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https://www.readbyqxmd.com/read/28803378/qt-interval-prolongation-in-hospitalized-patients-on-cardiology-wards-a-prospective-observational-study
#1
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
#2
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/28799823/lack-of-qt-prolongation-for-2-o-methoxyethyl-modified-antisense-oligonucleotides-based-on-retrospective-exposure-response-analysis-of-ten-phase-1-dose-escalation-placebo-controlled-studies-in-healthy-subjects
#3
Rosie Z Yu, Rudy Gunawan, Richard S Geary, Steven G Hughes, Scott P Henry, Yanfeng Wang
The potential of QT prolongation of ten 2'-O-methoxyethyl-modified (2'-MOE) antisense oligonucleotides (ASOs) was evaluated retrospectively via exposure/response (ER) analysis using data from Phase 1 clinical studies in healthy subjects. All Phase 1 studies were double-blind, placebo-controlled, single and multiple ascending dose studies designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of the ASOs in healthy subjects. The active doses in these studies ranged from 50 to 450 mg administered by subcutaneous (SC) injection in single and multiple ascending dose cohorts...
August 11, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28797793/bpc-157-counteracts-qtc-prolongation-induced-by-haloperidol-fluphenazine-clozapine-olanzapine-quetiapine-sulpiride-and-metoclopramide-in-rats
#4
Dean Strinic, Zeljka Belosic Halle, Kresimir Luetic, Ana Nedic, Igor Petrovic, Mario Sucic, Gordana Zivanovic Posilovic, Dijana Balenovic, Sanja Strbe, Mario Udovicic, Domagoj Drmic, Mirjana Stupnisek, Martina Lovric Bencic, Sven Seiwerth, Predrag Sikiric
AIM: Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. MAIN METHODS: To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10μg, 10ng/kg ip) immediately after each administrations of haloperidol (0...
August 7, 2017: Life Sciences
https://www.readbyqxmd.com/read/28793999/association-of-qt-prolonging-medication-use-in-ckd-with-electrocardiographic-manifestations
#5
Soren Snitker, Rebecca M Doerfler, Elsayed Z Soliman, Rajat Deo, Wendy L St Peter, Susan Kramlik, Michael J Fischer, Sankar Navaneethan, Patrice Delafontaine, Bernard G Jaar, Akinlolu Ojo, Gail K Makos, Anne Slaven, Matthew R Weir, Min Zhan, Jeffrey C Fink
BACKGROUND AND OBJECTIVES: Several drugs used in CKD can prolong electrocardiographic conduction. We examined the use of electrocardiogram QT-prolonging medications in predialysis CKD and their association with QT duration. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 3252 Chronic Renal Insufficiency Cohort participants with at least one study electrocardiogram between 2003 and 2011 were included. QT-prolonging medications used in 100 or more visits (n=16,451 visits) along with diuretics and proton pump inhibitors, given their potential for electrolyte disturbances, were examined for QT interval prolongation...
August 9, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28791627/influence-of-intravenous-administration-of-the-antipsychotic-drug-benperidol-on-the-qt-interval
#6
Alexander Schmidt, Peter Fischer, Beate Wally, Joachim Scharfetter
A group effect is generally assumed regarding the prolongation of the QT interval through butyrophenone antipsychotics like haloperidol. Consequently intravenous administration of benperidol is seen critically notwithstanding sparse evidence; thus benperidol and haloperidol were compared regarding their cardiac risk of prolonging the QT interval when administered intravenously for acute sedation of psychotic patients. The QT interval was measured by a 12-lead ECG. For the correction of QT values Bazett's formula was used...
August 8, 2017: Neuropsychiatrie: Klinik, Diagnostik, Therapie und Rehabilitation
https://www.readbyqxmd.com/read/28780600/the-anti-influenza-drug-oseltamivir-reduces-atrial-fibrillation-in-an-experimental-whole-heart-model
#7
Gerrit Frommeyer, André Mittelstedt, Julian Wolfes, Christian Ellermann, Simon Kochhäuser, Patrick Leitz, Dirk G Dechering, Lars Eckardt
Recent experimental studies suggested direct effects of the anti-influenza drug oseltamivir on cardiac electrophysiology. We therefore aimed at analyzing potential antiarrhythmic effects of oseltamivir on atrial fibrillation (AF) in an experimental whole-heart model. Twelve rabbit hearts were isolated and Langendorff perfused. Thereafter, hearts were paced at cycle lengths of 350, 250, and 200 ms in the atrium. A standardized protocol employing atrial burst pacing induced AF in 4 of 12 hearts under baseline conditions (33%, 11 episodes)...
August 6, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28770276/a-comparative-study-of-qt-prolongation-with-serotonin-reuptake-inhibitors
#8
Ana Ojero-Senard, Justine Benevent, Emmanuelle Bondon-Guitton, Geneviève Durrieu, Leila Chebane, Melanie Araujo, Francois Montastruc, Jean-Louis Montastruc
BACKGROUND: QT interval prolongations were described with citalopram and escitalopram. However, the effects of the other serotonin reuptake inhibitors (SRIs) remained discussed. In order to identify a putative signal with other SRIs, the present study investigates the reports of QT interval prolongation with SRIs in two pharmacovigilance databases (PVDB). METHODS: Two kinds of investigations were performed: (1) a comparative study in VigiBase®, the WHO PVDB, where notifications of QT prolongation with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were selected...
August 3, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28766238/magnesium-isoglycyrrhizinate-inhibits-l-type-ca-2-channels-ca-2-transients-and-contractility-but-not-herg-k-channels
#9
Yue Lin, Yuanyuan Zhang, Qiongtao Song, Tao Song, Xue Han, Ying Zhang, Xuan Zhang, Xi Chu, Fenghua Zhang, Li Chu, Jianping Zhang
To explore the cardiovascular protective effects of Magnesium isoglycyrrhizinate (MI), especially the underlying cellular mechanisms related to L-type calcium channels and myocardial contractility, and to examine the effects of MI on hERG K(+) current expressed in HEK293 cells. We used the whole-cell patch clamp technique, video-based edge detection and dual excitation fluorescence photomultiplier systems to explore the effect of MI on L-type Ca(2+) currents (ICa-L) and cell contraction in rat cardiomyocytes...
August 1, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28762476/use-of-early-clinical-trial-data-to-support-thorough-qt-study-waiver-for-upadacitinib-and-utility-of-food-effect-to-demonstrate-ecg-assay-sensitivity
#10
Mohamed-Eslam F Mohamed, Jiewei Zeng, Ping Jiang, Balakrishna Hosmane, Ahmed A Othman
Exposure-response analyses of QT data from early-stage clinical studies represent a valuable tool to assess the QT prolongation potential for drugs in development in lieu of stand-alone thorough QT (TQT) studies. However, demonstrating adequate ECG assay sensitivity can be challenging in the absence of a positive pharmacological control. Upadacitinib is a Janus Kinase 1 inhibitor currently being evaluated in Phase 3 rheumatoid arthritis trials. Exposure-response analyses to evaluate the QT prolongation potential for upadacitinib from Phase 1 trials and the utility of the effect of food on QTcF to demonstrate ECG assay sensitivity are presented...
August 1, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28758888/bedaquiline-and-delamanid-combination-treatment-of-5-patients-with-pulmonary-extensively-drug-resistant-tuberculosis
#11
Andrey Maryandyshev, Emanuele Pontali, Simon Tiberi, Onno Akkerman, Shashank Ganatra, Tsetan Dorji Sadutshang, Jan-Willem Alffenaar, Rohit Amale, Jai Mullerpattan, Sonam Topgyal, Zarir Farokh Udwadia, Rosella Centis, Lia D'Ambrosio, Giovanni Sotgiu, Giovanni Battista Migliori
We report the experiences of 5 patients taking bedaquiline with delamanid in combination: 1 patient was cured; 3 culture converted, with 2 continuing and 1 changing therapy; and 1 died from respiratory insufficiency. For 2 patients, QT-interval prolongation but no arrhythmias occurred. Use of this therapy is justified for patients with limited options.
October 15, 2017: Emerging Infectious Diseases
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
#12
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/28751260/identification-of-appropriate-qtc-formula-in-beagle-dogs-for-nonclinical-safety-assessment
#13
Shitalkumar Patel, Laxit Bhatt, Rajesh Patel, Chitrang Shah, Vipul Patel, Jitendra Patel, Rajesh Sundar, Upendra Bhatnagar, Mukul Jain
A number of drugs belonging to different therapeutic classes cause increase in QT interval duration, and this change has been associated with ventricular arrhythmias. Investigation of changes in QT intervals in toxicity studies in dogs is therefore of potential value. Estimation of a direct effect of drugs on the duration of the QT interval can be confused by drug-induced increases in heart rate. The objective of this evaluation was to identify an appropriate correction formula by comparing different formulae that could appropriately correct changes in QT interval in conscious beagle dogs in toxicology studies...
July 25, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28748465/automated-patch-clamp-methods-for-the-herg-cardiac-potassium-channel
#14
Sylvie Houtmann, Brigitte Schombert, Camille Sanson, Michel Partiseti, G Andrees Bohme
The human Ether-a-go-go Related Gene (hERG) product has been identified as a central ion channel underlying both familial forms of elongated QT interval on the electrocardiogram and drug-induced elongation of the same QT segment. Indeed, reduced function of this potassium channel involved in the repolarization of the cardiac action potential can produce a type of life-threatening cardiac ventricular arrhythmias called Torsades de Pointes (TdP). Therefore, hERG inhibitory activity of newly synthetized molecules is a relevant structure-activity metric for compound prioritization and optimization in medicinal chemistry phases of drug discovery...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28746337/genome-wide-analysis-of-ivermectin-response-by-onchocerca-volvulus-reveals-that-genetic-drift-and-soft-selective-sweeps-contribute-to-loss-of-drug-sensitivity
#15
Stephen R Doyle, Catherine Bourguinat, Hugues C Nana-Djeunga, Jonas A Kengne-Ouafo, Sébastien D S Pion, Jean Bopda, Joseph Kamgno, Samuel Wanji, Hua Che, Annette C Kuesel, Martin Walker, Maria-Gloria Basáñez, Daniel A Boakye, Mike Y Osei-Atweneboana, Michel Boussinesq, Roger K Prichard, Warwick N Grant
BACKGROUND: Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28730460/impact-of-safety-warnings-on-domperidone-prescribing-in-ireland
#16
M Teeling, M J MacAvin, K Bennett
AIM: This study aimed to investigate the impact of the 2014 safety warnings on use of domperidone, on subsequent prescribing patterns in Ireland. METHODS: The Irish HSE-PCRS pharmacy claims database was used to identify the study cohort (aged 18+), prescribed domperidone from Jan 2014 to Oct 2015. Dosage was available for each claim; concomitant prescription with the following drug classes was identified and calculated as a percentage of the total number of claims: anti-arrhythmics, macrolide antimicrobials and the selective serotonin receptor inhibitors (SSRIs) citalopram and escitalopram...
July 20, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28728494/the-clinical-significance-of-qt-prolongation-associated-with-tamoxifen-a-review-of-the-literature
#17
Katherine Fung, Julia Imeson, Frances Cusano
Objective To review the literature discussing QT prolongation associated with the use of tamoxifen in order to evaluate the clinical significance. Data sources A search of PubMed (1946 to 2017), MEDLINE (1946 to 2017) and EMBASE (1947 to 2017) was performed using a combination of the following search terms: tamoxifen, estrogen antagonist, selective estrogen receptor modulator, QT prolongation, QT interval, long QT syndrome and torsades de pointes. All searches were limited to human subjects. Reference lists of the literature found were also reviewed but did not reveal any further articles...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28714380/loperamide-and-cardiac-events-is-high-dose-use-still-safe-for-chemotherapy-induced-diarrhea
#18
Mário L de Lemos, Jolene Guenter, Victoria Kletas
High-dose loperamide is often used for the acute management of chemotherapy-induced diarrhea, with a maximum daily dosing of up to 24 mg. Recently, the US Food and Drug Administration has issued a warning that loperamide can cause rare serious cardiac events, including QT prolongation, torsades de pointes, cardiac arrest and death. Most events were reported in patients taking very high doses for an extended period of time. Daily intake ranged from 64 mg to 1600 mg, often continuously for weeks or months...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28713157/population-pharmacokinetics-of-moxifloxacin-and-its-concentration-qt-interval-relationship-modeling-in-chinese-healthy-volunteers
#19
Feng-Yan Xu, Ji-Han Huang, Ying-Chun He, Li-Yu Liang, Lu-Jin Li, Juan Yang, Fang Yin, Ling Xu, Qing-Shan Zheng, Kun Wang
Moxifloxacin (MX) is an 8-methoxyquinolone antimicrobial drug, which is often used as a positive control in thorough QT (TQT) studies. In the present study we established the population pharmacokinetics model of MX and the relationship of MX concentrations with the QT and various corrected QT (QTc) intervals, and compared the results with other ethnicities. The MX data used for modeling were obtained from a published TQT interval prolongation study of antofloxacin with MX as the positive control. In this four-period crossover study, 24 adult Chinese healthy volunteers received either 200 or 400 mg of oral antofloxacin once daily, 400 mg of MX, or a placebo...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28711156/towards-a-structural-view-of-drug-binding-to-herg-k-channels
#20
REVIEW
Jamie I Vandenberg, Eduardo Perozo, Toby W Allen
The human ether-a-go-go-related gene (hERG) K(+) channel is of great medical and pharmaceutical relevance. Inherited mutations in hERG result in congenital long-QT syndrome which is associated with a markedly increased risk of cardiac arrhythmia and sudden death. hERG K(+) channels are also remarkably susceptible to block by a wide range of drugs, which in turn can cause drug-induced long-QT syndrome and an increased risk of sudden death. The recent determination of the near-atomic resolution structure of the hERG K(+) channel, using single-particle cryo-electron microscopy (cryo-EM), provides tremendous insights into how these channels work...
July 12, 2017: Trends in Pharmacological Sciences
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