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https://www.readbyqxmd.com/read/28808886/assessment-of-pharmacokinetic-interactions-between-obeticholic-acid-and-caffeine-midazolam-warfarin-dextromethorphan-omeprazole-rosuvastatin-and-digoxin-in-phase-1-studies-in-healthy-subjects
#1
Jeffrey E Edwards, Lise Eliot, Andrew Parkinson, Sharon Karan, Leigh MacConell
INTRODUCTION: Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters. METHODS: Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin)...
August 14, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28807352/unusual-digoxin-toxicity-with-myocardial-injury
#2
Mohamad Jihad Mansour, Maher Kalaoui, Elie Chammas, Omar Hamoui, Tarek Fawaz, Wael A AlJaroudi
A 38-year-old healthy male presented with vomiting and profuse diarrhea, associated with blurry and yellow coloration of the vision (xanthopsia). Laboratory workup was unremarkable, except for hyperkalemia (K 5.2 mEq/L) and mildly elevated troponin level 0.11 ng/mL (cut-off value 0.08). An electrocardiogram showed sinus bradycardia with deep scooping of the T waves. Although the patient denied intake of any drugs, herbs, consumption of plants, a digoxin level was drawn and was significantly elevated >5ng/mL (therapeutic range 0...
July 12, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28801325/aluminium-phosphide-poisoning-with-severe-cardiac-dysfunction-and-the-role-of-digoxin
#3
Khalid Hamid Changal, Muzamil Latief, Manzoor Parry, Farhat Abbas
Aluminium phosphide (ALP) is a common cause of suicidal poisoning in India where it is easily available and commonly known as 'rice tablet'. In rural areas of India, it is still used to protect rice and stored grains from rodents and pests. (1) There is no specific antidote for phosphide poisoning and treatment involves meticulous supportive care. Ingestion can lead to severe cardiac suppression and cardiogenic shock. For patients poisoned with ALP who continue to have refractory shock with persistent myocardial suppression despite the use of adrenergic inotropic agents, the addition of digoxin may be beneficial...
August 11, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28797721/intact-blood-brain-barrier-transport-of-small-molecular-drugs-in-animal-models-of-amyloid-beta-and-alpha-synuclein-pathology
#4
Sofia Gustafsson, Veronica Lindström, Martin Ingelsson, Margareta Hammarlund-Udenaes, Stina Syvänen
Pathophysiological impairment of the neurovascular unit, including the integrity and dynamics of the blood-brain barrier (BBB), has been denoted both a cause and consequence of neurodegenerative diseases. Pathological impact on BBB drug delivery has also been debated. The aim of the present study was to investigate BBB drug transport, by determining the unbound brain-to-plasma concentration ratio (Kp,uu,brain), in aged AβPP-transgenic mice, α-synuclein transgenic mice, and wild type mice. Mice were dosed with a cassette of five compounds, including digoxin, levofloxacin (1 mg/kg, s...
August 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28782051/comparison-of-digitalis-sensitivities-of-na-k-atpases-from-human-and-pig-kidneys
#5
Marjorie E Gable, Linda Ellis, Olga V Fedorova, Alexei Y Bagrov, Amir Askari
Digitalis drugs are selective inhibitors of the plasma membrane Na(+)/K(+)-ATPase. There are many studies on molecular mechanisms of digitalis interaction with purified pig kidney enzyme, with the tacit assumption that it is a good model of human kidney enzyme. However, previous studies on crude or recombinant human kidney enzymes are limited, and have not resulted in consistent findings on their digitalis sensitivities. Hence, we prepared comparably purified enzymes from human and pig kidneys and determined inhibitory constants of digoxin, ouabain, ouabagenin, bufalin, and marinobufagenin (MBG) on enzyme activity under optimal turnover conditions...
July 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28781802/sorafenib-induced-reversible-posterior-leukoencephalopathy-in-patients-with-renal-cell-carcinoma-a-report-of-two-cases
#6
Nobuki Furubayashi, Takahito Negishi, Hidenori Iwai, Kei Nagase, Motonobu Nakamura
Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare clinicoradiological syndrome that is characterized by neurological symptoms, including seizures, headaches, visual abnormalities, confusion and encephalopathy, accompanied by vasogenic edema of the posterior white matter observed on neuroimaging. Sorafenib is an inhibitor of pro-angiogenic receptor tyrosine kinases, such as vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and vascular endothelial growth factor receptor 3...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28755414/successful-use-of-digoxin-specific-immune-fab-in-the-treatment-of-severe-nerium-oleander-toxicosis-in-a-dog
#7
Amaris Pao-Franco, Tara N Hammond, Linda K Weatherton, Camille DeClementi, Scott D Forney
OBJECTIVE: To describe a case in which digoxin-specific immune Fab was used successfully in a dog with severe oleander toxicosis secondary to ingesting plant material. CASE SUMMARY: A 6-year-old intact female Rhodesian Ridgeback mixed breed dog was presented for severe oleander toxicosis and was refractory to all antiarrhythmic therapies and supportive care. Digoxin-specific immune Fab was successful in treating this dog. The dog recovered but suffered ischemic injuries, the long-term effects of which are unknown...
July 29, 2017: Journal of Veterinary Emergency and Critical Care
https://www.readbyqxmd.com/read/28753733/lost-in-translation-no-effect-of-a-high-profile-publication-on-the-concomitant-use-of-interacting-drugs
#8
Emily K Acton, Charles E Leonard, Warren B Bilker, Shobha Phansalkar, Sean Hennessy
We sought to assess whether a high-profile publication that demonstrated serious clinical consequences of specific drug-drug interactions (DDIs) reduced the concomitant use of those drugs. We conducted a quasi-experimental study using 2000-2008 prescription claims from a commercial health insurer to examine trends in the dispensing of the interacting drug pairs (angiotensin-converting enzyme inhibitors[ACEI] + potassium-sparing diuretic, digoxin + clarithromycin, and glyburide + cotrimoxazole) and control drug pairs previously reported in a top-tier general medicine journal...
July 28, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28750542/clinical-presentation-predictors-and-outcomes-among-mineralocorticoid-receptor-antagonist-mra-eligible-acute-heart-failure-patients-in-the-heart-function-assessment-registry-trial-in-saudi-arabia-hearts
#9
Mostafa Q AlShamiri, Khalid F AlHabib, Waleed AlHabeeb, Ismail R Raslan, Anhar Ullah, Abdelfatah A Elasfar, Fayez Alshaer, Hanan Albackr, Layth Mimish, Ali Almasood, Saleh AlGhamdi, Abdullah Ghabashi
Mineralocorticoid receptor antagonist (MRA) therapy is indicated after myocardial infarction in patients with acute heart failure (AHF) with an ejection fraction ≤40% and lacking contraindications. We analyzed clinical presentations, predictors, and outcomes of MRA-eligible patients within a prospective registry of patients with AHF from 18 hospitals in Saudi Arabia, from 2009 to 2010. For this subgroup, mortality rates were followed until 2013, and the clinical characteristics, management, predictors, and outcomes were compared between MRA-treated and non-MRA-treated patients...
January 1, 2017: Angiology
https://www.readbyqxmd.com/read/28729311/a-review-of-rate-control-in-atrial-fibrillation-and-the-rationale-and-protocol-for-the-rate-af-trial
#10
Dipak Kotecha, Melanie Calvert, Jonathan J Deeks, Michael Griffith, Paulus Kirchhof, Gregory Yh Lip, Samir Mehta, Gemma Slinn, Mary Stanbury, Richard P Steeds, Jonathan N Townend
BACKGROUND AND OBJECTIVE: Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article , we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity...
July 20, 2017: BMJ Open
https://www.readbyqxmd.com/read/28727807/digoxin-reveals-a-functional-connection-between-hiv-1-integration-preference-and-t-cell-activation
#11
Alexander Zhyvoloup, Anat Melamed, Ian Anderson, Delphine Planas, Chen-Hsuin Lee, Janos Kriston-Vizi, Robin Ketteler, Andy Merritt, Jean-Pierre Routy, Petronela Ancuta, Charles R M Bangham, Ariberto Fassati
HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28720385/differences-of-lipid-membrane-modulation-and-oxidative-stress-by-digoxin-and-21-benzylidene-digoxin
#12
Lilian Nd Silva, Silmara Lg Alves, Jessica Venugopal, Vanessa F Cortes, Herica L Santos, José Afp Villar, Leandro A Barbosa
Cardiotonic steroids (CTS) are compounds which bind to the Na,K-ATPase, leading to its inhibition and in some cases initiating signaling cascades. Long utilized as a treatment for congestive heart disease, CTS have more recently been observed to inhibit proliferation and cause apoptosis in several cancer cell lines. A synthetic derivative of the CTS digoxin, called 21-benzylidene digoxin (21-BD), activates the Na,K-ATPase rather than cause its inhibition, as its parent compound does. Here, the mechanism behind the unique effects of 21-BD are further explored...
July 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28720014/the-impact-of-intrauterine-treatment-on-fetal-tachycardia-a-nationwide-survey-in-japan
#13
Keiko Ueda, Yasuki Maeno, Takekazu Miyoshi, Noboru Inamura, Motoyoshi Kawataki, Mio Taketazu, Masaki Nii, Akiko Hagiwara, Hitoshi Horigome, Makio Shozu, Wataru Shimizu, Satoshi Yasukochi, Hitoshi Yoda, Isao Shiraishi, Heima Sakaguchi, Shinji Katsuragi, Haruhiko Sago, Tomoaki Ikeda
OBJECTIVES: To investigate the clinical course of fetal tachycardia and analyze the impact of intrauterine treatment on the postnatal treatment and patient outcomes. STUDY DESIGN: This was a retrospective review of cases of fetal tachycardia that occurred from 2004 to 2006. Data were collected from questionnaires that were sent to all 750 secondary or tertiary perinatal care centers in Japan. RESULTS: Eighty-two cases (14 with fetal hydrops) were analyzed (supraventricular tachycardia [SVT], n = 52; atrial flutter [AFL], n = 23; and ventricular tachycardia, n = 7)...
July 19, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28711269/development-of-an-isothermal-amplification-based-assay-for-the-rapid-visual-detection-of-salmonella-bacteria
#14
Hai-Bin Liu, Yu-Xuan Zang, Xin-Jun Du, Ping Li, Shuo Wang
The efficient and timely detection of pathogens is a major concern worldwide. The aim of this study was to establish a rapid detection method for Salmonella bacteria in food samples to facilitate timely treatment. Widely used detection methods currently include culture-based methods and PCR-based methods. The former are time consuming, requiring 2 to 3 d, whereas the latter have higher accuracy but are typically complicated, requiring expertise and expensive instruments. In this study, a sensitive and rapid approach for the visual and point-of-use detection of Salmonella bacteria based on recombinase polymerase amplification (RPA) and a lateral-flow (LF) nucleic acid strip was established...
September 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28706279/elimination-of-undifferentiated-human-embryonic-stem-cells-by-cardiac-glycosides
#15
Yu-Tsen Lin, Cheng-Kai Wang, Shang-Chih Yang, Shu-Ching Hsu, Hsuan Lin, Fang-Pei Chang, Tzu-Chien Kuo, Chia-Ning Shen, Po-Ming Chiang, Michael Hsiao, Frank Leigh Lu, Jean Lu
An important safety concern in the use of human pluripotent stem cells (hPSCs) is tumorigenic risk, because these cells can form teratomas after an in vivo injection at ectopic sites. Several thousands of undifferentiated hPSCs are sufficient to induce teratomas in a mouse model. Thus, it is critical to remove all residue-undifferentiated hPSCs that have teratoma potential before the clinical application of hPSC-derived cells. In this study, our data demonstrated the cytotoxic effects of cardiac glycosides, such as digoxin, lanatoside C, bufalin, and proscillaridin A, in human embryonic stem cells (hESCs)...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701029/high-risk-prescribing-in-an-irish-primary-care-population-trends-and-variation
#16
Catherine J Byrne, Caitriona Cahir, Carmel Curran, Kathleen Bennett
AIMS: To examine the prevalence of high-risk prescribing (HRP) in community-dwelling adults in Ireland from 2011-2015 using consensus-validated indicators, factors associated with HRP, and variation in HRP between general practitioners (GPs) and dispensing of high-risk prescriptions between pharmacies. METHODS: A repeated cross-sectional national pharmacy claims database study. Prescribing indicators were based on those developed in formal consensus studies and applicable to pharmacy claims data...
July 12, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28693242/bufalin-sensitizes-human-bladder-carcinoma-cells-to-trail-mediated-apoptosis
#17
Kyung-Hwa Kang, Min Ho Han, Jin-Woo Jeong, Cheol Park, Sang-Hyup Lee, Hai Woong Lee, Sang Hoon Hong, Yung Hyun Choi, Su Hyun Hong
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, has garnered interest as it is relatively non-toxic to normal cells, but selectively induces apoptotic cell death in multiple types of transformed or malignant cells. Bufalin is the major digoxin-like immunoreactive component of Sum Su, which is obtained from the skin and parotid venom gland of the toad. Bufalin is known to inhibit cell proliferation and induce apoptosis in a variety of cancer cells. The present study investigated whether bufalin promoted TRAIL-induced apoptotic cell death...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28692216/-digoxin-and-atrial-fibrillation-in-2016
#18
Sarah Théone, Sebastian Carballo, David Carballo, Christophe Marti
Various properties of digoxin have been exploited for decades, amongst which are its positive inotropy used in the treatment of heart failure, and its vagotonic effect used to slow ventricular response to atrial fibrillation. Pharmacologic properties of digoxin are however characterised by a narrow therapeutic interval, and recent observational studies suggest a potential association with increased mortality in patients with atrial fibrillation. As a result and because of available alternative therapeutic strategies, current guidelines do not recommend digoxin as first line treatment of atrial fibrillation...
October 19, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28688145/therapeutic-concentrations-of-digitoxin-inhibit-endothelial-focal-adhesion-kinase-and-angiogenesis-induced-by-diverse-growth-factors
#19
Annalisa Trenti, Elisabetta Zulato, Lorenza Pasqualini, Stefano Indraccolo, Chiara Bolego, Lucia Trevisi
BACKGROUND AND PURPOSE: Cardiac glycosides are Na(+) /K(+) -ATPases inhibitors used to treat congestive heart failure and cardiac arrhythmias. Epidemiological studies indicate that patients on digitalis therapy are more protected from cancer. Evidence of a selective cytotoxicity against cancer cells has suggested their potential use as anticancer drugs. The effect on angiogenesis of clinically used cardiac glycosides has not been extensively explored. EXPERIMENTAL APPROACH: We studied the effect of digoxin, digitoxin and ouabain on early events of the angiogenic process in human umbilical vein endothelial cells (HUVEC)...
July 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28685495/effects-of-metformin-and-furosemide-on-rosuvastatin-pharmacokinetics-in-healthy-volunteers-implications-for-their-use-as-probe-drugs-in-a-transporter-cocktail
#20
Peter Stopfer, Thomas Giessmann, Kathrin Hohl, Ashish Sharma, Naoki Ishiguro, Mitchell E Taub, Arvid Jungnik, Dietmar Gansser, Thomas Ebner, Fabian Müller
BACKGROUND: In a recently described probe drug cocktail for clinically relevant drug transporters containing digoxin, furosemide, metformin and rosuvastatin, mutual interactions were essentially absent except for increases in the systemic exposure of rosuvastatin. To optimize the cocktail, we further examined the dose dependence of the effects of metformin and furosemide on rosuvastatin pharmacokinetics. METHODS: This was a randomized, open label, single center, six-treatment, six-period, six-sequence crossover trial...
July 6, 2017: European Journal of Drug Metabolism and Pharmacokinetics
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