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Pharmacogenomics review

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https://www.readbyqxmd.com/read/29032303/current-strategies-to-streamline-pharmacotherapy-for-older-adults
#1
REVIEW
Jan-F Schlender, Valvanera Vozmediano, Adam G Golden, Monica Rodriguez, Tanay S Samant, Chakradhar V Lagishetty, Thomas Eissing, Stephan Schmidt
Although the term "personalized medicine" has been associated in many cases with pharmacogenomics, its definition embraces the use of specific biomarkers and covariates to help in the selection of medical treatments and procedures which are best for each patient. While several efforts have been performed for the tailored selection of therapies and dosing regimens in the general population, developing personalized medicine initiatives for elderly patients remains understudied. The personalized drug therapy for older patients requires the consideration of anatomical, physiological and functional alterations in a multimorbid setting requiring multiple medications...
October 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29030886/genetics-of-acute-rejection-after-kidney-transplantation
#2
REVIEW
Casey R Dorr, William S Oetting, Pamala A Jacobson, Ajay K Israni
Treatment of acute rejection (AR) following kidney transplantation has improved in recent years, but there are still limitations to successful outcomes. This review article covers literature in regards to recipient and donor genetics of AR kidney and secondarily of liver allografts. Many candidate gene and some genome wide association studies (GWAS) have been conducted for AR in kidney transplantation. Genetic associations with AR in kidney and liver are mostly weak and in most cases the associations have not been reproducible...
October 14, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29022838/pharmacogenomics-of-triazole-antifungal-agents-implications-for-safety-tolerability-and-efficacy
#3
Jarrett R Amsden, Paul O Gubbins
Introduction Triazole antifungal agents are prescribed to treat invasive fungal infections in neutropenic and non-neutropenic patients. These antifungal agents are substrates and inhibitors of cytochrome P450 (CYP). Genetic polymorphisms in CYP2C9, CYP2C19 and CYP3A5 can lead to large population-specific variations in drug efficacy and safety, optimal dosing, or contribute to drug interactions associated with this class. Areas covered This manuscript reviews the pharmacogenomics (i.e. the influence of genetics on drug disposition) of triazole antifungal agents related to their CYP-mediated metabolism and summarizes their implications on triazole efficacy, safety, and tolerability...
October 12, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29021832/pharmacogenomics-in-the-treatment-of-mood-disorders-strategies-and-opportunities-for-personalized-psychiatry
#4
REVIEW
Azmeraw T Amare, Klaus Oliver Schubert, Bernhard T Baune
Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/28990639/pharmacogenomics-and-psychiatric-clinical-care
#5
Russell J Amato, Joseph Boland, Nicole Myer, Lauren Few, Daniel Dowd
Approximately one in five individuals in the United States experiences mental health issues in any given year, and these disorders are consistently among the leading causes of years lived with disability. Unfortunately, many mental illnesses are lifelong conditions that require medication and therapy to improve quality of life, yet clinical trial data show that many patients fail to achieve remission or require several pharmacological interventions prior to remission. These results indicate a need to address the variability among patients in their response to medication, in addition to developing treatment plans tailored to the individual...
October 6, 2017: Journal of Psychosocial Nursing and Mental Health Services
https://www.readbyqxmd.com/read/28986727/dpp-4-inhibitors-and-heart-failure-a-potential-role-for-pharmacogenomics
#6
REVIEW
Chayakrit Krittanawong, Andrew Xanthopoulos, Takeshi Kitai, Natalia Branis, HongJu Zhang, Marrick Kukin
There remains an ongoing controversy regarding the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of developing heart failure (HF). In addition, none of the animal studies suggested a mechanism for the DPP-4 inhibitors and HF risk. To date, advances in pharmacogenomics have enabled the identification of genetic variants in DPP-4 gene. Studies have shown that genetic polymorphisms in the gene encoding DPP-4 may be associated with potential pathways involved in HF risk. This review discusses the contradictory findings of DPP-4 inhibitors and HF and a potential role for pharmacogenomics...
October 6, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28975860/advancing-psychiatric-pharmacogenomics-using-drug-development-paradigms
#7
Ryan M Smith
Drugs used to treat psychiatric disorders, even when taken as directed, fail to provide adequate relief for a sizeable proportion of patients. Despite our advancements in understanding human genetics and development of high-throughput tools to probe variation, pharmacogenomics has yielded marginal ability to predict drug response for psychiatric disorders. Here, I review the current pharmacogenomics paradigm, identifying opportunities to incorporate drug development strategies designed to increase the probability of delivering a successful molecule to the clinic...
October 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28963061/simplifying-the-use-of-pharmacogenomics-in-clinical-practice-building-the-genomic-prescribing-system
#8
Keith Danahey, Brittany A Borden, Brian Furner, Patrick Yukman, Sheena Hussain, Donald Saner, Samuel L Volchenboum, Mark J Ratain, Peter H O'Donnell
BACKGROUND: A barrier to the use of genomic information during prescribing is the limited number of software solutions that combine a user-friendly interface with complex medical data. We built and designed an online, secure, electronic custom interface termed the Genomic Prescribing System (GPS). METHODS: Actionable pharmacogenomic (PGx) information was reviewed, collected, and stored in the back-end of GPS to enable creation of customized drug- and variant-specific clinical decision support (CDS) summaries...
September 26, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/28949250/the-challenges-of-implementing-pharmacogenomic-testing-in-the-clinic
#9
Ann M Moyer, Pedro J Caraballo
Pharmacogenomic testing has the potential to greatly benefit patients by enabling personalization of medication management, ensuring better efficacy and decreasing the risk of side effects. However, to fully realize the potential of pharmacogenomic testing, there are several important issues that must be addressed. Areas covered: In this expert review we discuss current challenges impacting the implementation of pharmacogenomic testing in the clinical practice. We emphasize issues related to testing methods, reporting of the results, test selection, clinical interpretation of the results, cost-effectiveness, and the long-term use of pharmacogenomic results in clinical practice...
October 3, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28945944/whole-transcriptome-profiling-an-rna-seq-primer-and-implications-for-pharmacogenomics-research
#10
Ana Caroline Costa Sá, Wolfgang Sadee, Julie A Johnson
Pharmacogenomics has revealed compelling genetic signals associated with variability in drug response. Gene expression studies represent an additional approach to identify candidate genes accounting for drug response variability. This review focuses on insights that might be gained through analysis of the transcriptome to reveal the influence of gene expression on variable drug response. We provide a basic overview of RNA-Sequencing (RNA-Seq) and its applications, and outline advances in pharmacogenomics achievable with RNA-Seq data...
September 25, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28944433/pharmacogenetics-of-lipid-lowering-agents-an-update-review-on-genotype-dependent-effects-of-hdl-targetingand-statin-therapies
#11
REVIEW
Nathan Messas, Marie-Pierre Dubé, Jean-Claude Tardif
PURPOSE OF REVIEW: High-density lipoproteins (HDL) are involved in reverse cholesterol transport. Results from randomized trials of HDL-targeting therapies, including cholesteryl ester transfer protein (CETP) inhibitors, have shown a lack of benefit in unsegmented populations. These observations could be explained by inter-individual variability of clinical responses to such agents depending on the patients' genotypes. In parallel, although lowering of LDL cholesterol (LDL-c) with statin therapy reduces the risk of vascular events in a wide range of individuals, inter-individual variability exists with regard to LDL-c-lowering response as well as efficacy in reducing major cardiovascular events...
September 25, 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28933291/pharmacotranscriptomic-biomarkers-in-glucocorticoid-treatment-of-pediatric-inflammatory-bowel-disease
#12
Marianna Lucafò, Biljana Stankovic, Nikola Kotur, Alessia Di Silvestre, Stefano Martelossi, Alessandro Ventura, Branka Zukic, Sonya Pavlovic, Giuliana Decorti
Pharmacotranscriptomics aims to reach more accurate drug dosing based on interindividual transcriptome variations. Here, we provide an overview of RNA biomarkers that could predict the response to glucocorticoids (GCs), considered the standard for treatment of inflammatory bowel diseases (IBD), both in adult and pediatric patients. Although new biological agents are very effective in the IBD treatment, GCs are still widely used for induction of remission in IBD patients with moderate to severe disease. It is important to identify patients that are poor responders to GCs therapy, because suboptimal response is frequent and associated with various side effects...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28921647/pharmacogenomics-implementation-at-the-national-institutes-of-health-clinical-center
#13
Tristan M Sissung, Jon W McKeeby, Jharana Patel, Juan J Lertora, Parag Kumar, Willy A Flegel, Sharon D Adams, Ellen J Eckes, Frank Mickey, Teri M Plona, Stephanie D Mellot, Ryan N Baugher, Xiaolin Wu, Daniel R Soppet, Mary E Barcus, Vivekananda Datta, Kristen M Pike, Gary DiPatrizio, William D Figg, Barry R Goldspiel
The National Institutes of Health Clinical Center (NIH CC) is the largest hospital in the United States devoted entirely to clinical research, with a highly diverse spectrum of patients. Patient safety and clinical quality are major goals of the hospital, and therapy is often complicated by multiple cotherapies and comorbidities. To this end, we implemented a pharmacogenomics program in 2 phases. In the first phase, we implemented genotyping for HLA-A and HLA-B gene variations with clinical decision support (CDS) for abacavir, carbamazepine, and allopurinol...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921458/pharmacogenetics-and-pharmacogenomics-in-moderate-to-severe-psoriasis
#14
REVIEW
María C Ovejero-Benito, Ester Muñoz-Aceituno, Alejandra Reolid, Miriam Saiz-Rodríguez, Francisco Abad-Santos, Esteban Daudén
Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis...
September 18, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28899477/-research-advances-in-pharmacogenomics-of-mercaptopurine
#15
Xiao-Xiao Chen, Shu-Hong Shen
Mercaptopurine is a common chemotherapeutic drug and immunosuppressive agent and plays an important role in the treatment of acute lymphoblastic leukemia and inflammatory bowel disease. It may cause severe adverse effects such as myelosuppression, which may result in the interruption of treatment or complications including infection or even threaten patients' lives. However, the adverse effects of mercaptopurine show significant racial and individual differences, which reveal the important role of genetic diversity...
September 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28891449/role-of-pharmacogenomics-in-antiepileptic-drug-therapy-current-status-and-future-perspectives
#16
Antonio Gambardella, Angelo Labate, Laura Mumoli, Iscia Lopes-Cendes, Fernando Cendes
BACKGROUND: Growing evidence indicates that pharmacogenomics will positively impact treatment for patients with epilepsy in the near future, leading to the implementation of a precision-based use of antiepileptic drug (AED) therapy, thereby providing a cornerstone for precision medicine. OBJECTIVE: In this review, we briefly summarize the studies of pharmacogenomics in epilepsy, recent advances, and how it may progress in the future. METHODS: We subdivided the review into two main sections: genetic variants that may modulate response to AEDs through pharmacokinetics or pharmacodynamics mechanisms; and gene variants that may affect tolerability and safety of AEDs...
September 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28887371/germline-genetic-variants-with-implications-for-disease-risk-and-therapeutic-outcomes
#17
Amy L Pasternak, Kristen M Ward, Jasmine A Luzum, Vicki L Ellingrod, Daniel L Hertz
Genetic testing has multiple clinical applications including disease risk assessment, diagnosis and pharmacogenomics. Pharmacogenomics can be utilized to predict whether a pharmacologic therapy will be effective or to identify patients at risk for treatment-related toxicity. Although genetic tests are typically ordered for a distinct clinical purpose, the genetic variants that are found may have additional implications for either disease or pharmacology. This review will address multiple examples of germline genetic variants that are informative for both disease and pharmacogenomics...
September 8, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28878340/the-pharmacogenomics-of-valproic-acid
#18
REVIEW
Miao-Miao Zhu, Hui-Lan Li, Li-Hong Shi, Xiao-Ping Chen, Jia Luo, Zan-Ling Zhang
Valproic acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. Adverse effects of valproic acid are rare, but hepatotoxicity is severe in particular in those younger than 2 years old and polytherapy. During valproic acid treatment, it is difficult for prescribers to predict its individual response. Recent advances in the field of pharmacogenomics have indicated variants of candidate genes that affect valproic acid efficacy and safety. In this review, a large number of candidate genes that influence valproic acid pharmacokinetics and pharmacodynamics are discussed, including metabolic enzymes, drug transporters, neurotransmitters and drug targets...
September 7, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28868359/immune-mediator-pharmacogenomics-tcl1a-snps-and-estrogen-dependent-regulation-of-inflammation
#19
Ming-Fen Ho, Richard M Weinshilboum
This review describes the important functional implications of TCL1A single nucleotide polymorphisms (SNPs) discovered during pharmacogenomic studies of aromatase inhibitor-induced musculoskeletal adverse events that were subsequently shown to influence the expression of cytokines, chemokines, toll-like receptors (TLR), and NF-κB in a SNP and estrogen-dependent fashion. Functional genomic studies of these SNPs led to the discovery of novel mechanisms that may contribute to disease pathophysiology and which may also increase our understanding of pharmacogenomic aspects of regulation of the expression of inflammatory mediators...
August 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28860839/updating-the-landscape-of-direct-to-consumer-pharmacogenomic-testing
#20
REVIEW
Kelly K Filipski, John D Murphy, Kathy J Helzlsouer
Pharmacogenomics has identified important drug-gene interactions that affect the safety and efficacy of medications. Direct-to-consumer genetic testing, when first introduced, included some pharmacogenomic-related genes. The current landscape of pharmacogenomic direct-to-consumer testing is reviewed. Prior published reviews of the literature were updated through February 2017 and a scan of the current availability of direct-to-consumer genomic testing by companies was conducted. Results of the review demonstrate a shift toward physician-approved ordering...
2017: Pharmacogenomics and Personalized Medicine
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