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Drug-induced QTc interval prolongation

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https://www.readbyqxmd.com/read/27920831/assessment-of-drug-induced-proarrhythmias-due-to-pilsicainide-in-patients-with-atrial-tachyarrhythmias
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
Guillermo Alberto Keller, María Cecilia Villa Etchegoyen, Nicolás Fernández, Nancy Mónica Olivera, Patricia Noemí 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...
August 11, 2016: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27479699/levofloxacin-induced-qtc-prolongation-depends-on-the-time-of-drug-administration
#11
L Kervezee, V Gotta, J Stevens, W Birkhoff, Imc Kamerling, M Danhof, J H Meijer, J Burggraaf
Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in which 12 healthy male subjects received levofloxacin at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00. Using a pharmacokinetic-pharmacodynamic (PK-PD) modeling approach to account for variations in PKs, heart rate, and daily variation in baseline QT, we find that the concentration-QT relationship shows a 24-hour sinusoidal rhythm...
September 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27452340/influence-of-steroid-hormones-on-ventricular-repolarization
#12
Joe-Elie Salem, Joachim Alexandre, Anne Bachelot, Christian Funck-Brentano
QT interval prolongation, corrected for heart rate (QTc), either spontaneous or drug-induced, is associated with an increased risk of torsades de pointes and sudden death. Women have longer QTc than men and are at higher risk of torsades de pointes, particularly during post-partum and the follicular phase. Men with peripheral hypogonadism have longer QTc than healthy controls. The role of the main sex steroid hormones has been extensively studied with inconsistent findings. Overall, estradiol is considered to promote QTc lengthening while progesterone and testosterone shorten QTc...
July 22, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27434365/tp-te-interval-predicts-heart-rate-reduction-after-fingolimod-administration-in-patients-with-multiple-sclerosis
#13
Giuliano Tocci, Manuela Giuliani, Flaminia Canichella, Jacopo Timpano, Vivianne Presta, Pietro Francia, Maria Beatrice Musumeci, Federica Fubelli, Carlo Pozzilli, Massimo Volpe, Andrea Ferrucci
BACKGROUND: FTY720 (Fingolimod) is an immunosuppressive drug, which provides favourable effects in patients with multiple sclerosis (MS), albeit it induces heart rate (HR) and blood pressure (BP) reductions. Therefore, we tested potential factors able to predict HR response in MS patients treated with fingolimod. METHODS: We analysed patients with MS followed at our Neurology Outpatient Clinic from May 2013 to June 2015. All patients underwent BP measurements and 12-lead ECG before and 6-h after drug administration...
October 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27427789/pharmacokinetic-pharmacodynamic-modelling-of-drug-induced-qtc-interval-prolongation-in-man-prediction-from-in-vitro-human-ether-%C3%A3-go-go-related-gene-binding-and-functional-inhibition-assays-and-conscious-dog-studies
#14
V F S Dubois, E Casarotto, M Danhof, O Della Pasqua
BACKGROUND AND PURPOSE: Functional measures of human ether-à-go-go-related gene (hERG; Kv 11.1) channel inhibition have been prioritized as an in vitro screening tool for candidate molecules. However, it is unclear how these results can be translated to humans. Here, we explore how data on drug binding and functional inhibition in vitro relate to QT prolongation in vivo. Using cisapride, sotalol and moxifloxacin as paradigm compounds, we assessed the relationship between drug concentrations, binding, functional measures and in vivo effects in preclinical species and humans...
October 2016: British Journal of Pharmacology
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
#15
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/27262902/possibility-as-an-anti-cancer-drug-of-astemizole-evaluation-of-arrhythmogenicity-by-the-chronic-atrioventricular-block-canine-model
#16
Hiroko Izumi-Nakaseko, Yuji Nakamura, Xin Cao, Takeshi Wada, Kentaro Ando, Atsushi Sugiyama
Since astemizole in an oral dose of 50 mg/kg/day was recently reported to exert anti-cancer effect in mice, we evaluated its proarrhythmic potential using the atrioventricular block dogs in order to clarify its cardiac safety profile. An oral dose of 3 mg/kg prolonged the QT interval without affecting the QTc (n = 4), whereas that of 30 mg/kg increased the short-term variability of repolarization and induced premature ventricular contractions in each animal, resulting in the onset of torsade de pointes in 1 animal (n = 4)...
June 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27255383/histone-deacetylase-inhibitors-prolong-cardiac-repolarization-through-transcriptional-mechanisms
#17
Stan Spence, Mark Deurinck, Haisong Ju, Martin Traebert, LeeAnne McLean, Jennifer Marlowe, Corinne Emotte, Elaine Tritto, Min Tseng, Michael Shultz, Gregory S Friedrichs
Histone deacetylase (HDAC) inhibitors are an emerging class of anticancer agents that modify gene expression by altering the acetylation status of lysine residues of histone proteins, thereby inducing transcription, cell cycle arrest, differentiation, and cell death or apoptosis of cancer cells. In the clinical setting, treatment with HDAC inhibitors has been associated with delayed cardiac repolarization and in rare instances a lethal ventricular tachyarrhythmia known as torsades de pointes. The mechanism(s) of HDAC inhibitor-induced effects on cardiac repolarization is unknown...
September 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27212965/drug-induced-qt-interval-prolongation-and-torsades-de-pointes-role-of-the-pharmacist-in-risk-assessment-prevention-and-management
#18
REVIEW
James E Tisdale
Torsades de pointes (TdP) is a life-threatening arrhythmia associated with prolongation of the corrected QT (QTc) interval on the electrocardiogram. More than 100 drugs available in Canada, including widely used antibiotics, antidepressants, cardiovascular drugs and many others, may cause QTc interval prolongation and TdP. Risk factors for TdP include QTc interval >500 ms, increase in QTc interval ≥60 ms from the pretreatment value, advanced age, female sex, acute myocardial infarction, heart failure with reduced ejection fraction, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, treatment with diuretics and elevated plasma concentrations of QTc interval-prolonging drugs due to drug interactions, inadequate dose adjustment of renally eliminated drugs in patients with kidney disease and rapid intravenous administration...
May 2016: Canadian Pharmacists Journal: CPJ, Revue des Pharmaciens du Canada: RPC
https://www.readbyqxmd.com/read/27184113/management-of-chemotherapy-induced-nausea-and-vomiting-in-patients-receiving-multiple-day-highly-or-moderately-emetogenic-chemotherapy-role-of-transdermal-granisetron
#19
Flaminia Coluzzi, Consalvo Mattia
Granisetron transdermal delivery system (GTDS) is the first 5-HT3 drug to be transdermally delivered and represents a convenient alternative to oral and intravenous antiemetics for the treatment of chemotherapy-induced nausea and vomiting. GTDS is effective and well tolerated in patients receiving multiple-day moderate-to-highly emetogenic chemotherapy. In this setting noninferiority studies showed similar efficacy when GTDS was compared with intravenous and oral granisetron and intravenous palonosetron. GTDS has shown good cardiovascular safety; however, special caution is needed in patients at risk for developing excessive QTc interval prolongation and arrhythmias...
August 2016: Future Oncology
https://www.readbyqxmd.com/read/27167057/complex-influence-of-gonadotropins-and-sex-steroid-hormones-on-qt-interval-duration
#20
Guillaume Abehsira, Anne Bachelot, Fabio Badilini, Laurence Koehl, Martine Lebot, Clement Favet, Philippe Touraine, Christian Funck-Brentano, Joe-Elie Salem
CONTEXT: QT interval duration is longer in women than in men. Sex steroid hormones have inconsistently been suggested to explain this difference. The implication of gonadotropins has never been studied. OBJECTIVE: We report here the combined influence of sex steroid hormones and gonadotropins on QT interval duration in healthy subjects and patients with congenital adrenal hyperplasia (CAH) as a model of T and progesterone overexpression. DESIGN AND PATIENTS: Eighty-four CAH patients (58 women) and 84 healthy subjects matched and paired for sex and age were prospectively included...
July 2016: Journal of Clinical Endocrinology and Metabolism
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