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Genes Nov 2020Realizing the promise of precision medicine in psychiatry is a laudable and beneficial endeavor, since it should markedly reduce morbidity and mortality and, in effect,... (Review)
Review
Realizing the promise of precision medicine in psychiatry is a laudable and beneficial endeavor, since it should markedly reduce morbidity and mortality and, in effect, alleviate the economic and social burden of psychiatric disorders. This review aims to summarize important issues on pharmacogenomics in psychiatry that have laid the foundation towards personalized pharmacotherapy and, in a broader sense, precision medicine. We present major pharmacogenomic biomarkers and their applications in a variety of psychiatric disorders, such as depression, attention-deficit/hyperactivity disorder (ADHD), narcolepsy, schizophrenia, and bipolar disorder. In addition, we extend the scope into epilepsy, since antiepileptic drugs are widely used to treat psychiatric disorders, although epilepsy is conventionally considered to be a neurological disorder.
Topics: Anticonvulsants; Biomarkers; Epilepsy; Humans; Mental Disorders; Pharmacogenetics; Precision Medicine; Psychiatry
PubMed: 33266292
DOI: 10.3390/genes11121445 -
Pharmacotherapy Jul 2023Solid organ transplant recipients are reliant on immunosuppressive drugs, which have a narrow therapeutic index, and are concurrently vulnerable to adverse drug events... (Review)
Review
Solid organ transplant recipients are reliant on immunosuppressive drugs, which have a narrow therapeutic index, and are concurrently vulnerable to adverse drug events due to comorbidity burden and the complexity of their medication regimens. Urgent management of post-transplant complications often falls to the generalist clinician or critical care specialist. The purpose of this narrative review is to discuss innovations and bedside applications of pharmacogenomics and therapeutic drug monitoring applied to immunosuppression and agents frequently encountered in transplant recipients. Medication formulations will be given specific attention, as interchange is frequently required in the acute care setting. Bioassays quantifying immune system activity will be described with practical applications. A structured approach to addressing drug-drug, drug-gene, and drug-drug-gene interactions will be modeled using a case-based approach synthesizing pharmacogenomics, therapeutic drug monitoring, pharmacokinetics, and pharmacodynamic principles.
Topics: Humans; Pharmacogenetics; Transplant Recipients; Immunosuppressive Agents; Immunosuppression Therapy; Organ Transplantation; Tacrolimus
PubMed: 36999337
DOI: 10.1002/phar.2798 -
Clinical Pharmacology and Therapeutics Nov 2019
Topics: Databases, Genetic; Decision Support Systems, Clinical; Electronic Health Records; Humans; Leadership; Pharmacogenetics; Pharmacogenomic Variants; Precision Medicine
PubMed: 31498426
DOI: 10.1002/cpt.1600 -
Pharmacogenomics Apr 2022Global migration trends are accelerating population admixture. Increasing population diversity met with minority health disparities necessitates thoughtful training of... (Review)
Review
Global migration trends are accelerating population admixture. Increasing population diversity met with minority health disparities necessitates thoughtful training of health professional students. Health professional accreditation standards emphasize pharmacogenomics and clinical cultural competency (CCC); however, published studies focus on students' knowledge in pharmacogenomics alone. This report reviews considerations for integrating CCC into required pharmacogenomic education in pharmacy and other health disciplines. By coupling both topics during didactic training and active learning exercises repeated throughout the existing curriculum, students can become adept at these individualized patient care skills and retain their knowledge into their careers. Moving beyond race as a proxy for healthcare decision-making, the CCC of clinicians coupled with patients' genetic test results could empower clinicians to address health disparities and facilitate discussions about the role of race in clinical practice. Ultimately, an integrated approach of teaching pharmacogenomics and CCC could dismantle race-norming or race-based clinical practices.
Topics: Clinical Competence; Cultural Competency; Curriculum; Education, Pharmacy; Humans; Pharmacogenetics
PubMed: 35311348
DOI: 10.2217/pgs-2022-0009 -
Pharmacogenomics Aug 2019The Nigerian population exhibits huge ethnic and genetic diversity, typical of African populations, which can be harnessed for improved drug-response and disease... (Review)
Review
The Nigerian population exhibits huge ethnic and genetic diversity, typical of African populations, which can be harnessed for improved drug-response and disease management. Existing data on genes relevant to drug response, so far generated for the population, indeed confirm the prevalence of some clinically significant pharmacogenes. These reports detail prevailing genetic alleles and metabolic phenotypes of vital drug metabolizing monooxygenases, transferases and drug transporters. While the utilization of existing pharmacogenomic data for healthcare delivery remains unpopular, several past and on-going studies suggest that a future shift toward genotype-stratified dosing of drugs and disease management in the population is imminent. This review discusses the present state of pharmacogenomics in Nigeria and the potential benefits of sustained research in this field for the population.
Topics: Alleles; Animals; Ethnicity; Genetic Variation; Genotype; Humans; Nigeria; Pharmacogenetics; Phenotype
PubMed: 31453771
DOI: 10.2217/pgs-2019-0046 -
Human Molecular Genetics May 2018The field of pharmacogenomics is an area of great potential for near-term human health impacts from the big genomic data revolution. Pharmacogenomics research momentum... (Review)
Review
The field of pharmacogenomics is an area of great potential for near-term human health impacts from the big genomic data revolution. Pharmacogenomics research momentum is building with numerous hypotheses currently being investigated through the integration of molecular profiles of different cell lines and large genomic data sets containing information on cellular and human responses to therapies. Additionally, the results of previous pharmacogenetic research efforts have been formulated into clinical guidelines that are beginning to impact how healthcare is conducted on the level of the individual patient. This trend will only continue with the recent release of new datasets containing linked genotype and electronic medical record data. This review discusses key resources available for pharmacogenomics and pharmacogenetics research and highlights recent work within the field.
Topics: Big Data; Genomics; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 29635477
DOI: 10.1093/hmg/ddy116 -
Biomedicine & Pharmacotherapy =... Jun 2022Mendelian randomization (MR) is an epidemiological method that uses genetic variants to proxy an exposure predicting its causal association with an outcome. It occupies... (Review)
Review
Mendelian randomization (MR) is an epidemiological method that uses genetic variants to proxy an exposure predicting its causal association with an outcome. It occupies a valuable niche between observational studies and randomized trials. MR applications expanded lately, facilitated by the availability of big data, to include disease risk causation prediction, supporting evidence of prior observational data, identifying new drug targets, and drug repurposing. Concurrently, the last decade witnessed the growth of pharmacogenomics (PGx) research as a cornerstone in precision medicine. PGx research, conducted at discovery and implementation levels, resulted in validated PGx biomarkers and tests. Despite many clinically relevant PGx associations that could be translated into clinical applications, worldwide implementation is lagging far behind. The current review examines the intersection zones between MR and PGx research. MR can provide supporting evidence that allows generalizing PGx findings supporting its implementation. Interchangeability, PGx research can fuel MR studies with libraries of genetic variants of validated biological relevance. Furthermore, PGx and MR exhibit a synergistic relationship in drug discovery that can accelerate identifying new targets and repurposing old drugs. Interdisciplinary research applied by PGx researchers, epidemiologists with MR experience, and data scientists' collaborations can unlock unforeseen opportunities in accelerating precision medicine acquisition.
Topics: Drug Discovery; Mendelian Randomization Analysis; Pharmacogenetics; Precision Medicine
PubMed: 35429744
DOI: 10.1016/j.biopha.2022.112952 -
British Journal of Clinical Pharmacology Sep 2023Pharmacogenomic testing has the potential to target medicines more effectively towards those who will benefit and avoid use in individuals at risk of harm. Health... (Review)
Review
AIMS
Pharmacogenomic testing has the potential to target medicines more effectively towards those who will benefit and avoid use in individuals at risk of harm. Health economies are actively considering how pharmacogenomic tests can be integrated into health care systems to improve use of medicines. However, one of the barriers to effective implementation is evaluation of the evidence including clinical usefulness, cost-effectiveness, and operational requirements. We sought to develop a framework that could aid the implementation of pharmacogenomic testing. We take the view from the National Health Service (NHS) in England.
METHODS
We used a literature review using EMBASE and Medline databases to identify prospective studies of pharmacogenomic testing, focusing on clinical outcomes and implementation of pharmacogenomics. Using this search, we identified key themes relating to the implementation of pharmacogenomic tests. We used a clinical advisory group with expertise in pharmacology, pharmacogenomics, formulary evaluation, and policy implementation to review data from our literature review and the interpretation of these data. With the clinical advisory group, we prioritized themes and developed a framework to evaluate proposals to implement pharmacogenomics tests.
RESULTS
Themes that emerged from review of the literature and subsequent discussion were distilled into a 10-point checklist that is proposed as a tool to aid evidence-based implementation of pharmacogenomic testing into routine clinical care within the NHS.
CONCLUSION
Our 10-point checklist outlines a standardized approach that could be used to evaluate proposals to implement pharmacogenomic tests. We propose a national approach, taking the view of the NHS in England. Using this approach could centralize commissioning of appropriate pharmacogenomic tests, reduce inequity and duplication using regional approaches, and provide a robust and evidence-based framework for adoption. Such an approach could also be applied to other health systems.
Topics: Humans; Pharmacogenetics; State Medicine; Pharmacogenomic Testing; Prospective Studies; England
PubMed: 37313748
DOI: 10.1111/bcp.15820 -
Pharmacogenomics Feb 2021Pharmacogenetics represents a major driver of precision medicine, promising individualized drug selection and dosing. Traditionally, pharmacogenetic profiling has been... (Review)
Review
Pharmacogenetics represents a major driver of precision medicine, promising individualized drug selection and dosing. Traditionally, pharmacogenetic profiling has been performed using targeted genotyping that focuses on common/known variants. Recently, whole-genome sequencing (WGS) is emerging as a more comprehensive short-read next-generation sequencing approach, enabling both gene diagnostics and pharmacogenetic profiling, including rare/novel variants, in a single assay. Using the example of the pharmacogene , we demonstrate the potential of WGS-based pharmacogenetic profiling as well as emphasize the limitations of short-read next-generation sequencing. In the near future, we envision a shift toward long-read sequencing as the predominant method for gene diagnostics and pharmacogenetic profiling, providing unprecedented data quality and improving patient care.
Topics: Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Whole Genome Sequencing
PubMed: 33517770
DOI: 10.2217/pgs-2020-0155 -
Pharmacotherapy Sep 2017Increased use of pharmacogenomic (PGx) testing in the clinical setting has revealed a number of challenges to providing this service. PGx is an important component of... (Review)
Review
Increased use of pharmacogenomic (PGx) testing in the clinical setting has revealed a number of challenges to providing this service. PGx is an important component of precision medicine that brings together the fields of genetics and clinical pharmacology. A model that incorporates a multidisciplinary approach to implementation and information delivery may be the most beneficial to patients and providers. In this review, translational considerations in the provision of PGx testing and counseling services are described. Specifically, we report on the selection of PGx tests, the provision of patient education and counseling, and examples of PGx service delivery models that incorporate counseling by pharmacists and genetic counselors. Examples of ancillary risks associated with PGx testing, testing of children, and familial implications of testing are reviewed. Through multispecialty partnerships, including genetic counselors and pharmacists, implementation obstacles to PGx testing can be overcome to provide quality precision medicine to patients.
Topics: Genetic Counseling; Genetic Testing; Humans; Intersectoral Collaboration; Patient Education as Topic; Pharmacogenetics
PubMed: 28672074
DOI: 10.1002/phar.1980