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Cardiovascular pharmacogenetics

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https://www.readbyqxmd.com/read/28919802/abcb1-and-abcc1-single-nucleotide-polymorphisms-in-patients-treated-with-clozapine
#1
Irina Piatkov, Dorgival Caetano, Yolinda Assur, Sue Lynn Lau, Trudi Jones, Steven C Boyages, Mark McLean
Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and intracellular membranes, including the blood-brain barrier. Genetic variations in these proteins can account for differences in treatment response. We investigated the influence of ABCB1 rs1045642 and ABCC1 rs212090 single-nucleotide polymorphisms (SNPs) on CZ serum level, clinical outcome, and changes in body mass index (BMI) in the first year of CZ treatment...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28892404/mechanisms-underlying-metabolic-disturbances-associated-with-psychosis-and-antipsychotic-drug-treatment
#2
Gavin P Reynolds, Olga O McGowan
The increase in cardiovascular disease and reduced life expectancy in schizophrenia likely relate to an increased prevalence of metabolic disturbances. Such metabolic risk factors in schizophrenia may result from both symptom-related effects and aetiological factors. However, a major contributory factor is that of treatment with antipsychotic drugs. These drugs differ in effects on body weight; the underlying mechanisms are not fully understood and may vary between drugs, but may include actions at receptors associated with the hypothalamic control of food intake...
August 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28882537/bevacizumab-induced-hypertension-clinical-presentation-and-molecular-understanding
#3
REVIEW
Megan Li, Deanna L Kroetz
Bevacizumab is a vascular endothelial growth factor-A-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of several types of cancer. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy and lead to other cardiovascular complications. The factors that contribute to interindividual variability in blood pressure response to bevacizumab treatment are not well understood. In this review, we outline research efforts to understand the mechanisms and pathophysiology of hypertension resulting from bevacizumab treatment...
September 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28817866/genomic-medicine-in-primary-care
#4
Catherine Hajek
Genomic medicine is a powerful tool with great potential to improve outcomes in the primary care setting. From a broad perspective, genomic medicine can be applied to rare disease, common disease and pharmacogenetics. There are applications in which it can be used to better identify rare disease, improve screening for common disease, reduce adverse drug effects and help to identify the right medication more quickly. This article provides specific examples of clinical applications for genomic medicine in the realm of cardiovascular disease to provide a better understanding of its potential use in primary care...
2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28753643/pharmacogenetic-meta-analysis-of-baseline-risk-factors-pharmacodynamic-efficacy-and-tolerability-endpoints-from-two-large-global-cardiovascular-outcomes-trials-for-darapladib
#5
Astrid Yeo, Li Li, Liling Warren, Jennifer Aponte, Dana Fraser, Karen King, Kelley Johansson, Allison Barnes, Colin MacPhee, Richard Davies, Stephanie Chissoe, Elizabeth Tarka, Michelle L O'Donoghue, Harvey D White, Lars Wallentin, Dawn Waterworth
Darapladib, a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, failed to demonstrate efficacy for the primary endpoints in two large phase III cardiovascular outcomes trials, one in stable coronary heart disease patients (STABILITY) and one in acute coronary syndrome (SOLID-TIMI 52). No major safety signals were observed but tolerability issues of diarrhea and odor were common (up to 13%). We hypothesized that genetic variants associated with Lp-PLA2 activity may influence efficacy and tolerability and therefore performed a comprehensive pharmacogenetic analysis of both trials...
2017: PloS One
https://www.readbyqxmd.com/read/28745551/institutional-profile-of-pharmacogenetics-within-university-of-michigan-college-of-pharmacy
#6
Daniel L Hertz, Jasmine A Luzum, Amy L Pasternak, Kristen M Ward, Hao-Jie Zhu, James M Rae, Vicki L Ellingrod
The University of Michigan College of Pharmacy has made substantial investment in the area of pharmacogenomics to further bolster its activity in pharmacogenomics research, implementation and education. Four tenure-track faculty members have active research programs that focus primarily on the discovery of functional polymorphisms (HJ Zhu), and genetic associations with treatment outcomes in patients with cancer (DL Hertz), cardiovascular disease (JA Luzum) and psychiatric conditions (VL Ellingrod). Recent investments from the University and the College have accelerated the implementation of pharmacogenetics broadly across the institution and in targeted therapeutic areas...
July 26, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28672099/impact-of-pharmacogenetics-on-efficacy-and-safety-of-statin-therapy-for-dyslipidemia
#7
REVIEW
Whitney D Maxwell, Laura B Ramsey, Samuel G Johnson, Kate G Moore, Michael Shtutman, John H Schoonover, Marina Kawaguchi-Suzuki
Interindividual variability in response to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, with regard to both efficacy and safety is an obvious target for pharmacogenetic research. Many genes have been identified as possible contributors to variability in statin response and safety. Genetic polymorphisms may alter the structure or expression of coded proteins, with potential impacts on lipid and statin absorption, distribution, metabolism, and elimination as well as response pathways related to the pharmacologic effect...
July 3, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28654154/commentary-should-pharmacogenomic-evidence-be-considered-in-clinical-decision-making-focus-on-select-cardiovascular-drugs
#8
Michael B Bottorff, David R Bright, David F Kisor
Despite advances in technology and guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) that focus on how to use pharmacogene test results, hurdles remain that have delayed the widespread application of pharmacogenomics in clinical practice. These hurdles include a lack of prospective randomized controlled trials to address the utility of pharmacogenomics on clinical outcomes, what the clinical algorithm for pharmacogenomics should be, and whether pharmacogenomics is cost-effective...
September 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28611364/association-of-polymorphisms-in-pharmacogenetic-candidate-genes-with-propofol-susceptibility
#9
Qi Zhong, Xiangdong Chen, Yan Zhao, Ru Liu, Shanglong Yao
Significant individual susceptibility to intravenous anesthetic propofol exists. The etiology of individual variability in the response to propofol may be influenced by genetic polymorphisms in metabolic and functional pathways. With current pharmacogenetics and modern molecular biology technologies, it is possible to study the influence of genetic polymorphisms on susceptibility to propofol. When inducing general anesthesia with intravenous propofol, high individual susceptibility to propofol was found. Using Sequenom MassARRAY single-nucleotide polymorphism (SNP) genotyping, we identified a mutation (rs6313) in the 5HT2A gene that was correlated to individual susceptibility to propofol effect-site concentration (Cep) and onset time of propofol induction...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592969/corrigendum-to-pharmacogenetics-of-risperidone-and-cardiovascular-risk-in-children-and-adolescents
#10
Amilton Dos Santos-Júnior, Taciane Barbosa Henriques, Maricilda Palandi de Mello, Osmar Henrique Della Torre, Lúcia Arisaka Paes, Adriana Perez Ferreira-Neto, Letícia Esposito Sewaybricker, Thiago Salum Fontana, Eloisa Helena Rubello Valler Celeri, Gil Guerra-Júnior, Paulo Dalgalarrondo
[This corrects the article DOI: 10.1155/2016/5872423.].
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28571507/the-genetic-basis-of-antiplatelet-and-anticoagulant-therapy-a-pharmacogenetic-review-of-newer-antiplatelets-clopidogrel-prasugrel-and-ticagrelor-and-anticoagulants-dabigatran-rivaroxaban-apixaban-and-edoxaban
#11
REVIEW
Cormac T O'connor, Thomas J Kiernan, Bryan P Yan
The study of pharmacogenomics presents the possibility of individualised optimisation of drug therapy tailored to each patients' unique physiological traits. Both antiplatelet and anticoagulant drugs play a key role in the management of cardiovascular disease. Despite their importance, there is a substantial volume of literature to suggest marked person-to-person variability in their effect. Areas covered: This article reviews the data available for the genetic cause for this inter-patient variability of antiplatelet and anticoagulant drugs...
July 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28431457/precision-medicine-and-pharmacogenetics-what-does-oncology-have-that-addiction-medicine-does-not
#12
Henry R Kranzler, Rachel V Smith, Robert Schnoll, Afaf Moustafa, Emma Greenstreet-Akman
BACKGROUND AND AIMS: Precision, personalized or stratified medicine, which promises to deliver the right treatment to the right patient, is a topic of international interest in both the lay press and the scientific literature. A key aspect of precision medicine is the identification of biomarkers that predict the response to medications (i.e. pharmacogenetics). We examined why, despite the great strides that have been made in biomarker identification in many areas of medicine, only in oncology has there been substantial progress in their clinical implementation...
April 21, 2017: Addiction
https://www.readbyqxmd.com/read/28421156/the-personalization-of-clopidogrel-antiplatelet-therapy-the-role-of-integrative-pharmacogenetics-and-pharmacometabolomics
#13
REVIEW
Arwa M Amin, Lim Sheau Chin, Dzul Azri Mohamed Noor, Muhamad Ali Sk Abdul Kader, Yuen Kah Hay, Baharudin Ibrahim
Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing...
2017: Cardiology Research and Practice
https://www.readbyqxmd.com/read/28351962/pharmacogenetic-associations-of-%C3%AE-1-adrenergic-receptor-polymorphisms-with-cardiovascular-outcomes-in-the-sps3-trial-secondary-prevention-of-small-subcortical-strokes
#14
RANDOMIZED CONTROLLED TRIAL
Oyunbileg Magvanjav, Caitrin W McDonough, Yan Gong, Leslie A McClure, Robert L Talbert, Richard B Horenstein, Alan R Shuldiner, Oscar R Benavente, Braxton D Mitchell, Julie A Johnson
BACKGROUND AND PURPOSE: Functional polymorphisms (Ser49Gly and Arg389Gly) in ADRB1 have been associated with cardiovascular and β-blocker response outcomes. Herein we examined associations of these polymorphisms with major adverse cardiovascular events (MACE), with and without stratification by β-blocker treatment in patients with a history of stroke. METHODS: Nine hundred and twenty-six participants of the SPS3 trial's (Secondary Prevention of Small Subcortical Strokes) genetic substudy with hypertension were included...
May 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28332511/risk-of-acute-myocardial-infarction-after-discontinuation-of-antihypertensive-agents-a-case-control-study
#15
F F Alharbi, P C Souverein, M C de Groot, A H Maitland-van der Zee, A de Boer, O H Klungel
We performed a nested case-control study in a cohort of antihypertensive drug users to assess the association between discontinuation of different antihypertensive agents and the risk of acute myocardial infarction (AMI). Cases and controls were drawn from the Utrecht Cardiovascular Pharmacogenetics database. Patients who were hospitalised for their first AMI were considered cases and controls were not hospitalised for AMI. Antihypertensive users were defined as current users if the index date (date of AMI) fell within the prescribed duration or as discontinuers if this date fell outside the prescribed duration...
August 2017: Journal of Human Hypertension
https://www.readbyqxmd.com/read/28255814/frequency-of-single-nucleotide-platelet-receptor-gene%C3%A2-polymorphism-p2y12-i744t-c-in-coronary-artery-disease-patients-among-tamilian-population
#16
R Priyadharsini, G Umamaheswaran, T A R Raja, A S Arun Kumar, K Subraja, S A Dkhar, S Satheesh, C Adithan, D G Shewade
Several factors contribute to the development of coronary artery disease (CAD). Adenosine diphosphate (ADP) activated P2Y12 receptor also plays a key role in platelet activation and aggregation. It has been found that common variation in the P2Y12 gene was associated with increased platelet aggregation resulting in adverse cardiovascular outcomes. Thus, polymorphisms in the ADP receptor P2Y12 may contribute to the development of CAD. This study aims to determine the frequency distribution of platelet receptor polymorphism P2Y12 (i744T>C) in Tamilian population and to predict its possible role in CAD...
April 2017: Journal of Community Genetics
https://www.readbyqxmd.com/read/28237404/pharmacogenetics-in-cardiovascular-diseases-state-of-the-art-and-implementation-recommendations-of-the-french-national-network-of-pharmacogenetics-rnpgx
#17
REVIEW
Fabien Lamoureux, Thomas Duflot
The use of genomic markers to predict drug response and effectiveness has the potential to improve healthcare by increasing drug efficacy and minimizing adverse effects. Polymorphisms associated with inter-individual variability in drug metabolism, transport, or pharmacodynamics of major cardiovascular drugs have been identified. These include single nucleotide polymorphisms (SNP) affecting clinical outcomes in patients receiving antiplatelet agents, oral anticoagulants and statins. Based on clinical evidence supporting genetic testing in the management of cardiovascular diseases using these drug classes, this short review presents clinical guidance regarding current pharmacogenetics implementation in routine medical practice...
April 2017: Thérapie
https://www.readbyqxmd.com/read/28117133/pharmacogenetics-of-ecstasy-cyp1a2-cyp2c19-and-cyp2b6-polymorphisms-moderate-pharmacokinetics-of-mdma-in-healthy-subjects
#18
Patrick Vizeli, Yasmin Schmid, Katharina Prestin, Henriette E Meyer Zu Schwabedissen, Matthias E Liechti
In vitro studies showed that CYP2C19, CYP2B6, and CYP1A2 contribute to the metabolism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) to 3,4-methylenedioxyamphetamine (MDA). However, the role of genetic polymorphisms in CYP2C19, CYP2B6, and CYP1A2 in the metabolism of MDMA in humans is unknown. The effects of genetic variants in these CYP enzymes on the pharmacokinetics and pharmacodynamics of MDMA were characterized in 139 healthy subjects (69 male, 70 female) in a pooled analysis of eight double-blind, placebo-controlled studies...
January 20, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28117005/pharmacogenomic-challenges-in-cardiovascular-diseases-examples-of-drugs-and-considerations-for-future-integration-in-clinical-practice
#19
Jérôme Chatelin, Maria G Stathopoulou, Alex-Ander Aldasoro Arguinano, Ting Xie, Sophie Visvikis-Siest
Introduction Even if cardiovascular disease (CVD) drugs are supported by high level proofs, the results of CVD treatment present great disparities: there are still patients dying with supposed optimal treatment, patients facing adverse events and CVD remain the primary cause of death in the world. Pharmacogenomics is the basis of personalisation of the treatment able to allow higher medication success rates. In this review, we will present detailed examples of CVD drugs to highlight the complexity of this challenging field and we will discuss novel concepts that should be considered for a fastest integration of pharmacogenomics in clinical practice of CVD...
January 23, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28057368/genomic-translational-research-paving-the-way-to-individualized-cardiac-functional-analyses-and-personalized-cardiology
#20
REVIEW
Ares Pasipoularides
For most of Medicine's past, the best that physicians could do to cope with disease prevention and treatment was based on the expected response of an average patient. Currently, however, a more personalized/precise approach to cardiology and medicine in general is becoming possible, as the cost of sequencing a human genome has declined substantially. As a result, we are witnessing an era of precipitous advances in biomedicine and bourgeoning understanding of the genetic basis of cardiovascular and other diseases, reminiscent of the resurgence of innovations in physico-mathematical sciences and biology-anatomy-cardiology in the Renaissance, a parallel time of radical change and reformation of medical knowledge, education and practice...
March 1, 2017: International Journal of Cardiology
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