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drug induced ECG changes

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https://www.readbyqxmd.com/read/28866768/providers-response-to-clinical-decision-support-for-qt-prolonging-drugs
#1
Sunita Sharma, J Martijn Bos, Robert F Tarrell, Gyorgy J Simon, Bruce W Morlan, Michael J Ackerman, Pedro J Caraballo
Commonly used drugs in hospital setting can cause QT prolongation and trigger life-threatening arrhythmias. We evaluate changes in prescribing behavior after the implementation of a clinical decision support system to prevent the use of QT prolonging medications in the hospital setting. We conducted a quasi-experimental study, before and after the implementation of a clinical decision support system integrated in the electronic medical record (QT-alert system). This system detects patients at risk of significant QT prolongation (QTc>500ms) and alerts providers ordering QT prolonging drugs...
September 2, 2017: Journal of Medical Systems
https://www.readbyqxmd.com/read/28800628/genome-wide-analysis-of-sotalol-induced-ikr-inhibition-during-ventricular-repolarization-generepol-study-lack-of-common-variants-with-large-effect-sizes
#2
Joe-Elie Salem, Marine Germain, Jean-Sébastien Hulot, Pascal Voiriot, Bruno Lebourgeois, Jean Waldura, David-Alexandre Tregouet, Beny Charbit, Christian Funck-Brentano
Many drugs used for non-cardiovascular and cardiovascular purposes, such as sotalol, have the side effect of prolonging cardiac repolarization, which can trigger life-threatening cardiac arrhythmias by inhibiting the potassium-channel IKr (KCNH2). On the electrocardiogram (ECG), IKr inhibition induces an increase in QTc and Tpeak-Tend (TpTe) interval and a decrease of T wave maximal amplitude (TAmp). These changes vary markedly between subjects, suggesting the existence of predisposing genetic factors. 990 healthy individuals, prospectively challenged with an oral 80mg sotalol dose, were monitored for changes in ventricular repolarization on ECG between baseline and 3 hours post dosing...
2017: PloS One
https://www.readbyqxmd.com/read/28712169/analytic-study-in-patients-presenting-to-a-tertiary-care-hospital-regarding-the-artemether-lumefantrine-induced-qtc-interval-changes-in-ecg
#3
Aliena Badshah, Iqbal Haider, Shams Suleman
BACKGROUND: Malaria is one of the most common causes of morbidity and mortality in our part of the world. Artemether-Lumefantrine (AL) Combination therapy is widely used for the treatment of malaria both in outpatients and inpatients hospital settings. Some of the previous anti-malarial were associated with prolongation of QTc interval. Similar query was raised about AL therapy. This study was conducted to determine the risk of QTc interval prolongation in ECG of patients with Falciparum malaria using oral Artemether-Lumefantrine (AL) combination therapy...
January 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28552773/voltage-gated-ion-channels-blockade-is-the-underlying-mechanism-of-bimu8-induced-cardiotoxicity
#4
Shahid Muhammad Iqbal, Rosa Lemmens-Gruber
BIMU8 is a 5-HT4a receptor agonist and used as an experimental drug to counteract opioid induced respiratory depression. In preliminary experiments serious disturbances in ECG were observed in anesthetized rabbits which prompted us to explore the underlying cause of BIMU8 induced abnormal changes in ECG recordings. Electrophysiological experiments were performed on HEK-293 cells expressing hERG, CaV1.2 and NaV1.5 ion channels. In whole-cell recordings BIMU8 effectively blocked these three channels, with IC50 values of 0...
August 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28544933/cardiotoxic-effect-of-levofloxacin-and-ciprofloxacin-in-rats-with-without-acute-myocardial-infarction-impact-on-cardiac-rhythm-and-cardiac-expression-of-kv4-3-kv1-2-and-nav1-5-channels
#5
Ahmed M Abdelrady, Sawsan A Zaitone, Noha E Farag, Manal S Fawzy, Yasser M Moustafa
Prolongation of QT interval is possible with fluoroquinolones, yet the underlying contributing factors have not been elucidated. Two widely used fluoroquinolone drugs were at the focus of this study in rats with/without acute myocardial dysfunction (AMI) induced by isoproterenol. The effects of levofloxacin and ciprofloxacin on the cardiac mRNA expression of rat Kv4.3, Kv1.2 and Nav1.5 mRNAs were determined. Administration of the two antibiotics produced dose-dependent changes in ECG parameters that were more prominent in rats with AMI than healthy rats; this was accompanied by elevations in serum lactate dehydrogenase and creatine kinase-MB...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28528724/twelve-lead-ambulatory-electrocardiographic-monitoring-in-brugada-syndrome-potential-diagnostic-and-prognostic-implications
#6
Belinda Gray, Adrienne Kirby, Peter Kabunga, Saul B Freedman, Laura Yeates, Ajita Kanthan, Caroline Medi, Anthony Keech, Christopher Semsarian, Raymond W Sy
BACKGROUND: Patients with Brugada syndrome (BrS) are diagnosed and risk stratified on the basis of a spontaneous or drug-induced type 1 electrocardiographic (ECG) pattern, often at single time points not accounting for variation throughout the day. OBJECTIVES: The purpose of this study was to prospectively assess the overall burden of type 1 Brugada ECG changes using 12-lead 24-hour Holter monitoring and evaluate association with cardiac events. METHODS: From July 1, 2013 to December 31, 2015, patients with BrS were recruited from 3 Australian centers and the Australian Genetic Heart Disease Registry...
June 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28456577/evaluation-of-processed-borax-as-antidote-for-aconite-poisoning
#7
Prasanta Kumar Sarkar, Pradeep K Prajapati, Vinay J Shukla, Basavaiah Ravishankar
ETHNOPHARMACOLOGICAL RELEVANCE: Aconite root is very poisonous; causes cardiac arrhythmias, ventricular fibrillation and ventricular tachycardia. There is no specific antidote for aconite poisoning. In Ayurveda, dehydrated borax is mentioned for management of aconite poisoning. AIM OF THE STUDY: The investigation evaluated antidotal effect of processed borax against acute and sub-acute toxicity, cardiac toxicity and neuro-muscular toxicity caused by raw aconite...
April 26, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28342858/aqueous-extract-from-leaf-of-artocarpus-altilis-provides-cardio-protection-from-isoproterenol-induced-myocardial-damage-in-rats-negative-chronotropic-and-inotropic-effects
#8
Chukwuemeka Nwokocha, Javier Palacios, Mario J Simirgiotis, Jemesha Thomas, Magdalene Nwokocha, Lauriann Young, Rory Thompson, Fredi Cifuentes, Adrian Paredes, Rupika Delgoda
ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Artocarpus altilis (Parkinson ex F.A.Zorn, Fosberg) (Moraceae) are used in the management of hypertension; this study assessed the cardio-protective effects of the leaf extract on isoproterenol (ISO) induced myocardial damage in rats. MATERIAL AND METHODS: Twenty (20) adult male Sprague-Dawley rats (175-230g) were divided into 5 groups. Group 1 (Control), 2 (AA) received 50mg/Kg Artocarpus altilis (AA) only; 3 (ISO) received 85mg/Kg ISO only; 4 (ISO+AA/50) and 5 (ISO+AA/100) received 50 and 100mg/Kg AA respectively for 6 days, after induced with ISO twice (85mg/Kg) at a 24-h period...
May 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28326201/hyperkalemia-induced-brugada-phenocopy-a-rare-ecg-manifestation
#9
Muhammad Ameen, Ghulam Akbar, Naeem Abbas, Ghazi Mirrani
Brugada syndrome (BrS) is an inherited disorder of cardiac ion channels characterized by peculiar ECG findings predisposing individuals to ventricular arrhythmias, syncope, and sudden cardiac death (SCD). Various electrolyte disturbances and ion channels blocking drugs could also provoke BrS ECG findings without genetic BrS. Clinical differentiation and recognition are essential for guiding the legitimate action. Hyperkalemia is well known to cause a wide variety of ECG manifestations. Severe hyperkalemia can even cause life threatening ventricular arrhythmias and cardiac conduction abnormalities...
2017: Case Reports in Cardiology
https://www.readbyqxmd.com/read/28236352/antazoline-insights-into-drug-induced-electrocardiographic-and-hemodynamic-effects-results-of-the-elephant-ii-substudy
#10
Roman Piotrowski, Joanna Giebułtowicz, Jakub Baran, Agnieszka Sikorska, Dagmara Gralak-Łachowska, Małgorzata Soszyńska, Piotr Wroczyński, Piotr Kułakowski
BACKGROUND: Antazoline is an old antihistaminic and new antiarrhythmic agent with unknown mechanisms of action which recently has been shown to effectively terminate atrial fibrillation. The aim of study was to examine the effects of antazoline on hemodynamic and ECG parameters. METHODS: Antazoline was given intravenously in three 100 mg boluses to 10 healthy volunteers (four males, mean age 40 + 11 years). Hemodynamic and ECG parameters were measured using impedance cardiography [systolic (sBP), diastolic (dBP), mean (mBP) blood pressure, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and heart rate (HR), P wave, PR interval, QRS complex, QT and corrected QT (QTcF) interval]...
February 25, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/28131707/the-application-of-signal-average-ecg-in-the-prediction-of-recurrences-after-catheter-ablation-of-ventricular-arrhythmias-in-arrhythmogenic-right-ventricular-dysplasia-cardiomyopathy
#11
Ying-Chieh Liao, Fa-Po Chung, Yenn-Jiang Lin, Shih-Lin Chang, Li-Wei Lo, Yu-Feng Hu, Ta-Chuan Tuan, Tze-Fan Chao, Jo-Nan Liao, Chin-Yu Lin, Yao-Ting Chang, Ming-Hsiung Hsieh, Shih-Ann Chen
BACKGROUND: The changes of signal averaged ECG (SAECG) in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) undergoing radiofrequency catheter ablation (RFCA) of ventricular arrhythmias (VAs) remains unknown. METHODS: Between 2010 and 2014, a total of 81 ARVD/C patients underwent endocardial and/or epicardial RFCA for drug-refractory VAs. Seventy patients (mean age 46.2±14.1years, 37 males) achieving acute procedure success (negative inducibility) were enrolled...
June 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28065822/detecting-drug-induced-changes-in-ecg-parameters-using-jacketed-telemetry-effect-of-different-data-reduction-techniques
#12
Matthew Skinner, Guozhen Xing, Jing Lu, Jin Ren, Karen Oldman
INTRODUCTION: Continuous cardiovascular data is routinely collected during preclinical safety assessment of new medicines. This generates large datasets, which must be summarised to analyse and interpret drug effects. We assessed four methods of data reduction of continuous electrocardiogram (ECG) data and examined the impact on the statistical power of the assay. METHODS: Continuous ECG data were collected from a validation study in 6 cynomolgus monkeys using jacketed telemetry...
May 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28065821/an-evaluation-of-the-utility-of-lvdp-dt40-qa-interval-lvdp-dtmin-and-tau-as-indicators-of-drug-induced-changes-in-contractility-and-lusitropy-in-dogs
#13
Michael K Pugsley, Brian Guth, Alan Y Chiang, Jennifer M Doyle, Michael Engwall, Jean-Michel Guillon, Peter K Hoffmann, John E Koerner, Scott W Mittelstadt, Jennifer Beck Pierson, Eric I Rossman, Dustan R Sarazan, Stanley T Parish
INTRODUCTION: The importance of drug-induced effects on the inotropic state of the heart is well known. Unlike hemodynamic and cardiac electrophysiological methods, which have been routinely used in drug safety testing for years, the non-clinical assessment of drug effects on myocardial contractility is used less frequently with no established translation to humans. The goal of these studies was to determine whether assessment of alternate measures of cardiac inotropy could detect drug-induced changes in the contractile state of the heart using drugs known to have clinically relevant positive and negative effects on myocardial contractility...
May 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28003052/population-pharmacokinetic-pharmacodynamic-analysis-to-compare-the-effect-of-moxifloxacin-on-qt-interval-prolongation-between-healthy-korean-and-japanese-subjects
#14
Hyang-Ki Choi, Jin Ah Jung, Tomoe Fujita, Hideki Amano, Jong-Lyul Ghim, Dong-Hwan Lee, Kenichi Tabata, Il-Dae Song, Mika Maeda, Yuji Kumagai, Boaz Mendzelevski, Jae-Gook Shin
PURPOSE: The goal of this study was to evaluate the moxifloxacin-induced QT interval prolongation in healthy male and female Korean and Japanese volunteers to investigate interethnic differences. METHODS: This multicenter, randomized, double-blind, placebo-controlled, 2-way crossover study was conducted in healthy male and female Korean and Japanese volunteers. In each period, a single dose of moxifloxacin or placebo 400 mg was administered orally under fasting conditions...
December 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27943168/hemodialysis-induced-repolarization-abnormalities-on-ecg-are-influenced-by-serum-calcium-levels-and-ultrafiltration-volumes
#15
Hande Ozportakal, Abdullah Ozkok, Ozlem Alkan, Ahmet Sait Bulut, Memduha Boyraz, Mehmet Inanir, Goksel Acar, Ali Riza Odabas
PURPOSE: Hemodialysis (HD) patients are known to have high cardiovascular mortality rate. Sudden cardiac death (SCD) due to arrhythmias causes most of the cardiac deaths. HD per se may lead to ECG abnormalities and ventricular arrhythmias. Monitoring ECG parameters such as corrected QT interval, QT dispersion (QTd), Tpe interval may be useful to stratify the patients with high risk of arrhythmia and SCD. Herein we aimed to investigate the effects of changes in serum electrolyte levels and pH on ECG parameters before and after the HD...
March 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/27560382/a-novel-scn5a-mutation-associated-with-drug-induced-brugada-type-ecg
#16
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
#17
Guillermo Alberto Keller, María Cecilia Villa Etchegoyen, Nicolás Fernández, Nancy Mónica Olivera, Patricia Noemi 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...
March 2017: 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
#18
RANDOMIZED CONTROLLED TRIAL
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
#19
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
#20
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...
July 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
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