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Drug-induced QTc interval prolongation

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https://www.readbyqxmd.com/read/28429460/automated-t-wave-analysis-can-differentiate-acquired-qt-prolongation-from-congenital-long-qt-syndrome
#1
Alan Sugrue, Peter A Noseworthy, Vaclav Kremen, J Martijn Bos, Bo Qiang, Ram K Rohatgi, Yehu Sapir, Zachi I Attia, Peter Brady, Pedro J Caraballo, Samuel J Asirvatham, Paul A Friedman, Michael J Ackerman
BACKGROUND: Prolongation of the QT on the surface electrocardiogram can be due to either genetic or acquired causes. Distinguishing congenital long QT syndrome (LQTS) from acquired QT prolongation has important prognostic and management implications. We aimed to investigate if quantitative T-wave analysis could provide a tool for the physician to differentiate between congenital and acquired QT prolongation. METHODS: Patients were identified through an institution-wide computer-based QT screening system which alerts the physician if the QTc ≥ 500 ms...
April 21, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/28299825/fingolimod-gilenya-%C3%A2-in-multiple-sclerosis-bradycardia-atrioventricular-blocks-and-mild-effect-on-the-qtc-interval-something-to-do-with-the-l-type-calcium-channel
#2
Sylvie Pilote, Chantale Simard, Benoit Drolet
Cardiac arrhythmias and ECG abnormalities including bradycardia, prolongation of the QT interval, and atrioventricular (AV) conduction blocks have been extensively observed with fingolimod, the first marketed oral drug for treating the relapsing-remitting form of multiple sclerosis. This study was aiming to further elucidate the effects of fingolimod on cardiac electrophysiology at three different levels: (i) in vitro, (ii) ex vivo, and (iii) in vivo. (i) Patch-clamp experiments in whole cell configuration were performed on Cav 1...
March 16, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28245963/characterization-of-microminipigs-as-an-in%C3%A2-vivo-experimental-model-for-cardiac-safety-pharmacology
#3
Suchitra Matsukura, Yuji Nakamura, Xin Cao, Takeshi Wada, Hiroko Izumi-Nakaseko, Kentaro Ando, Hiroshi Yamazaki, Atsushi Sugiyama
We pharmacologically characterized microminipigs as an in vivo experimental model by assessing cardiovascular effects of pilsicainide, verapamil and E-4031, which can preferentially inhibit cardiac Na(+), Ca(2+) and K(+) channels, respectively. Intravenous infusion of 1 mg/kg of pilsicainide (n = 4), 0.1 mg/kg of verapamil (n = 4) and 0.01 followed by 0.1 mg/kg of E-4031 (n = 5) over 10 min decreased the heart rate, mean blood pressure and ventricular contractility. Moreover, pilsicainide prolonged the PR interval, QRS width and QTc; verapamil prolonged the PR interval, but shortened the QRS width and QTc; and E-4031 prolonged the QTc, whereas no substantial change was detected in the PR interval or QRS width...
February 11, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28213480/common-genetic-variant-risk-score-is-associated-with-drug-induced-qt-prolongation-and-torsade-de-pointes-risk-a-pilot-study
#4
David G Strauss, Jose Vicente, Lars Johannesen, Ksenia Blinova, Jay W Mason, Peter Weeke, Elijah R Behr, Dan M Roden, Ray Woosley, Gulum Kosova, Michael A Rosenberg, Christopher Newton-Cheh
BACKGROUND: Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known. METHODS: We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28126150/drug-induced-qtc-prolongation
#5
Fady S Riad, Andrew M Davis, Michael P Moranville, John F Beshai
QTc prolongation has a high prevalence of and is associated with increased all-cause mortality. Nonetheless, QTc prolonging medications are often used during patient hospitalizations despite baseline prolongation and QTc changes. Data regarding the real-world relative risk of QTc prolongation in the hospital setting are lacking. In this study, we sought to quantify the degree and relative risk of QTc prolongation in patients receiving Arizona Center for Education and Research on Therapeutics (AzCERT) "known risk" medications...
January 15, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28100427/the-possible-role-of-propofol-in-drug-induced-torsades-de-pointes-a-real-world-single-center-analysis
#6
Victor A Abrich, Harish Ramakrishna, Arjun Mehta, Farouk Mookadam, Komandoor Srivathsan
BACKGROUND: Torsades de pointes (TdP) is a polymorphic ventricular tachycardia associated with QT prolongation. Propofol is a sedative-anesthetic with proarrhythmic effects on cardiac myocytes. We performed a retrospective study to determine the incidence of TdP following propofol exposure at Mayo Clinic (Rochester, MN) from 08/11/1998-11/20/2015. METHODS: We queried our database using key search terms to identify patients exposed to propofol who developed TdP perioperatively or during non-surgical sedation...
April 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28097003/application-of-a-systems-pharmacology-model-for-translational-prediction-of-herg-mediated-qtc-prolongation
#7
Verena Gotta, Zhiyi Yu, Frank Cools, Karel van Ammel, David J Gallacher, Sandra A G Visser, Frederick Sannajust, Pierre Morissette, Meindert Danhof, Piet H van der Graaf
Drug-induced QTc interval prolongation (Δ QTc) is a main surrogate for proarrhythmic risk assessment. A higher in vivo than in vitro potency for hERG-mediated QTc prolongation has been suggested. Also, in vivo between-species and patient populations' sensitivity to drug-induced QTc prolongation seems to differ. Here, a systems pharmacology model integrating preclinical in vitro (hERG binding) and in vivo (conscious dog Δ QTc) data of three hERG blockers (dofetilide, sotalol, moxifloxacin) was applied (1) to compare the operational efficacy of the three drugs in vivo and (2) to quantify dog-human differences in sensitivity to drug-induced QTc prolongation (for dofetilide only)...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28065822/detecting-drug-induced-changes-in-ecg-parameters-using-jacketed-telemetry-effect-of-different-data-reduction-techniques
#8
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...
January 5, 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
#9
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/27990843/impact-of-qt-interval-prolongation-following-antiarrhythmic-drug-therapy-on-left-ventricular-function
#10
Konstantinos Chouchoulis, John Chiladakis, Nikolaos Koutsogiannis, Periklis Davlouros, Maria Kaza, Dimitrios Alexopoulos
AIM: We assessed whether antiarrhythmic drug-induced QT interval prolongation affects left ventricular function. METHODS: Study population included 54 patients with symptomatic recent onset atrial fibrillation spontaneously cardioverted to sinus rhythm. Electrocardiographic and echocardiographic studies were done before initiating and after achieving drug's steady state. RESULTS: Significantly prolonged corrected QT interval (QTc) was noticed following only sotalol and amiodarone...
January 2017: Future Cardiology
https://www.readbyqxmd.com/read/27920831/assessment-of-drug-induced-proarrhythmias-due-to-pilsicainide-in-patients-with-atrial-tachyarrhythmias
#11
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/27899938/detailed-analysis-of-the-impact-of-age-on-the-qt-interval
#12
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/27809883/alternatives-to-currently-used-antimalarial-drugs-in-search-of-a-magic-bullet
#13
REVIEW
Akshaya Srikanth Bhagavathula, Asim Ahmed Elnour, Abdulla Shehab
Malaria is a major cause of morbidity and mortality in many African countries and parts of Asia and South America. Novel approaches to combating the disease have emerged in recent years and several drug candidates are now being tested clinically. However, it is long before these novel drugs can hit the market, especially due to a scarcity of safety and efficacy data.To reduce the malaria burden, the Medicines for Malaria Venture (MMV) was established in 1999 to develop novel medicines through industry and academic partners' collaboration...
November 4, 2016: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/27788262/resveratrol-reverses-functional-chagas-heart-disease-in-mice
#14
Glaucia Vilar-Pereira, Vitor C Carneiro, Hilton Mata-Santos, Amanda R R Vicentino, Isalira P Ramos, Naira L L Giarola, Daniel F Feijó, José R Meyer-Fernandes, Heitor A Paula-Neto, Emiliano Medei, Marcelo T Bozza, Joseli Lannes-Vieira, Claudia N Paiva
Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27747715/coma-after-quetiapine-fumarate-intentional-overdose-in-a-71-year-old-man-a-case-report
#15
S Gibiino, A Trappoli, B Balzarro, A R Atti, D De Ronchi
A 71-year-old man developed coma with severe respiratory failure, hypotension, and tachycardia induced by the intentional ingestion of quetiapine fumarate extended release (XR) 20 g. At the time, he had been treated for bipolar depression with venlafaxine 75 mg/day, lamotrigine 100 mg/day, pregabalin 75 mg/day, and quetiapine XR 400 mg/day for approximately 1 year. Comorbidities were hypertension treated with metoprolol, diabetes mellitus type 2 treated with metformin, and benign prostatic hyperplasia treated with silodosin...
December 2015: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/27703966/marked-qtc-prolongation-and-torsades-de-pointes-in-patients-with-chronic-inflammatory-arthritis
#16
Pietro Enea Lazzerini, Pier Leopoldo Capecchi, Iacopo Bertolozzi, Gabriella Morozzi, Sauro Lorenzini, Antonella Simpatico, Enrico Selvi, Maria Romana Bacarelli, Maurizio Acampa, Deana Lazaro, Nabil El-Sherif, Mohamed Boutjdir, Franco Laghi-Pasini
Mounting evidence indicates that in chronic inflammatory arthritis (CIA), QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in rheumatoid arthritis (RA) patients, the risk of sudden cardiac death is significantly increased when compared to non-RA subjects...
2016: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/27647678/commentary-on-levofloxacin-induced-qtc-prolongation-depends-on-the-time-of-drug-administration
#17
C Garnett, L Johannesen
Circadian variations in the corrected QT (QTc) interval have been documented in clinical trials. Animal models show circadian variations in expression of the cardiac ion channels that are necessary to maintain the heart's electrophysiological properties. Can these diurnal rhythms in QTc affect the ability of a drug to delay cardiac repolarization?
September 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27621502/ranolazine-induced-reversible-t-wave-inversions-with-prolonged-qtc-interval-progressive-multifocal-leukoencephalopathy-linked-to-fingolimod-losartan-induced-sprue-like-enteropathy-nivolumab-induced-psoriasiform-skin-eruption-hepatitis-b-reactivation-with-hepatitis
#18
EDITORIAL
Michael A Mancano
The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MED WATCH program (800-FDA-1088). If you have reported an interesting, preventable ADR to MED WATCH, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested...
November 2015: Hospital Pharmacy
https://www.readbyqxmd.com/read/27547470/loperamide-induced-life-threatening-ventricular-arrhythmia
#19
Ankit Upadhyay, Vijaykumar Bodar, Mohammad Malekzadegan, Sharanjit Singh, William Frumkin, Aditya Mangla, Kaushik Doshi
Loperamide is over-the-counter antidiarrheal agent acting on peripherally located μ opioid receptors. It is gaining popularity among drug abusers as opioid substitute. We report a case of a 46-year-old male that was presented after cardiac arrest. After ruling out ischemia, cardiomyopathy, pulmonary embolism, central nervous system pathology, sepsis, and other drug toxicity, we found out that patient was using around 100 mg of Loperamide to control his chronic diarrhea presumably because of irritable bowel syndrome for last five years and consumed up to 200 mg of Loperamide daily for last two days before the cardiac arrest...
2016: Case Reports in Cardiology
https://www.readbyqxmd.com/read/27509828/meperidine-induced-qtc-interval-prolongation-prevalence-risk-factors-and-correlation-to-plasma-drug-and-metabolite-concentrations%C3%A2
#20
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
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