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Pharmacogenomics and Personalized Medicine

Joseph P Kitzmiller, Eduard B Mikulik, Anees M Dauki, Chandrama Murkherjee, Jasmine A Luzum
Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy...
2016: Pharmacogenomics and Personalized Medicine
Dmitry Alekseevich Sychev, Mikhail Sergeevich Zastrozhin, Valery Valerieevich Smirnov, Elena Anatolievna Grishina, Ludmila Mikhailovna Savchenko, Evgeny Alekseevich Bryun
BACKGROUND: Today, it is proved that isoenzymes CYP2D6 and CYP3A4 are involved in metabolism of haloperidol. In our previous investigation, we found a medium correlation between the efficacy and safety of haloperidol and the activity of CYP3A4 in patients with alcohol abuse. OBJECTIVE: The aim of this study was to evaluate the correlation between the activity of CYP2D6 and the efficacy and safety of haloperidol in patients with diagnosed alcohol abuse. METHODS: The study involved 70 men (average age: 40...
2016: Pharmacogenomics and Personalized Medicine
Anton Jm Loonen, Robbert-Jan Verkes
No abstract text is available yet for this article.
2016: Pharmacogenomics and Personalized Medicine
Eve S Fields, Raymond A Lorenz, Joel G Winner
This report describes two cases in which pharmacogenomic testing was utilized to guide medication selection for difficult to treat patients. The first patient is a 29-year old male with bipolar disorder who had severe akathisia due to his long acting injectable antipsychotic. The second patient is a 59-year old female with major depressive disorder who was not responding to her medication. In both cases, a proprietary combinatorial pharmacogenomic test was used to inform medication changes and improve patient outcomes...
2016: Pharmacogenomics and Personalized Medicine
Jai N Patel
Cancer pharmacogenomics is an evolving landscape and has the potential to significantly impact cancer care and precision medicine. Harnessing and understanding the genetic code of both the patient (germline) and the tumor (somatic) provides the opportunity for personalized dose and therapy selection for cancer patients. While germline DNA is useful in understanding the pharmacokinetic and pharmacodynamic disposition of a drug, somatic DNA is particularly useful in identifying drug targets and predicting drug response...
2016: Pharmacogenomics and Personalized Medicine
Dmitrij Alekseevitch Sychev, Grigorij Nikolaevich Shuev, Jana Valer'evna Chertovskih, Nadezhda Romanovna Maksimova, Andrej Vladimirovich Grachev, Ol'ga Aleksandrovna Syrkova
INTRODUCTION: Statins are the most commonly prescribed medicines for treatment of hypercholesterolemia. At the same time, up to 25% of patients cannot tolerate or have to discontinue the statin therapy due to statin-induced myopathy. In a majority of cases, statin-induced myopathy is attributed to SLCO1B1 gene polymorphism. The strongest association between statin-induced myopathy and SLCO1B1 gene polymorphism was described for simvastatin. Our research was focused on the frequency of SLCO1B1*5 genetic variant in the Russian population and in the native population of Sakha (Yakutia)...
2016: Pharmacogenomics and Personalized Medicine
Sonam Tulsyan, Rama Devi Mittal, Balraj Mittal
The ABCB1 gene encodes a permeability glycoprotein, which is one of the most extensively studied human adenosine-triphosphate (ATP)-dependent efflux transporters. Permeability glycoprotein is expressed in the apical membranes of tissues such as intestine, liver, blood-brain barrier, kidney, placenta, and testis and contributes to intracellular drug disposition. It is also highly expressed in tumor cells conferring drug resistance, which is one of the major problems in the efficacy of cancer chemotherapy treatment...
2016: Pharmacogenomics and Personalized Medicine
Joseph Finkelstein, Carol Friedman, George Hripcsak, Manuel Cabrera
Pharmacogenomic (PGx) testing has been increasingly used to optimize drug regimens; however, its potential in older adults with polypharmacy has not been systematically studied. In this hypothesis-generating study, we employed a case series design to explore potential utility of PGx testing in older adults with polypharmacy and to highlight barriers in implementing this methodology in routine clinical practice. Three patients with concurrent chronic heart and lung disease aged 74, 78, and 83 years and whose medication regimen comprised 26, 17, and 18 drugs, correspondingly, served as cases for this study...
2016: Pharmacogenomics and Personalized Medicine
Adem Yesuf Dawed, Kaixin Zhou, Ewan Robert Pearson
Type 2 diabetes is one of the leading causes of morbidity and mortality, consuming a significant proportion of public health spending. Oral hypoglycemic agents (OHAs) are the frontline treatment approaches after lifestyle changes. However, huge interindividual variation in response to OHAs results in unnecessary treatment failure. In addition to nongenetic factors, genetic factors are thought to contribute to much of such variability, highlighting the importance of the potential of pharmacogenetics to improve therapeutic outcome...
2016: Pharmacogenomics and Personalized Medicine
Meagan B Myers
Breast cancer is a multifaceted disease exhibiting both intertumoral and intratumoral heterogeneity as well as variable disease course. Over 2 decades of research has advanced the understanding of the molecular substructure of breast cancer, directing the development of new therapeutic strategies against these actionable targets. In vitro diagnostics, and specifically companion diagnostics, have been integral in the successful development and implementation of these targeted therapies, such as those directed against the human epidermal growth factor receptor 2...
2016: Pharmacogenomics and Personalized Medicine
Juan-Sebastian Saldivar, David Taylor, Elaine A Sugarman, Ali Cullors, Jorge A Garces, Kahuku Oades, Joel Centeno
The health care costs associated with prescription drugs are enormous, particularly in patients with polypharmacy (taking more than five prescription medications), and they continue to grow annually. The evolution of pharmacogenetics has provided clinicians with a valuable tool that allows for a smarter, more fine-tuned approach to treating patients for a number of clinical conditions. Applying a pharmacogenetics approach to the medical management of patients can provide a significant improvement to their care, result in cost savings by reducing the use of ineffective drugs, and decrease overall health care utilization...
2016: Pharmacogenomics and Personalized Medicine
Steffen Heeg
Immortalization is an important step toward the malignant transformation of human cells and is critically dependent upon telomere maintenance. There are two known mechanisms to maintain human telomeres. The process of telomere maintenance is either mediated through activation of the enzyme telomerase or through an alternative mechanism of telomere lengthening called ALT. While 85% of all human tumors show reactivation of telomerase, the remaining 15% are able to maintain telomeres via ALT. The therapeutic potential of telomerase inhibitors is currently investigated in a variety of human cancers...
2015: Pharmacogenomics and Personalized Medicine
Pansachee Damronglerd, Chonlaphat Sukasem, Wilawan Thipmontree, Apichaya Puangpetch, Sasisopin Kiertiburanakul
OBJECTIVE: We aimed at comparing clinical/immunological outcomes in human immunodeficiency virus (HIV)-infected patients who were treated with CYP2B6-guided and conventional efavirenz (EFV) therapy. METHODS: This study was a 24-week prospective randomized controlled trial. Eligible patients were HIV-infected adults yet to start antiretroviral therapy. Twenty-four HIV-infected patients were recruited and randomly assigned to genotype CYP2B6 polymorphism before ART initial dose...
2015: Pharmacogenomics and Personalized Medicine
Hazem El-Osta, Rodney Shackelford
The fusion of echinoderm microtubule-associated protein-like 4 with the anaplastic lymphoma kinase (EML4-ALK) is found in 3%-7% of non-small-cell lung cancer (NSCLC) cases and confers sensitivity to crizotinib, the first United States Food and Drug Administration (FDA)-approved ALK inhibitor drug. Although crizotinib has an excellent initial therapeutic effect, acquired resistance to this drug invariably develops within the first year of treatment. Resistance may involve secondary gatekeeper mutations within the ALK gene interfering with crizotinib-ALK interactions, or compensatory activation of aberrant bypass signaling pathways...
2015: Pharmacogenomics and Personalized Medicine
Asalaysa Bushyakanist, Apichaya Puangpetch, Chonlaphat Sukasem, Sasisopin Kiertiburanakul
OBJECTIVES: The objectives of this study were to describe the use of pharmacogenetics in clinical practice for the treatment of individuals with human immunodeficiency virus (HIV) infection and to determine the treatment outcomes of HIV-infected patients in whom pharmacogenetic testing was performed. METHODS: This study involves a retrospective collection of medical records of HIV-infected patients who attended Ramathibodi Hospital during January 2011 to November 2014 and in whom pharmacogenetic testing was performed...
2015: Pharmacogenomics and Personalized Medicine
Jiska M Balk, Guido Rmm Haenen, Özgür M Koc, Ron Peters, Aalt Bast, Wim Jf van der Vijgh, Ger H Koek
BACKGROUND: The combination of ribavirin (RBV) and pegylated interferon (PEG-IFN) is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens...
2015: Pharmacogenomics and Personalized Medicine
Kristin Bixel, John L Hays
Alterations in the homologous repair pathway are thought to occur in 30%-50% of epithelial ovarian cancers. Cells deficient in homologous recombination rely on alternative pathways for DNA repair in order to survive, thereby providing a potential target for therapy. Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, capitalizes on this concept and is the first drug in its class approved for patients with ovarian cancer. This review article will provide an overview of the BRCA genes and homologous recombination, the role of PARP in DNA repair and the biological rationale for the use of PARP inhibitors as cancer therapy, and ultimately will focus on the use of olaparib in the management of ovarian cancer...
2015: Pharmacogenomics and Personalized Medicine
Fatiha H Shabaruddin, Nigel D Fleeman, Katherine Payne
Personalized medicine, with the aim of safely, effectively, and cost-effectively targeting treatment to a prespecified patient population, has always been a long-time goal within health care. It is often argued that personalizing treatment will inevitably improve clinical outcomes for patients and help achieve more effective use of health care resources. Demand is increasing for demonstrable evidence of clinical and cost-effectiveness to support the use of personalized medicine in health care. This paper begins with an overview of the existing challenges in conducting economic evaluations of genetics- and genomics-targeted technologies, as an example of personalized medicine...
2015: Pharmacogenomics and Personalized Medicine
D A Sychev, N P Denisenko, Z M Sizova, A V Grachev, K A Velikolug
INTRODUCTION: Proton pump inhibitors, which are widely used as acid-inhibitory agents for the treatment of peptic ulcers, are mainly metabolized by 2C19 isoenzyme of cytochrome P450 (CYP2C19). CYP2C19 has genetic polymorphisms, associated with extensive, poor, intermediate or ultra-rapid metabolism of proton pump inhibitors. Genetic polymorphisms of CYP2C19 could be of clinical concern in the treatment of peptic ulcers with proton pump inhibitors. AIM: To investigate the frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcers...
2015: Pharmacogenomics and Personalized Medicine
Amit Agarwal, Dan Ressler, Glenn Snyder
Companion diagnostics are an indispensable part of personalized medicine and will likely continue to rapidly increase in number and application to disease areas. The first companion diagnostics were launched in the 1980s and in the face of significant initial skepticism from drug developers as to whether segmenting a drug's market through a diagnostic was advisable. The commercial success of drugs such as Herceptin® (trastuzumab) and Gleevec® (imatinib), which both require testing with companion diagnostics before they can be prescribed, has moved the entire companion diagnostic field forward...
2015: Pharmacogenomics and Personalized Medicine
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