-rabbit-ventricular-wedge-model
#4
Guizhi Liu, Tong Liu, Daniel Cohen, Tengxian Liu, Gan-Xin Yan
INTRODUCTION: The rabbit left ventricular wedge (RLVW) has been demonstrated as a highly sensitive and specific preclinical model in assessing drug-induced QT prolongation and proarrhythmias. However, there is a need to determine drugs' cardiac ion channel profiles beyond QT measurement. In this study, we present an approach to determine cardiac ion channels targeted by drugs with analyzing a few key ECG parameters plus a contractility parameter obtained from the RLVW. METHODS: The RLVW assay was used for testing 18 drugs with well-known ion channel profiles...
September 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27189953/fluconazole-induced-long-qt-syndrome-via-impaired-human-ether-a-go-go-related-gene-herg-protein-trafficking-in-rabbits
#5
Jinli Wang, Guan Wang, Xiaoqing Quan, Lei Ruan, Yang Liu, Yanfei Ruan, Nian Liu, Cuntai Zhang, Rong Bai
AIMS: hERG protein trafficking deficiency has long been known in drug-induced long QT syndrome (LQTS). However, validated evidence from in vivo data kept scanty. Our goal was to investigate the proarrhythmic action of fluconazole and its underlying mechanism in an animal model. METHODS AND RESULTS: Twenty female Japanese long-eared white rabbits were randomly distributed into a control group and a fluconazole group for a chronic 2-week treatment. The control group was treated with 0...
May 17, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/27131070/drug-induced-brugada-syndrome-clinical-characteristics-and-risk-factors
#6
Maayan Konigstein, Raphael Rosso, Guy Topaz, Pieter G Postema, Limor Friedensohn, Karin Heller, David Zeltser, Bernard Belhassen, Arnon Adler, Sami Viskin
BACKGROUND: Cardiac arrest may result from seemingly innocuous medications that do not necessarily have cardiac indications. The best-known example is the drug-induced long QT syndrome. A less known but not necessarily less important form of drug-induced proarrhythmia is the drug-induced Brugada syndrome. OBJECTIVE: The purpose of this study was to identify clinical and ECG risk markers for drug-induced Brugada syndrome. METHODS: Reports of drug-induced Brugada syndrome recounted by an international database (http://www...
May 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27095299/qt-interval-correction-for-drug-induced-changes-in-body-temperature-during-integrated-cardiovascular-safety-assessment-in-regulatory-toxicology-studies-in-dogs-a-case-study
#7
Abdel-Ilah El Amrani, Francine El Amrani-Callens, Stéphane Loriot, Pramila Singh, Roy Forster
INTRODUCTION: Cardiovascular safety assessment requires accurate evaluation of QT interval, which depends on the length of the cardiac cycle and also on core body temperature (BT). Increases in QT interval duration have been shown to be associated with decreases in BT in dogs. METHODS: An example of altered QT interval duration associated with changes in body temperature observed during a 4-week regulatory toxicology study in dogs is presented. Four groups of Beagle dogs received the vehicle or test item once on Day 1, followed by a 4-week observation period...
September 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27022719/the-comparison-of-biodistribution-efficacy-and-toxicity-of-two-pegylated-liposomal-doxorubicin-formulations-in-mice-bearing-c-26-colon-carcinoma-a-preclinical-study
#8
K Razavi-Azarkhiavi, A H Jafarian, K Abnous, B M Razavi, K Shirani, M Zeinali, M R Jaafari, G Karimi
BACKGROUND: Over the past several years, the considerable attention has been progressively given to liposomal formulations of anthracyclines. SinaDoxosome(®) (Exir Nano Sina Company, Iran) is a pegylated liposomal doxorubicin (DOX) which approved by Food and Drug Administration of IRAN for treatment of some types of cancer. The aim of this study was to compare the biodistribution, efficacy, cardiotoxicity and hepatotoxicity of SinaDoxosome(®) with Caelyx(®) in mice bearing C-26 colon carcinoma...
June 2016: Drug Research
https://www.readbyqxmd.com/read/26992360/eeg-in-non-clinical-drug-safety-assessments-current-and-emerging-considerations
#9
Simon Authier, Marcus S Delatte, Mary-Jeanne Kallman, Joanne Stevens, Carrie Markgraf
Electroencephalogram (EEG) data in nonclinical species can play a critical role in the successful evaluation of a compound during drug development, particularly in the evaluation of seizure potential and for monitoring changes in sleep. Yet, while non-invasive electrocardiogram (ECG) monitoring is commonly included in preclinical safety studies, pre-dose or post-dose EEG assessments are not. Industry practices as they relate to preclinical seizure liability and sleep assessments are not well characterized and the extent of preclinical EEG testing varies between organizations...
September 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/26969315/fixed-time-induction-of-ovulation-in-camels-superovulated-by-different-ecg-modalities-during-the-transition-period-in-egypt-superovulation-in-camels-during-the-transition-period
#10
Marwa Ahmed Khalifa, Sherif Abdel-Razzak Rateb, Khalid Ahmed El-Bahrawy
The current investigation aimed to establish a fixed-time induction of ovulation/ insemination protocol in camels superovulated by different equine chorionic gonadotropin (eCG) regimens during the transition period in Egypt (mid-October to mid-November). Seventeen pluriparous camels, Camelus dromedarius, were used. All females retained controlled intra-vaginal drug releasers (CIDRs) for 13 consecutive days, and at CIDR withdrawal, the camels were randomly divided into three groups. The control group (n = 5) received 1 ml saline intra-muscularly (i...
April 2016: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/26966107/a-comparison-of-subhypnotic-doses-of-propofol-and-midazolam-during-spinal-anaesthesia-for-elective-caesarean-section
#11
Monika Danielak-Nowak, Ewa Musioł, Danuta Arct-Danielak, Izabela Duda, Karol Ludwik
BACKGROUND: This study compared two types of sedation in pregnant women receiving subarachnoid anaesthesia for elective Caesarean section. METHODS: This prospective randomised study included 56 women. Patients were sedated with propofol (PROP group, n = 27) or midazolam (MID group, n = 29) via intravenous infusion after extraction of the foetus. The following parameters were assessed at five-minute intervals: degree of sedation, heart rate, arterial pressure, ECG recording and arterial haemoglobin oxygen saturation...
2016: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/26960809/drug-drug-interactions-and-qt-prolongation-as-a-commonly-assessed-cardiac-effect-comprehensive-overview-of-clinical-trials
#12
Barbara Wiśniowska, Zofia Tylutki, Gabriela Wyszogrodzka, Sebastian Polak
BACKGROUND: Proarrhythmia assessment is one of the major concerns for regulatory bodies and pharmaceutical industry. ICH guidelines recommending preclinical tests have been established in attempt to eliminate the risk of drug-induced arrhythmias. However, in the clinic, arrhythmia occurrence is determined not only by the inherent property of a drug to block ion currents and disturb electrophysiological activity of cardiac myocytes, but also by many other factors modifying individual risk of QT prolongation and subsequent proarrhythmia propensity...
2016: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/26958096/effect-of-calcitonin-gene-related-peptide-antagonist-on-the-cardiovascular-events-mortality-and-prostaglandin-e2-production-by-nitrate-induced-tolerant-rats-with-acute-myocardial-infarction
#13
Tamar Kezeli, Tamari Rukhadze, Nikoloz Gongadze, Galina Sukoyan, Nino Dolidze, Mariam Chipashvili, Makrine Mirziashvili
BACKGROUND: Anti-ischemic effects of NO releasing by nitroglycerin (NTG) and the release of calcitonin gene-related peptide (CGRP) are involved in the decrease of vascular remodeling in different cardiovascular diseases. Using a nitrate-free period is still generally required to prevent nitrate tolerance and should be used as the first-line option to maintain adequate symptom control and on an individual basis. Personalized anti-ischemic concerns require the urgent change of paradigm from interventional measures to predictive, preventive, and personalized treatment with organic nitrates and its combination with drugs that may improve prognosis and drugs that can be added for patients who remain symptomatic despite therapy with the other classes of agents...
2016: EPMA Journal
https://www.readbyqxmd.com/read/26950553/a-thorough-qt-study-to-evaluate-the-qtc-prolongation-potential-of-two-neuropsychiatric-drugs-quetiapine-and-escitalopram-in-healthy-volunteers
#14
Anhye Kim, Kyoung Soo Lim, Howard Lee, Hyewon Chung, Seo Hyun Yoon, Kyung-Sang Yu, Joo-Youn Cho, In-Jin Jang, Jae-Yong Chung
Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers...
July 2016: International Clinical Psychopharmacology
https://www.readbyqxmd.com/read/26921760/magnitude-of-increase-in-qtc-interval-after-initiation-of-dofetilide-in-patients-with-persistent-atrial-fibrillation-is-associated-with-increased-rates-of-pharmacological-cardioversion-and-long-term-freedom-from-recurrent-atrial-fibrillation
#15
Henry D Huang, Jonathan W Waks, Daniel A Steinhaus, Peter Zimetbaum
BACKGROUND: Dofetilide is a class III antiarrhythmic drug approved for the treatment of atrial fibrillation (AF). Dofetilide-induced corrected QT (QTc) interval prolongation is a surrogate for the degree of drug effect, but the relationships between drug-induced QTc interval prolongation, pharmacological cardioversion (PCV), and freedom from recurrent AF are unclear. OBJECTIVE: The purpose of this study was to assess associations between QTc interval change during dofetilide initiation and PCV and long-term AF recurrence...
July 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/26784016/detecting-moxifloxacin-induced-qtc-prolongation-in-thorough-qt-and-early-clinical-phase-studies-using-a-highly-automated-ecg-analysis-approach
#16
Gopi Krishna Panicker, Dilip R Karnad, Pramod Kadam, Fabio Badilini, Anil Damle, Snehal Kothari
BACKGROUND AND PURPOSE: Exposure-response (ER) modelling (concentration-QTc analysis) is gaining as much acceptance as the traditional by-time analysis of the placebo-adjusted change from baseline in the QTc interval (ΔΔQTcF). It has been postulated that intensive ECG analysis and ER modelling during early-phase drug development could be a cost-effective approach of estimating QT liability of a new drug, in a small number of subjects. EXPERIMENTAL APPROACH: We used a highly automated analysis of ECGs from 46 subjects from a crossover thorough QT/QTc study to detect ΔΔQTcF with moxifloxacin...
April 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/26648606/risk-assessment-of-drug-induced-qt-prolongation
#17
REVIEW
Geoffrey K Isbister
Drugs can cause prolongation of the QT interval, alone or in combination, potentially leading to fatal arrhythmias such as torsades de pointes. When prescribing drugs that prolong the QT interval, the balance of benefit versus harm should always be considered. Readouts from automated ECG machines are unreliable. The QT interval should be measured manually. Changes in heart rate influence the absolute QT interval. Heart rate correction formulae are inaccurate, particularly for fast and slow heart rates. The QT nomogram, a plot of QT interval versus heart rate, can be used as a risk assessment tool to detect an abnormal QT interval...
February 2015: Australian Prescriber
https://www.readbyqxmd.com/read/26377788/contractile-function-assessment-by-intraventricular-balloon-alters-the-ability-of-regional-ischaemia-to-evoke-ventricular-fibrillation
#18
Catherine D E Wilder, Radwa Masoud, Duygu Yazar, Brett A O'Brien, Thomas R Eykyn, Michael J Curtis
BACKGROUND AND PURPOSE: In drug research using the rat Langendorff heart preparation, it is possible to study left ventricular (LV) contractility using an intraventricular balloon (IVB), and arrhythmogenesis during coronary ligation-induced regional ischaemia. Assessing both concurrently would halve animal requirements. We aimed to test the validity of this approach. EXPERIMENTAL APPROACH: The electrocardiogram (ECG) and LV function (IVB) were recorded during regional ischaemia of different extents in a randomized and blinded study...
January 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/26324176/sex-differences-in-drug-induced-changes-in-ventricular-repolarization
#19
RANDOMIZED CONTROLLED TRIAL
Jose Vicente, Lars Johannesen, Jay W Mason, Esther Pueyo, Norman Stockbridge, David G Strauss
INTRODUCTION: Heart rate corrected QT (QTc) interval prolongation is a predictor of drug-induced torsade de pointes, a potentially fatal ventricular arrhythmia that disproportionately affects women. This study assesses whether there are sex differences in the ECG changes induced by four different hERG potassium channel blocking drugs. METHODS AND RESULTS: Twenty-two healthy subjects (11 women) received a single oral dose of dofetilide, quinidine, ranolazine, verapamil and placebo in a double-blind 5-period crossover study...
November 2015: Journal of Electrocardiology
https://www.readbyqxmd.com/read/26304046/the-utility-of-a-non-significant-coronary-angiogram
#20
T K M Wang, T H T Oh, C B Samaranayake, M W I Webster, J T Stewart, T Watson, C Ellis, P N Ruygrok
BACKGROUND: Coronary angiography is the gold standard for assessing coronary artery disease (CAD). In many patients with chest pain, no or mild CAD (< 50% stenosis) is found. It is uncertain whether this 'non-significant' result influences management and outcomes. We reviewed characteristics and outcomes in a contemporary cohort of chest pain referrals who had mild or absent CAD on coronary angiography. METHOD: All patients undergoing coronary angiography at Auckland City Hospital during July 2010-October 2011 were reviewed (n = 2983)...
December 2015: International Journal of Clinical Practice
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