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https://www.readbyqxmd.com/read/28202194/study-of-factors-affecting-the-progression-and-termination-of-drug-induced-torsade-de-pointes-in-two-dimensional-cardiac-tissue
#1
Ponnuraj Kirthi Priya, M Ramasubba Reddy
INTRODUCTION: To study the conditions leading to the initiation and termination of drug induced Torsade de pointes (TdP) along with QT prolongation. METHODS: A 2D anisotropic transmural section of the ventricular myocardium is modeled using the TP06 equations and the cells are interconnected with gap junction conductances (GJC). The tissue is remodeled by reducing the repolarization reserve (by increasing calcium current (ICaL)) of all cells thus making them vulnerable to development of early after depolarizations (EADs)...
February 2, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28185059/severe-proarrhythmic-potential-of-the-antiemetic-agents-ondansetron-and-domperidone
#2
Gerrit Frommeyer, Christina Fischer, Christian Ellermann, Philipp S Lange, Dirk G Dechering, Simon Kochhäuser, Michael Fehr, Lars Eckardt
The potential of ondansetron and domperidone, both clinically established antiemetic agents, to increase the QT-interval has been described in several case reports. Therefore, the aim of the present study was to investigate whether these drugs may provoke polymorphic ventricular tachycardia in a sensitive experimental model of drug-induced proarrhythmia. In 10 female rabbits, ondansetron (1, 5 and 10 µM, n = 10) or domperidone (0.5, 1 and 2 µM, n = 8) was infused after obtaining baseline data. Eight endo- and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG reproduced the clinically observed QT-prolongation (ondansetron: 1 µM:+17 ms, 5 µM:+41 ms, 10 µM:+78 ms, p < 0...
February 9, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28182570/long-term-outcome-and-safety-of-prolonged-bedaquiline-treatment-for-multidrug-resistant-tuberculosis
#3
Lorenzo Guglielmetti, Marie Jaspard, Damien Le Dû, Marie Lachâtre, Dhiba Marigot-Outtandy, Christine Bernard, Nicolas Veziris, Jérôme Robert, Yazdan Yazdanpanah, Eric Caumes, Mathilde Fréchet-Jachym
Bedaquiline, a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB), is recommended for a duration of 24 weeks. There are scarce data on patients treated with this drug outside clinical trials.All MDR-TB patients who started treatment from January 1, 2011 to December 31, 2013 and received ≥30 days of bedaquiline were included in a multicentre observational cohort.Among 45 MDR-TB patients, 53% harboured isolates resistant to both fluoroquinolones and second-line injectables, and 38% harboured isolates resistant to one of these drug classes...
December 22, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28178199/combined-use-of-delamanid-and-bedaquiline-to-treat-multidrug-resistant-and-extensively-drug-resistant-tuberculosis-a-systematic-review
#4
REVIEW
Giovanni Battista Migliori, Emanuele Pontali, Giovanni Sotgiu, Rosella Centis, Lia D'Ambrosio, Simon Tiberi, Marina Tadolini, Susanna Esposito
The new drugs delamanid and bedaquiline are increasingly being used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). The World Health Organization, based on lack of evidence, recommends their use under specific conditions and not in combination. No systematic review has yet evaluated the efficacy, safety, and tolerability of delamanid and bedaquiline used in combination. A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of delamanid and bedaquiline-containing regimens in individuals with pulmonary/extrapulmonary disease, which were bacteriologically confirmed as M/XDR-TB...
February 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28174642/prolonged-qt-interval-and-cardiac-arrest-after-a-single-dose-of-amiodarone-in-a-woman-with-turner-s-syndrome
#5
Dorte Guldbrand Nielsen, Jens Cosedis Nielsen, Christian Trolle, Claus Højbjerg Gravholt, Niels Holmark Andersen
Low-dose QT-prolonging drugs may have detrimental effects on women with Turner's syndrome. Preventive measures would be to use potential QT-prolonging drugs with precaution and ensure that both before and during treatment, ECGs are evaluated and drug treatment stopped if the QT interval increases.
February 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28163191/csahi-study-detection-of-drug-induced-ion-channel-receptor-responses-qt-prolongation-and-arrhythmia-using-multi-electrode-arrays-in-combination-with-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#6
Takashi Kitaguchi, Yuta Moriyama, Tomohiko Taniguchi, Sanae Maeda, Hiroyuki Ando, Takaaki Uda, Koji Otabe, Masao Oguchi, Shigekazu Shimizu, Hiroyuki Saito, Atsushi Toratani, Mahoko Asayama, Wataru Yamamoto, Emi Matsumoto, Daisuke Saji, Hiroki Ohnaka, Norimasa Miyamoto
INTRODUCTION: The use of multi-electrode arrays (MEA) in combination with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provides a promising method to predict comprehensive cardiotoxicity, including drug-induced QT prolongation and arrhythmia. We previously demonstrated that MEA in combination with hiPSC-CMs could provide a generalizable platform by using 7 reference drugs at 10 testing facilities. Using this approach, we evaluated responses to reference drugs that modulate a range of cardiac ion currents and have a range of arrhythmogenic effects...
February 2, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28159815/validation-of-the-prognostic-utility-of-the-electrocardiogram-for-acute-drug-overdose
#7
Alex F Manini, Ajith P Nair, Rajesh Vedanthan, David Vlahov, Robert S Hoffman
BACKGROUND: While it is certain that some emergency department patients with acute drug overdose suffer adverse cardiovascular events (ACVE), predicting ACVE is difficult. The prognostic utility of the ECG for heterogeneous drug overdose patients remains to be proven. This study was undertaken to validate previously derived features of the initial ECG associated with ACVE in this population. METHODS AND RESULTS: We performed a prospective validation cohort study to evaluate adult emergency department patients with acute drug overdose at 2 urban university hospitals over 5 years in whom an emergency department admission ECG was performed...
February 3, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28154267/contrast-induced-hyperemia-as-an-alternative-to-drug-induced-hyperemia-in-the-evaluation-of-the-fractional-flow-reserve-in-coronary-lesions
#8
Nobuo Shiode, Tomokazu Okimoto, Hiromichi Tamekiyo, Tomoharu Kawase, Kenichi Yamane, Yuzo Kagawa, Yuto Fujii, Yusuke Ueda, Naoya Hironobe, Yasuko Kato, Yasuhiko Hayashi
Objective Measuring the fractional flow reserve (FFR) requires the induction of coronary hyperemia, usually with adenosine, adenosine triphosphate (ATP), or papaverine. However, adenosine can induce rhythmic complications, and intracoronary boluses of papaverine that prolong the QT interval can cause ventricular tachycardia. Injection of contrast media, which is routinely performed to validate the FFR guidewire placement, also induces hyperemia and may be an alternative method of measuring the FFR. We evaluated the diagnostic accuracy of the FFR after contrast hyperemia (FFRcont) compared to FFR evaluated after intracoronary papaverine (FFRpp)...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28134617/modeling-susceptibility-to-drug-induced-long-qt-with-a-panel-of-subject-specific-induced-pluripotent-stem-cells
#9
Francesca Stillitano, Jens Hansen, Chi-Wing Kong, Ioannis Karakikes, Christian Funck-Brentano, Lin Geng, Stuart Scott, Stephan Reynier, Ma Wu, Yannick Valogne, Carole Desseaux, Joe-Elie Salem, Dorota Jeziorowska, Noël Zahr, Ronald Li, Ravi Iyengar, Roger J Hajjar, Jean-Sébastien Hulot
A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol...
January 30, 2017: ELife
https://www.readbyqxmd.com/read/28128816/-haloperidol-poisoning-in-pediatric-patients
#10
Julio César López-Valdés
: Exposing a child to a potentially toxic substance is an uncommon cause of consultation in childhood. Poisoning by drugs in this age group is commonly due to improper administration by parents or error in dosage by the doctor; also ingestion at own initiative, i.e. self-poisoning. CASE REPORT: A 11 years-old male, drowsy, unresponsive, with bradypsychia, assisted ambulation without increased support arch, resting tremor; obeying orders without verbal response, isochoric pupils, difficulty opening the eyes without facial asymmetry, muscle contracture of platysma, increased muscle tone, tendon reflexes slightly increased, arrhythmic heart sounds without murmurs...
January 2017: Gaceta Médica de México
https://www.readbyqxmd.com/read/28126150/drug-induced-qtc-prolongation
#11
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/28111276/recapitulation-of-clinical-individual-susceptibility-to-drug-induced-qt-prolongation-in-healthy-subjects-using-ipsc-derived-cardiomyocytes
#12
Tadahiro Shinozawa, Koki Nakamura, Masanobu Shoji, Maya Morita, Maya Kimura, Hatsue Furukawa, Hiroki Ueda, Masanari Shiramoto, Kyoko Matsuguma, Yoshikazu Kaji, Ippei Ikushima, Makoto Yono, Shyh-Yuh Liou, Hirofumi Nagai, Atsushi Nakanishi, Keiji Yamamoto, Seigo Izumo
To predict drug-induced serious adverse events (SAE) in clinical trials, a model using a panel of cells derived from human induced pluripotent stem cells (hiPSCs) of individuals with different susceptibilities could facilitate major advancements in translational research in terms of safety and pharmaco-economics. However, it is unclear whether hiPSC-derived cells can recapitulate interindividual differences in drug-induced SAE susceptibility in populations not having genetic disorders such as healthy subjects...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28105256/drug-induced-liver-injury-towards-early-prediction-and-risk-stratification
#13
REVIEW
Emanuel Raschi, Fabrizio De Ponti
Drug-induced liver injury (DILI) is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications and agents listed as causing liver damage (http://livertox.nih.gov/). As it was the case in the past decade with drug-induced QT prolongation/arrhythmia, there is an urgent unmet clinical need to develop tools for risk assessment and stratification in clinical practice and, in parallel, to improve prediction of pre-clinical models to support regulatory steps and facilitate early detection of liver-specific adverse drug events...
January 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28102360/modification-of-distinct-ion-channels-differentially-modulates-ca-2-dynamics-in-primary-cultured-rat-ventricular-cardiomyocytes
#14
Xichun Li, Liping Shen, Fang Zhao, Xiaohan Zou, Yuwei He, Fan Zhang, Chunlei Zhang, Boyang Yu, Zhengyu Cao
Primary cultured cardiomyocytes show spontaneous Ca(2+) oscillations (SCOs) which not only govern contractile events, but undergo derangements that promote arrhythmogenesis through Ca(2+) -dependent mechanism. We systematically examined influence on SCOs of an array of ion channel modifiers by recording intracellular Ca(2+) dynamics in rat ventricular cardiomyocytes using Ca(2+) specific fluorescence dye, Fluo-8/AM. Voltage-gated sodium channels (VGSCs) activation elongates SCO duration and reduces SCO frequency while inhibition of VGSCs decreases SCO frequency without affecting amplitude and duration...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28100427/the-possible-role-of-propofol-in-drug-induced-torsades-de-pointes-a-real-world-single-center-analysis
#15
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...
January 4, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28073687/adverse-event-detection-using-the-fda-post-marketing-drug-safety-surveillance-system-cardiotoxicity-associated-with-loperamide-abuse-and-misuse
#16
Kimberley A Swank, Eileen Wu, Cindy Kortepeter, Jana McAninch, Robert L Levin
OBJECTIVE: The purpose of this investigation was to identify and characterize post-marketing reports of cardiotoxicity, including torsades de pointes (TdP), associated with loperamide use. METHODS: We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database for post-marketing reports of serious cardiac adverse events associated with loperamide use from December 28, 1976 (U.S. drug approval date), through December 14, 2015. We also conducted a Pubmed and Google Scholar search to identify additional published reports of cardiotoxicity associated with loperamide in the medical literature through February 11, 2016...
January 7, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28071178/psychotropic-drugs-and-ventricular-repolarisation-the-effects-on-qt-interval-t-peak-to-t-end-interval-and-qt-dispersion
#17
Tiziano Acciavatti, Giovanni Martinotti, Mariangela Corbo, Eduardo Cinosi, Matteo Lupi, Fabrizio Ricci, Rosa Di Scala, Emilia D'Ugo, Viola De Francesco, Raffaele De Caterina, Massimo di Giannantonio
OBJECTIVE: We aimed to investigate in a clinical setting, the effects of different classes of psychotropic drugs on cardiac electrophysiological measures linked with an increased risk of sudden cardiac death. METHODS: We conducted a cross-sectional study in a population of 1059 psychiatric inpatients studying the effects of various psychotropic drugs on the T-peak to T-end (TpTe) interval, QT dispersion and QT interval. RESULTS: Methadone use showed a strong association with TpTe prolongation (odds ratio (OR)=12...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28070113/pharmacological-characterization-of-microminipig-as-a-model-to-assess-the-drug-induced-cardiovascular-responses-for-non-clinical-toxicity-and-or-safety-pharmacology-studies
#18
Hirofumi Yokoyama, Yuji Nakamura, Hiroyuki Saito, Yukitoshi Nagayama, Kiyotaka Hoshiai, Takeshi Wada, Hiroko Izumi-Nakaseko, Kentaro Ando, Yasuki Akie, Atsushi Sugiyama
We tried to establish the halothane-anesthetized microminipigs as an alternative animal model for non-clinical toxicity and/or safety pharmacology studies. In order to characterize the halothane-anesthetized microminipigs, we firstly clarified the effects of halothane anesthesia on their cardiovascular system (n = 5). Then, we examined the cardiovascular effects of dl-sotalol in doses of 0.1, 0.3 and 1 mg/kg, i.v. on the halothane-anesthetized microminipigs (n = 6). Induction of the halothane anesthesia by itself prolonged the QT interval as well as QTcF, suggesting that the halothane anesthesia can reduce the cardiac repolarization reserve in microminipigs like in dogs...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28066143/acepromazine-inhibits-herg-potassium-ion-channels-expressed-in-human-embryonic-kidney-293-cells
#19
Young Shin Joo, Hong Joon Lee, Jin-Sung Choi, Ki-Wug Sung
The effects of acepromazine on human ether-à-go-go-related gene (hERG) potassium channels were investigated using whole-cell voltage-clamp technique in human embryonic kidney (HEK293) cells transfected with hERG. The hERG currents were recorded with or without acepromazine, and the steady-state and peak tail currents were analyzed for the evaluating the drug effects. Acepromazine inhibited the hERG currents in a concentration-dependent manner with an IC50 value of 1.5 µM and Hill coefficient of 1.1. Acepromazine blocked hERG currents in a voltage-dependent manner between -40 and +10 mV...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28012712/unintended-consequences-of-adjusting-citalopram-prescriptions-following-the-2011-fda-warning
#20
Lauren B Gerlach, Helen C Kales, Donovan T Maust, Claire Chiang, Claire Stano, Hae Mi Choe, Kara Zivin
OBJECTIVES: In 2011, the U.S. Food and Drug Administration (FDA) issued a safety announcement cautioning providers against prescribing citalopram above 40 mg per day given concerns for QT prolongation. We assessed the impact of a health system quality improvement initiative to identify patients taking higher than the recommended dose of citalopram. DESIGN: Retrospective cohort study. SETTING: Nine primary care clinics within the University of Michigan from March 2012 to February 2013...
November 18, 2016: American Journal of Geriatric Psychiatry
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