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Torsades de Pointes

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https://www.readbyqxmd.com/read/29456831/early-afterdepolarisation-tendency-as-a-simulated-pro-arrhythmic-risk-indicator
#1
Beth McMillan, David J Gavaghan, Gary R Mirams
Drug-induced Torsades de Pointes (TdP) arrhythmia is of major interest in predictive toxicology. Drugs which cause TdP block the hERG cardiac potassium channel. However, not all drugs that block hERG cause TdP. As such, further understanding of the mechanistic route to TdP is needed. Early afterdepolarisations (EADs) are a cell-level phenomenon in which the membrane of a cardiac cell depolarises a second time before repolarisation, and EADs are seen in hearts during TdP. Therefore, we propose a method of predicting TdP using induced EADs combined with multiple ion channel block in simulations using biophysically-based mathematical models of human ventricular cell electrophysiology...
November 1, 2017: Toxicology Research
https://www.readbyqxmd.com/read/29441683/cardiovascular-safety-of-prokinetic-agents-a-focus-on-drug-induced-arrhythmias
#2
REVIEW
J R Giudicessi, M J Ackerman, M Camilleri
BACKGROUND: Gastrointestinal sensorimotor dysfunction underlies a wide range of esophageal, gastric, and intestinal motility and functional disorders that collectively constitute nearly half of all referrals to gastroenterologists. As a result, substantial effort has been dedicated toward the development of prokinetic agents intended to augment or restore normal gastrointestinal motility. However, the use of several clinically efficacious gastroprokinetic agents, such as cisapride, domperidone, erythromycin, and tegaserod, is associated with unfavorable cardiovascular safety profiles, leading to restrictions in their use...
February 14, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29433934/evidence-based-review-of-pharmacotherapy-for-acute-agitation-part-2-safety
#3
Leslie S Zun
BACKGROUND: The management of acute agitation in the emergency department often requires the administration of rapid-acting antipsychotic agents. However, there are few comparative studies and little guidance regarding the risks associated with use of such drugs in the acute setting. OBJECTIVE: This structured evidence-based review compared the safety of antipsychotic pharmacotherapies for acute agitation using data from randomized controlled trials identified by a literature search of the PubMed database...
February 9, 2018: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29427819/significance-of-t-wave-inversion-triggered-by-spontaneous-atrial-premature-beats-in-patients-with-long-qt-syndrome
#4
Nobuhiro Takasugi, Mieko Takasugi, Hiroko Goto, Takashi Kuwahara, Takashi Nakashima, Tomoki Kubota, Hiromitsu Kanamori, Masanori Kawasaki, Kazuhiko Nishigaki, Shinya Minatoguchi, Richard L Verrier
BACKGROUND: In patients with long QT syndrome (LQTS), a sudden increase in heart rate can cause T-wave alternans (TWA) with beat-to-beat alternating polarity of T wave. We hypothesized that LQTS patients at a high risk of Torsade de Pointes (TdP) may exhibit momentary atrial or sinoatrial premature beat-induced T-wave inversion (APB-TWI). OBJECTIVE: To assess the association of APB-TWI with TdP history and with microvolt TWA. METHODS: 24-h continuous 12-lead electrocardiograms (ECGs) were recorded in 18 healthy subjects and 39 consecutive patients with LQTS types 1 (n=21), 2 (n=4), 3 (n=4), and unidentified (n=10)...
February 7, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29424967/predicting-drug-induced-arrhythmias-by-multiscale-modeling
#5
F Sahli Costabal, J Yao, E Kuhl
Drugs often have undesired side effects. In the heart, they can induce lethal arrhythmias such as torsades de pointes. The risk evaluation of a new compound is costly and can take a long time, which often hinders the development of new drugs. Here we establish a high resolution, multiscale computational model to quickly assess the cardiac toxicity of new and existing drugs. The input of the model is the drug-specific current block from single cell electrophysiology; the output is the spatio-temporal activation profile and the associated electrocardiogram...
February 9, 2018: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/29424801/a-case-of-nonfatal-torsade-de-pointes-associated-with-psychiatric-polypharmacy
#6
Jonathan F Lister, Amanda L Torbett, Cassandra D Benge, Jennifer R Bean
No abstract text is available yet for this article.
February 8, 2018: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/29405316/acquired-long-qt-syndrome-and-torsade-de-pointes
#7
REVIEW
Nabil El-Sherif, Gioia Turitto, Mohamed Boutjdir
Since its initial description by Jervell and Lange-Nielsen in 19571 , the congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. Although congenital LQTS continues to remain the domain of cardiologists, cardiac electrophysiologists, and specialized centers, the by far more frequent acquired drug-induced LQTS is the domain of all physicians and other members of the health care team who are required to make therapeutic decisions. This report will review the electrophysiological mechanisms of LQTS and TdP, electrocardiographic (ECG) characteristics of acquired LQTS, its clinical presentation, management, and future directions in the field...
February 6, 2018: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/29380488/validation-and-clinical-utility-of-the-herg-ic50-cmax-ratio-to-determine-the-risk-of-drug-induced-torsades-de-pointes-a-meta-analysis
#8
David F Lehmann, William D Eggleston, Dongliang Wang
BACKGROUND: Use of the QT (QTc) interval on the electrocardiogram to predict torsades de pointes (TdP) risk from culprit drugs is neither sensitive nor specific. The ratio of the half-maximum inhibitory concentration of the hERG channel (hERG IC50) to the peak serum concentration of unbound drug (Cmax) is used during drug development to screen out chemical entities likely to cause TdP. PURPOSE: To validate the use of the hERG IC50/Cmax ratio to predict of TdP risk from a culprit drug by its correlation with TdP incidence...
January 30, 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/29377987/antiarrhythmic-effect-of-antazoline-in-experimental-models-of-acquired-short-and-long-qt-syndromes
#9
Christian Ellermann, Magdalena Sterneberg, Simon Kochhäuser, Dirk G Dechering, Michael Fehr, Lars Eckardt, Gerrit Frommeyer
Aims: Antazoline is a first-generation antihistamine with antiarrhythmic properties. This study examines potential electrophysiological effects of antazoline in short-QT-syndrome (SQTS) and long-QT-syndrome (LQTS). Methods and results: Sixty-five rabbit hearts were Langendorff-perfused. Action potential duration at 90% of repolarization (APD90), QT-interval, spatial dispersion (DISP), and effective refractory period (ERP) were measured. The IK, ATP-opener pinacidil (1 µM, n = 14) reduced APD90 (-14 ms, P < 0...
January 25, 2018: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/29372020/pain-medication-and-long-qt-syndrome
#10
REVIEW
Christoph Klivinyi, Helmar Bornemann-Cimenti
Long QT syndrome is a cardiac repolarization disorder and is associated with an increased risk of torsades de pointes. The acquired form is most often attributable to administration of specific medications and/or electrolyte imbalance. This review provides insights into the risk for QT prolongation associated with drugs frequently used in the treatment of chronic pain. In the field of pain medicine all the major drug classes (i.e. NSAIDs, opioids, anticonvulsive and antidepressant drugs, cannabinoids, muscle relaxants) contain agents that increase the risk of QT prolongation...
January 2018: Korean Journal of Pain
https://www.readbyqxmd.com/read/29332573/torsades-de-pointes-in-patients-with-polymyalgia-rheumatica
#11
Pietro Enea Lazzerini, Iacopo Bertolozzi, Maurizio Acampa, Rosella Fulceri, Franco Laghi-Pasini, Pier Leopoldo Capecchi
Polymyalgia rheumatica (PMR) represents the most common inflammatory rheumatic disease of the elderly. It is characterized by synovitis of proximal joints and extra-articular synovial structures, along with chronic high-grade systemic inflammation. PMR is closely related to giant cell arteritis (GCA), a large-vessel vasculitis that involves the major branches of the aorta, particularly the extracranial branches of carotid artery including temporal arteries. It is currently believed that PMR and GCA may represent different manifestations of the same disease process...
January 10, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29330129/estradiol-up-regulates-l-type-ca2-channels-via-membrane-bound-estrogen-receptor-phosphoinositide-3kinase-akt-camp-response-element-binding-protein-signaling-pathway
#12
Xiaoyan Yang, Xiaofang Mao, Gao Xu, Shasha Xing, Ansuman Chattopadhyay, Si Jin, Guy Salama
BACKGROUND: In long QT type-2 (LQT2), women are more prone to lethal arrhythmias called Torsade de Pointes (TdP) than men. We previously reported that 17-β-estradiol (E2) upregulates L-type Ca2+-channels and current (ICa,L) (∼30%) in rabbit ventricular myocytes by a classical genomic-mechanism mediated by estrogen-receptor-α (ER)α. In LQT2 ( IKr-blockade or bradycardia), the higher Ca2+ influx via ICa,L, causes Ca2+-overload, spontaneous sarcoplasmic reticulum Ca2+-release, and re-activation of ICa,L that trigger early afterdepolarizations (EADs) and TdP...
January 9, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29317399/effect-of-a-single-dose-of-i-v-ondansetron-on-qtc-interval-in-emergency-department-patients
#13
Kai Li, Kathy Vo, Byron K Lee, Newton Addo, Zlatan Coralic
PURPOSE: Results of a study to determine whether i.v. administration of a single dose of 4 mg of ondansetron was associated with QT interval prolongation in emergency department (ED) patients are reported. METHODS: In a prospective observational study conducted at an urban academic medical center ED, a convenience sample of adult ED patients treated with ondansetron 4 mg i.v. were enrolled. A 12-lead electrocardiogram (ECG) was obtained immediately before and 5 minutes after ondansetron administration...
January 9, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29298624/approach-to-initiating-qt-prolonging-oncology-drugs-in-the-ambulatory-setting
#14
Mário L de Lemos, Carrie Kung, Victoria Kletas, Nadine Badry, Isabell Kang
Since the introduction of regulatory drug approval guidance on the evaluation of QT interval prolongation, an increasing number of drug monographs has included cautions on the risk of QT prolongation. For example, QT prolongation is mentioned in the Canadian product monographs of 29 drugs commonly seen in oncology practice. This presents two major challenges. First, most guidelines and risk predictive tools for QT prolongation have been developed for hospitalized patients in acute care settings. In contrast, most QT-prolonging oncology drugs are used in medically stable patients in the ambulatory setting...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29297274/development-of-models-for-predicting-torsade-de-pointes-cardiac-arrhythmias-using-perceptron-neural-networks
#15
Mohsen Sharifi, Dan Buzatu, Stephen Harris, Jon Wilkes
BACKGROUND: Blockage of some ion channels and in particular, the hERG (human Ether-a'-go-go-Related Gene) cardiac potassium channel delays cardiac repolarization and can induce arrhythmia. In some cases it leads to a potentially life-threatening arrhythmia known as Torsade de Pointes (TdP). Therefore recognizing drugs with TdP risk is essential. Candidate drugs that are determined not to cause cardiac ion channel blockage are more likely to pass successfully through clinical phases II and III trials (and preclinical work) and not be withdrawn even later from the marketplace due to cardiotoxic effects...
December 28, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29283067/safety-limits-of-antidepressant-use-plus-combinations-focus-on-cardiovascular-function
#16
Florindo Stella, Julia C Loureiro, Marcos V Pais, Paulo R Canineu, Orestes V Florenza
BACKGROUND: Antidepressants have been widely prescribed for depression, anxiety, sleep disorders, and in the management of behavioural symptoms of adult-old patients. Although generally safe, newer generation antidepressants are not devoid of the risk of inducing clinically relevant adverse events. OBJECTIVES: To investigate the association between newer generation antidepressants and the occurrence of cardiovascular adverse events and electrocardiogram (ECG) abnormalities...
December 27, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29275963/qt-prolongation-torsades-de-pointes-and-psychotropic-medications-a-5-year-update
#17
REVIEW
Scott R Beach, Christopher M Celano, Alan M Sugrue, Caitlin Adams, Michael J Ackerman, Peter A Noseworthy, Jeff C Huffman
BACKGROUND: Some psychotropic medications have been associated with prolongation of the QT interval and QT prolongation, especially in those with medical illness, and are linked to lethal ventricular arrhythmias, such as Torsades de Pointes (TdP). In 2013, we published a review of QT prolongation, TdP, and psychotropic medications. OBJECTIVE: We provide an update over the past 5 years on the specific concerns most relevant to clinicians who see medically ill patients...
November 3, 2017: Psychosomatics
https://www.readbyqxmd.com/read/29274816/molecular-determinants-of-loperamide-and-n-desmethyl-loperamide-binding-in-the-herg-cardiac-k-channel
#18
Roy J Vaz, Jiesheng Kang, Yongyi Luo, David Rampe
Abuse of the common anti-diarrheal loperamide is associated with QT interval prolongation as well as development of the potentially fatal arrhythmia torsades de pointes. The mechanism underlying this cardiotoxicity is high affinity inhibition of the human ether-a-go-go-related gene (hERG) cardiac K+ channel. N-Desmethyl loperamide is the major metabolite of loperamide and is a close structural relative of the parent molecule. To date no information is available regarding the affinity of N-desmethyl loperamide for human cardiac ion channels...
December 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29259786/necessity-to-evaluate-pi3k-akt-signalling-pathway-in-proarrhythmia
#19
REVIEW
Martin Ezeani, Sunday Elom
The incidence of QT prolongation and torsades de pointes is on the rise due to the use of cardiovascular and non-cardiovascular drugs. Robust efforts have been made and are still ongoing to understand the underlying mechanisms that can enhance or prevent the development of drug-induced proarrhythmia. A caveat in the use of antiarrhythmic drugs is the ability to obtain safe action potential prolongation therapeutic effects, through IKr blockade. This remains as yet completely unachievable, as blockers of the potassium channel have not provided complete safe measures...
2017: Open Heart
https://www.readbyqxmd.com/read/29259513/torsades-de-pointes-after-ondansetron-infusion-in-2-patients
#20
Danny Y Lee, Tri Trinh, Sion K Roy
Drugs that prolong the electrocardiographic QT interval increase the risk of ventricular arrhythmias, particularly torsades de pointes. Ondansetron, a 5-hydroxytryptamine type 3 receptor antagonist antiemetic, is one such drug. We present the cases of 2 patients who were given intravenous ondansetron and subsequently developed torsades de pointes. Both had normal QT intervals at baseline but were discovered to have risk factors that predisposed them to drug-induced QT prolongation and ventricular arrhythmias...
October 2017: Texas Heart Institute Journal
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