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https://www.readbyqxmd.com/read/28942951/the-algorithmic-performance-of-j-tpeak-for-drug-safety-clinical-trial
#1
Simon C Chien, Richard E Gregg
INTRODUCTION: The interval from J-point to T-wave peak (JTp) in ECG is a new biomarker able to identify drugs that prolong the QT interval but have different ion channel effects. If JTp is not prolonged, the prolonged QT may be associated with multi ion channel block that may have low torsade de pointes risk. From the automatic ECG measurement perspective, accurate and repeatable measurement of JTp involves different challenges than QT. We evaluated algorithm performance and JTp challenges using the Philips DXL diagnostic 12/16/18-lead algorithm...
August 15, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28940299/a-history-of-drug-induced-torsades-de-pointes-is-associated-with-t-wave-morphological-abnormalities
#2
Tanveer A Bhuiyan, Claus Graff, Jørgen K Kanters, Jacob Melgaard, Egon Toft, Stefan Kääb, Johannes J Struijk
The hypothesis of the study is that TdP history can be better identified using T-wave morphology compared to QTcF at baseline. ECGs were recorded at baseline and during sotalol challenge in 20 patients with a history of TdP (+TdP) and 16 patients without previous TdP (-TdP). The Fridericia-corrected QT interval (QTcF) and T-wave morphology combination score (MCS) were calculated. At baseline, there was no significant difference in QTcF between the groups (+TdP: QTcF = 446±9 ms; -TdP: QTcF = 431±9 ms, p = 0...
September 22, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28904293/characteristics-of-electromechanical-window-in-anesthetized-rabbit-models-of-short-qt-and-long-qt-syndromes
#3
Vudhiporn Limprasutr, Nakkawee Saengklub, Pradtana Meedech, Anusak Kijtawornrat, Robert L Hamlin
The current regulatory guidelines recommend the use of QT interval to assess the risk of arrhythmogenic potential of new chemical entities. Recently, the electromechanical window (EMW), the difference in duration between electrical and mechanical systole, has been proposed as markers for drug-induced torsades de pointes (TdP); however, data of EMW in short QT model are not available. This study aimed to characterize the EMW as a marker for drug-induced ventricular arrhythmias in anesthetized rabbit model of long QT syndrome type 2 (LQT2) and short QT syndrome (SQTS) infused with reference compounds known to lengthen or shorten QT intervals...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28895028/prevalence-of-qt-interval-prolonging-drug-drug-interactions-qt-ddis-in-psychiatry-wards-of-tertiary-care-hospitals-in-pakistan-a-multicenter-cross-sectional-study
#4
Qasim Khan, Mohammad Ismail, Iqbal Haider, Fahadullah Khan
Background QT prolongation and associated arrhythmias, torsades de pointes (TdP), are considerable negative outcomes of many antipsychotic and antidepressant agents frequently used by psychiatric patients. Objective To identify the prevalence, levels, and predictors of QT prolonging drug-drug interactions (QT-DDIs), and AZCERT (Arizona Center for Education and Research on Therapeutics) classification of drugs involved in QT-DDIs. Setting Psychiatry wards of three major tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan...
September 12, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28878692/optimization-of-an-in-silico-cardiac-cell-model-for-proarrhythmia-risk-assessment
#5
Sara Dutta, Kelly C Chang, Kylie A Beattie, Jiansong Sheng, Phu N Tran, Wendy W Wu, Min Wu, David G Strauss, Thomas Colatsky, Zhihua Li
Drug-induced Torsade-de-Pointes (TdP) has been responsible for the withdrawal of many drugs from the market and is therefore of major concern to global regulatory agencies and the pharmaceutical industry. The Comprehensive in vitro Proarrhythmia Assay (CiPA) was proposed to improve prediction of TdP risk, using in silico models and in vitro multi-channel pharmacology data as integral parts of this initiative. Previously, we reported that combining dynamic interactions between drugs and the rapid delayed rectifier potassium current (IKr) with multi-channel pharmacology is important for TdP risk classification, and we modified the original O'Hara Rudy ventricular cell mathematical model to include a Markov model of IKr to represent dynamic drug-IKr interactions (IKr-dynamic ORd model)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28862317/is-prolongation-of-corrected-qt-interval-associated-with-seizures-induced-by-electroconvulsive-therapy-reduced-by-atropine-sulfate
#6
Yoko Suzuki, Miho Miyajima, Katsuya Ohta, Noriko Yoshida, Rie Omoya, Mayo Fujiwara, Takafumi Watanabe, Masaki Okumura, Hiroaki Yamazaki, Masayuki Shintaku, Issei Murata, Shigeru Ozaki, Takeshi Sasaki, Mitsuru Nakamura, Hiroshi Suwa, Tetsuo Sasano, Tokuhiro Kawara, Masato Matsuura, Eisuke Matsushima
BACKGROUND: Electrocardiogram abnormalities have been reported during electroconvulsive therapy (ECT). A corrected QT interval (QTc) prolongation indicates delayed ventricular repolarization, which can trigger ventricular arrhythmias such as torsade de pointes (TdP). We examined the QTc changes during generalized tonic-clonic seizures induced by ECT, and the effects of atropine sulfate on these QTc changes. METHODS: We analyzed heart rate, QT interval, and QTc in 32 patients with depression who underwent ECT (25 women, 67...
September 1, 2017: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/28858645/simulation-study-of-the-ionic-mechanisms-underlying-torsade-de-pointes-in-a-2d-cardiac-tissue
#7
Ponnuraj Kirthi Priya, M Ramasubba Reddy
BACKGROUND: To understand the ionic mechanism behind the genesis of Torsade de Pointes (TdP) occurring with long QT syndrome 2 (LQTS2) in a remodelled transmural tissue. METHODS: The TP06 model is used to simulate the electrical activity of cells in a 2D transmural ventricular model. LQTS2 is realised by reducing the potassium current (IKr) to 0.5 in each cell. Each cell of the tissue is remodelled by increasing the conductance of calcium current (GCaL). The above two factors make the cells prone to early after depolarizations (EADs) development...
August 24, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28855066/emergency-department-approach-to-qtc-prolongation
#8
REVIEW
Ali Pourmand, Maryann Mazer-Amirshahi, Sonya Chistov, Youssef Sabha, Damir Vukomanovic, Mohammed Almulhim
QTc prolongation has been associated with increased risk of developing ventricular tachydysrhythmias, particularly Torsades de Pointes (TdP). QTc prolongation is influenced by many factors including congenital causes, heart rate, metabolic imbalances, and pharmacotherapy. Several commonly used medications in the emergency department (ED), such as antipsychotics and antiemetics, are known to prolong the QT interval. In addition, ED patients may present with conditions that may predispose them to QTc prolongation, such as drug overdose or hypokalemia, which can further complicate management...
August 24, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28853038/drug-induced-qt-prolongation-and-torsades-de-pointes-an-all-exclusive-relationship-or-time-for-an-amicable-separation
#9
Luc M Hondeghem
QT prolongation was perceived as a major antiarrhythmic mechanism, but soon became a surrogate for torsades de pointes (TdP) instead. Drugs that prolong the QT interval range from having potent torsadogenic activity to no proarrhythmic action and even antiarrhythmic effects. Blockade of hERG channels is the primary cause of TdP, but blockade/activation of other channels can also be torsadogenic. TdP is primarily caused by disturbances of TRIaD, but disturbance of wavelength can also contribute to TdP (where TRIaD is triangulation, reverse use dependence, instability and dispersion, and wavelength equals conduction velocity times effective refractory period)...
August 29, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28845232/solifenacin-linked-qt-interval-prolongation-and-torsades-de-pointes
#10
Jonathan J H Bray, Jules C Hancox
No abstract text is available yet for this article.
July 2017: Therapeutic Advances in Drug Safety
https://www.readbyqxmd.com/read/28844424/analysis-of-proarrhythmic-potential-of-an-atypical-antipsychotic-drug-paliperidone-in-the-halothane-anesthetized-dogs
#11
Koki Chiba, Takeshi Wada, Yuji Nakamura, Xin Cao, Mihoko Hagiwara-Nagasawa, Hiroko Izumi-Nakaseko, Kentaro Ando, Koichiro Tanaka, Atsuhiko T Naito, Atsushi Sugiyama
Fatal cases with the use of atypical antipsychotic drug paliperidone have been reported; however, there was no clinical report describing paliperidone-induced torsade de pointes. In this study we assessed its electropharmacological effects together with its proarrhythmic potential in intravenous doses of 0.03, 0.3 and 3 mg/kg using the halothane-anesthetized dogs (n = 5), which could provide approximately 2, 20 and 200 times higher peak plasma drug concentrations than its therapeutic level, respectively...
August 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28836822/a-review-of-ecg-and-qt-interval-measurement-use-in-a-public-psychiatric-inpatient-setting
#12
Ingrid Berling, Rahul Gupta, Cecilia Bjorksten, Felicity Prior, Ian M Whyte, Sherman Berry
OBJECTIVES: There is an increased rate of sudden cardiac death (SCD) in mental health patients. Some antipsychotic medications are known to prolong the QT interval, thus increasing a patient's risk of SCD via the arrhythmia, torsades de pointes (TdP). Our aim was to evaluate assessment for QT prolongation within a public inpatient mental health facility by auditing electrocardiograph (ECG) use. METHODS: We reviewed records of all mental health inpatient admissions to a public emergency mental health inpatient unit between 1 January 2016 and 11 February 2016...
August 1, 2017: Australasian Psychiatry: Bulletin of Royal Australian and New Zealand College of Psychiatrists
https://www.readbyqxmd.com/read/28830713/characterization-of-loperamide-mediated-block-of-herg-channels-at-physiological-temperature-and-its-proarrhythmia-propensity
#13
Jiansong Sheng, Phu N Tran, Zhihua Li, Sara Dutta, Kelly Chang, Thomas Colatsky, Wendy W Wu
BACKGROUND: Loperamide (Immodium®) is indicated for symptomatic control of diarrhea. It is a μ-opioid receptor agonist, and recently has been associated with misuse and abuse. At therapeutic doses loperamide has not been associated with cardiotoxicity. However, loperamide overdose is associated with proarrhythmia and death - two effects that are likely attributable to its block of cardiac ion channels that are critical for generating action potentials. In this study, we defined loperamide-hERG channel interaction characteristics, and used a ventricular myocyte action potential model to compare loperamide's proarrhythmia propensity to twelve drugs with defined levels of clinical risk...
August 19, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28828702/-intoxication-with-psychotropic-drugs
#14
R Bellmann, M Joannidis
Psychotropic drugs are medications that are indicated for treatment of psychiatric disorders. Attempted suicide is the major reason for intoxication but inadvertent overdosing may also occur. Other psychotropic agents are taken because of their stimulating and hallucinogenic effects and many have a high addictive potential. Poisoning is usually due to accidental overdosing. For treatment of benzodiazepine and opioid intoxication, flumazenil and naloxone, respectively, are used as specific antagonists. For intoxication by tricyclic antidepressants, sodium bicarbonate is the treatment of choice...
August 21, 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28817488/risk-management-of-hospitalized-psychiatric-patients-taking-multiple-qtc-prolonging-drugs
#15
Eline Vandael, Bert Vandenberk, Rik Willems, Johan Reyntens, Joris Vandenberghe, Veerle Foulon
PURPOSE/BACKGROUND: Drug-related QTc prolongation has been linked with Torsade de Pointes and sudden cardiac death. The objective of this study was to investigate the impact of starting an additional QTc-prolonging drug on the QTc interval of psychiatric inpatients. METHODS: An observational study was performed between May 2011 and December 2014 in 6 Belgian psychiatric hospitals. Inpatients who were already taking 1 QTc-prolonging drug or more could be included in the study when an additional QTc-prolonging drug was started...
August 16, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28813776/assessing-risk-factors-for-torsades-de-pointes
#16
Laura L Martin, Jodi R Heins
No abstract text is available yet for this article.
March 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28803378/qt-interval-prolongation-in-hospitalized-patients-on-cardiology-wards-a-prospective-observational-study
#17
Qasim Khan, Mohammad Ismail, Iqbal Haider, Inam Ul Haq, Sidra Noor
PURPOSE: Prolonged QT interval may lead to a lethal form of arrhythmia, torsades de pointes (TdP), which is associated with cardiovascular mortality. Therefore, we aimed to identify prevalence of QT interval prolongation, compare clinical characteristics of patients with normal and prolonged QT interval, and identify predictors of QT interval prolongation. METHODS: A prospective observational study was conducted in cardiology wards of two teaching hospitals in Pakistan...
August 12, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28801207/crediblemeds-org-what-does-it-offer
#18
REVIEW
Raymond L Woosley, Kristin Black, C William Heise, Klaus Romero
Since the 1990s, when numerous non-cardiac drugs were first recognized to have the potential to prolong the QT interval and cause torsades de pointes (TdP), clinicians, drug regulators, drug developers, and clinical investigators have become aware of the complexities of assessing evidence and determining TdP causality for the many drugs being marketed or under development. To facilitate better understanding, the Arizona Center for Education and Research on Therapeutics, known as AZCERT, has developed the CredibleMeds...
August 1, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28756335/computational-approaches-to-understand-the-adverse-drug-effect-on-potassium-sodium-and-calcium-channels-for-predicting-tdp-cardiac-arrhythmias
#19
Mohsen Sharifi
Ion channels play a crucial role in the cardiovascular system. Our understanding of cardiac ion channel function has improved since their first discoveries. The flow of potassium, sodium and calcium ions across cardiomyocytes is vital for regular cardiac rhythm. Blockage of these channels, delays cardiac repolarization or tend to shorten repolarization and may induce arrhythmia. Detection of drug risk by channel blockade is considered essential for drug regulators. Advanced computational models can be used as an early screen for torsadogenic potential in drug candidates...
July 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28755998/loperamide-induced-torsades-de-pointes-a-case-series
#20
Kenneth D Katz, Robert D Cannon, Matthew D Cook, Alexandra Amaducci, Ryan Day, Joshua Enyart, Glenn Burket, Lauren Porter, Timothy Roach, Jennifer Janssen, Karl E Williams
Loperamide is an over-the-counter, inexpensive, antidiarrheal opioid that can produce life-threatening toxicity at high concentrations. CASE REPORT 1: A 28-year-old man with a history of depression and substance abuse disorder (SUD) presented to the emergency department (ED) with shortness of breath and lightheadedness. He ingested large amounts of loperamide daily. The patient's initial electrocardiogram (ECG) demonstrated sinus rhythm, right axis deviation, undetectable PR interval, QRS 168 ms, and QTc 693 ms...
July 26, 2017: Journal of Emergency Medicine
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