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Gene Nov 2019Individual specific variable drug response against similar drugs raises a significant challenge for the effective and safe treatment of many human diseases.... (Review)
Review
Individual specific variable drug response against similar drugs raises a significant challenge for the effective and safe treatment of many human diseases. Pharmacogenomics is the branch which try to deal with these challenge by relating drug response to patient specific genome in order to better customize patient treatments. Pharmacogenomics based research focus on the whole genome, but since last few years after realizing the importance, it mainly centralized towards genes of pharmacological importance called pharmacogenes, and try to explore association between their variants and variable drug response in world's different population. This research was initiated with the resulted data from human genome based research projects and later on assisted by exome sequencing projects. Simultaneously, it was boost-up with the participation of various pharmacogenomics groups lead by PGRN. By realizing the significance of pharmacogenes, and their variant related information, in health science, scientific communities are already started to look for genes of pharmacogenomics importance with different aspect. This article aims to provide an inclusive insight on current state of knowledge of pharmacogenes, recent trends and progress in the understanding of the pharmacogenes and the implications for personalized medicine.
Topics: Genome, Human; Humans; Pharmacogenetics; Precision Medicine
PubMed: 31425740
DOI: 10.1016/j.gene.2019.144050 -
The Journal of Neuroscience Nursing :... Feb 2022INTRODUCTION: Enteral nimodipine provides a neuroprotective effect in patients who have experienced an aneurysmal subarachnoid hemorrhage (aSAH). Nimodipine remains the... (Review)
Review
INTRODUCTION: Enteral nimodipine provides a neuroprotective effect in patients who have experienced an aneurysmal subarachnoid hemorrhage (aSAH). Nimodipine remains the only US Food and Drug Administration-approved medication for aSAH. CONTENT: Nimodipine has been prescribed for patients with aSAH; however, little is known about factors to consider regarding dosing or patient-specific variables that may affect tolerability to nimodipine. Clinical impact of dose or dosing frequency changes has also been much debated based on risk of hypotension with currently approved dosing regimens. CONCLUSION: This review article addresses factors to consider for dosing and administration, pharmacokinetic and pharmacogenetic impact on nimodipine, and, finally, drug interaction considerations to assess as patients are initiated on enteral nimodipine for aSAH.
Topics: Calcium Channel Blockers; Clinical Protocols; Humans; Nimodipine; Pharmacogenetics; Subarachnoid Hemorrhage
PubMed: 34775392
DOI: 10.1097/JNN.0000000000000625 -
Healthcare Management Forum May 2020The use of pharmacogenetic information is becoming mainstream with insurance companies and others starting to pay for widescale implementation of this new technology...
The use of pharmacogenetic information is becoming mainstream with insurance companies and others starting to pay for widescale implementation of this new technology starting with patients who have anxiety and depression. It has been introduced in response to the unpredictability of medication, the high number of adverse drug events, and lack of drug effectiveness. Greater than one-third of patients are identified as having one or more pharmacogenetic variants. Each pharmacogenetic variant may affect the metabolism of several medications used in primary care, in addition to the antidepressant and anti-anxiolytic medications. Pharmacogenetic information is evolving with major international working groups providing continuous updates. It is challenging to incorporate this new information along with all the other variables needed to identify safe and effective drug options within a normal consultation. Medication decision support software is one solution that can help address this.
Topics: Cost-Benefit Analysis; Evidence-Based Medicine; Pharmacogenetics; Primary Health Care
PubMed: 32054324
DOI: 10.1177/0840470419901285 -
BMC Health Services Research Oct 2021Pharmacogenetics targets genetic variations that influence drug response. It is relatively a new science that has not been vastly employed in most developing countries...
BACKGROUND
Pharmacogenetics targets genetic variations that influence drug response. It is relatively a new science that has not been vastly employed in most developing countries including Syria. Therefore we aimed at evaluating the depth of knowledge in pharmacogenetics and the attitude towards it amongst Syrian pharmacists and physicians.
METHODS
We carried out an internet-based questionnaire consisted of 26 questions, sent through specialized websites and private groups with a large number of pharmacists and physicians members. The survey was available online for a period of 1 month.
RESULTS
The total number of respondents was 154, mostly female pharmacists. Our statistical analysis showed a strong positive association between profession (in favour of pharmacists) and pharmacogenetics knowledge p = 0.049; however, no correlation with experience p = 0.811 was found. A significant difference was reported between the knowledge of pharmacists and physicians p = 0.001 concerning drugs that need pharmacogenetics testing before being prescribed. The majority of respondents had no information about applying genetic tests in Syria before prescribing medications nor did they possess the knowledge regarding drugs that show differential responses in patients according to their unique genotypes. In our study, the percentage knowledge assessment score was low in general (mean ± Standard deviation, SD) (46% ± 13.9%). The majority of the respondents agreed that pharmacists should provide counselling to patients on the subject of pharmacogenetics. Respondents' opinions varied concerning making pharmacogenetics learning a priority.
CONCLUSION
Lack of pharmacogenetics knowledge was found amongst respondents in general. Our findings raise concerns about the lack of awareness amongst physicians, which may hinder the implementation of this crucial field in Syria. We suggest an emphasis on the role of education, training, and conducting genotyping research on the Syrian population.
Topics: Female; Health Knowledge, Attitudes, Practice; Humans; Male; Pharmacists; Pharmacogenetics; Physicians; Surveys and Questionnaires; Syria
PubMed: 34592972
DOI: 10.1186/s12913-021-07040-9 -
Annual Review of Genomics and Human... Aug 2022To embrace the prospects of accurately diagnosing thousands of monogenic conditions, predicting disease risks for complex traits or diseases, tailoring treatment to... (Review)
Review
To embrace the prospects of accurately diagnosing thousands of monogenic conditions, predicting disease risks for complex traits or diseases, tailoring treatment to individuals' pharmacogenetic profiles, and potentially curing some diseases, research into African genomic variation is a scientific imperative. African genomes harbor millions of uncaptured variants accumulated over 300,000 years of modern humans' evolutionary history, with successive waves of admixture, migration, and natural selection combining with extensive ecological diversity to create a broad and exceptional genomic complexity. Harnessing African genomic complexity, therefore, will require sustained commitment and equitable collaboration from the scientific community and funding agencies. African governments must support academic public research and industrial partnerships that build the necessary genetic medicine workforce, utilize the emerging genomic big data to develop expertise in computer science and bioinformatics, and evolve national and globalgovernance frameworks that recognize the ethical implications of data-driven genomic research and empower its application in African social, cultural, economic, and religious contexts.
Topics: Biological Evolution; Black People; Computational Biology; Genomics; Humans; Pharmacogenetics
PubMed: 35576571
DOI: 10.1146/annurev-genom-111521-102452 -
CNS Drugs Apr 2022The development of Alzheimer's disease therapeutics has been challenging, with 99% of clinical trials failing to find a significant difference between drug and placebo.... (Review)
Review
The development of Alzheimer's disease therapeutics has been challenging, with 99% of clinical trials failing to find a significant difference between drug and placebo. While the quest continues for more effective treatments, there is emerging evidence that pharmacogenetic considerations are important factors in regard to metabolism, efficacy, and toxicity of drugs. Currently, there are five US Food and Drug Administration-approved drugs for the treatment of Alzheimer's disease; three acetylcholinesterase inhibitors, memantine, and aducanumab. Introducing a limited genetic panel consisting of APOE4, CYP2D6*10, and BChE*K would optimize acetylcholinesterase inhibitor therapy, facilitate immunotherapy risk assessment, and inform an amyloid-related imaging abnormality surveillance schedule. In view of the genetic heterogeneity of Alzheimer's disease identified in genome-wide association studies, pharmacogenetics is expected to play an increasing role in mechanism-specific treatment strategies and personalized medicine.
Topics: Acetylcholinesterase; Alzheimer Disease; Apolipoprotein E4; Cholinesterase Inhibitors; Genome-Wide Association Study; Humans; Pharmacogenetics
PubMed: 35352296
DOI: 10.1007/s40263-022-00915-3 -
The Journal of Applied Laboratory... Jan 2024Pharmacogenetics or pharmacogenomics (PGx) is the study of the role of inherited or acquired sequence change in drug response. With the rapid evolution of molecular...
BACKGROUND
Pharmacogenetics or pharmacogenomics (PGx) is the study of the role of inherited or acquired sequence change in drug response. With the rapid evolution of molecular techniques, bioinformatic tools, and increased throughput of functional genomic studies, the discovery of PGx associations and clinical implementation of PGx test results have now moved beyond a handful variants in single pharmacogenes and multi-gene panels that interrogate a few pharmacogenes to whole-exome and whole-genome scales. Although some laboratories have adopted next-generation sequencing (NGS) as a testing platform for PGx and other molecular tests, most clinical laboratories that offer PGx tests still use targeted genotyping approaches.
CONTENT
This article discusses primarily the technical considerations for clinical laboratories to develop NGS-based PGx tests including whole-genome and whole-exome sequencing analyses and highlights the challenges and opportunities in test design, content selection, bioinformatic pipeline for PGx allele and diplotype assignment, rare variant classification, reporting, and briefly touches a few additional areas that are important for successful clinical implementation of PGx results.
SUMMARY
The accelerated speed of technology development associated with continuous cost reduction and enhanced ability to interrogate complex genome regions makes it inevitable for most, if not all, clinical laboratories to transition PGx testing to an NGS-based platform in the near future. It is important for laboratories and relevant professional societies to recognize both the potential and limitations of NGS-based PGx profiling, and to work together to develop a standard and consistent practice to maximize the variant or allele detection rate and utility of PGx testing.
Topics: Humans; Pharmacogenetics; Alleles; Computational Biology; High-Throughput Nucleotide Sequencing
PubMed: 38167765
DOI: 10.1093/jalm/jfad097 -
Pharmacogenetics and Genomics Feb 2022Evaluations from pharmacogenetics implementation programs at major US medical centers have reported variability in the clinical adoption of pharmacogenetics across...
OBJECTIVES
Evaluations from pharmacogenetics implementation programs at major US medical centers have reported variability in the clinical adoption of pharmacogenetics across therapeutic areas. A potential cause for this variability may involve therapeutic area-specific differences in published pharmacogenetics recommendations to clinicians. To date, however, the potential for differences in clinical pharmacogenetics recommendations by therapeutic areas from prominent US guidance sources has not been assessed. Accordingly, our objective was to comprehensively compare essential elements from clinical pharmacogenetics recommendations contained within Clinical Pharmacogenetics Implementation Consortium guidelines, US Food and Drug Administration drug labels and clinical practice guidelines from US professional medical organizations across therapeutic areas.
METHODS
We analyzed clinical pharmacogenetics recommendation elements within Clinical Pharmacogenetics Implementation Consortium guidelines, US Food and Drug Administration drug labels and professional clinical practice guidelines through 05/24/19.
RESULTS
We identified 606 unique clinical pharmacogenetics recommendations, with the most recommendations involving oncology (217 recommendations), hematology (79), psychiatry (65), cardiovascular (43) and anesthetic (37) medications. Within our analyses, we observed considerable variability across therapeutic areas within the following essential pharmacogenetics recommendation elements: the recommended clinical management strategy; the relevant genetic biomarkers; the organizations providing pharmacogenetics recommendations; whether routine genetic screening was recommended; and the time since recommendations were published.
CONCLUSIONS
On the basis of our results, we infer that observed differences in clinical pharmacogenetics recommendations across therapeutic areas may result from specific factors associated with individual disease states, the associated genetic biomarkers, and the characteristics of the organizations providing recommendations.
Topics: Genetic Markers; Genetic Testing; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 34412102
DOI: 10.1097/FPC.0000000000000452 -
Clinical Pharmacology and Therapeutics Nov 2023Precision medicine has evolved from the application of pharmacogenetic biomarkers to the prospective development of targeted therapies in patients with specific... (Review)
Review
Precision medicine has evolved from the application of pharmacogenetic biomarkers to the prospective development of targeted therapies in patients with specific molecular/genetic subtypes of disease to truly "N-of-1" medicines targeted to very small numbers of patients - in some cases, a single identified patient. This latter iteration of precision medicine presents unprecedented opportunities for patients with severe, life-threatening, or life-limiting diseases. At the same time, these modalities present complex scientific, clinical, and regulatory challenges. To realize the promise of individualized medicines, a multistakeholder approach to streamlining medical diagnoses, advancing the technologies that enable development of these therapeutic modalities, and re-envisioning collaborative environments for access and evidence generation is of critical importance. Herein, we highlight some of these challenges and opportunities.
Topics: Humans; Prospective Studies; Precision Medicine; Pharmacogenetics
PubMed: 37620252
DOI: 10.1002/cpt.3030 -
Cancer Treatment and Research 2023Cancer is the most challenging disease for medical professionals to treat. The factors underlying the complicated situation include anticancer drug-associated toxicity,...
Cancer is the most challenging disease for medical professionals to treat. The factors underlying the complicated situation include anticancer drug-associated toxicity, non-specific response, low therapeutic window, variable treatment outcomes, development of drug resistance, treatment complications, and cancer recurrence. The remarkable advancement in biomedical sciences and genetics, over the past few decades, however, is changing the dire situation. The discovery of gene polymorphism, gene expression, biomarkers, particular molecular targets and pathways, and drug-metabolizing enzymes have paved the way for the development and provision of targeted and individualized anticancer treatment. Pharmacogenetics is the study of genetic factors having the potential to affect clinical responses and pharmacokinetic and pharmacodynamic behaviors of drugs. This chapter emphasizes pharmacogenetics of anticancer drugs and its applications in improving treatment outcomes, selectivity, toxicity of the drugs, and discovering and developing personalized anticancer drugs and genetic methods for prediction of drug response and toxicity.
Topics: Humans; Pharmacogenetics; Precision Medicine; Antineoplastic Agents
PubMed: 37306909
DOI: 10.1007/978-3-031-27156-4_9