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British Journal of Clinical Pharmacology Apr 2014Because of the large variation in the response to psychoactive medication, many studies have attempted to uncover genetic factors that determine response. While... (Review)
Review
Because of the large variation in the response to psychoactive medication, many studies have attempted to uncover genetic factors that determine response. While considerable knowledge exists on the large effects of genetic polymorphisms on pharmacokinetics and plasma concentrations of drugs, effects of the concentration at the target site and pharmacodynamic effects on brain functions in disease are much less known. This article reviews the role of magnetic resonance imaging (MRI) to visualize response to medication in brain behaviour circuits in vivo in humans and assess the influence of pharmacogenetic factors. Two types of studies have been used to characterize effects of medication and genetic variation. In task-related activation studies the focus is on changes in the activity of a neural circuit associated with a specific psychological process. The second type of study investigates resting state perfusion. These studies provide an assessment of vascular changes associated with bioavailability of drugs in the brain, but may also assess changes in neural activity after binding of centrally active agents. Task-related pharmacogenetic studies of cognitive function have characterized the effects in the prefrontal cortex of genetic polymorphisms of dopamine receptors (DRD2), metabolic enzymes (COMT) and in the post-synaptic signalling cascade under the administration of dopamine agonists and antagonists. In contrast, pharmacogenetic imaging with resting state perfusion is still in its infancy. However, the quantitative nature of perfusion imaging, its non-invasive character and its repeatability might be crucial assets in visualizing the effects of medication in vivo in man during therapy.
Topics: Brain; Cognition; Dopamine Agonists; Functional Neuroimaging; Humans; Inactivation, Metabolic; Magnetic Resonance Imaging; Pharmacogenetics; Polymorphism, Genetic; Psychomotor Performance
PubMed: 23802603
DOI: 10.1111/bcp.12197 -
Methods in Molecular Biology (Clifton,... 2013The Pharmacogenomics Knowledge Base, PharmGKB, is an interactive tool for researchers investigating how genetic variation affects drug response. The PharmGKB Web site,...
The Pharmacogenomics Knowledge Base, PharmGKB, is an interactive tool for researchers investigating how genetic variation affects drug response. The PharmGKB Web site, http://www.pharmgkb.org , displays genotype, molecular, and clinical knowledge integrated into pathway representations and Very Important Pharmacogene (VIP) summaries with links to additional external resources. Users can search and browse the knowledgebase by genes, variants, drugs, diseases, and pathways. Registration is free to the entire research community, but subject to agreement to use for research purposes only and not to redistribute. Registered users can access and download data to aid in the design of future pharmacogenetics and pharmacogenomics studies.
Topics: Algorithms; Databases, Genetic; Humans; Internet; Knowledge Bases; Pharmacogenetics
PubMed: 23824865
DOI: 10.1007/978-1-62703-435-7_20 -
The American Journal of Geriatric... Feb 2018Clinicians still employ a "trial-and-error" approach to optimizing treatment regimens for late-life depression (LLD). With LLD affecting a significant and growing... (Review)
Review
Clinicians still employ a "trial-and-error" approach to optimizing treatment regimens for late-life depression (LLD). With LLD affecting a significant and growing segment of the population, and with only about half of older adults responsive to antidepressant therapy, there is an urgent need for a better treatment paradigm. Pharmacogenetic decision support tools (DSTs), which are emerging technologies that aim to provide clinically actionable information based on a patient's genetic profile, offer a promising solution. Dozens of DSTs have entered the market in the past 15 years, but with varying level of empirical evidence to support their value. In this clinical review, we provide a critical analysis of the peer-reviewed literature on DSTs for major depression management. We then discuss clinical considerations for the use of these tools in treating LLD, including issues related to test interpretation, timing, and patient perspectives. In adult populations, newer generation DSTs show promise for the treatment of major depression. However, there are no primary clinical trials in LLD cohorts. Independent and comparative clinical trials are needed.
Topics: Aging; Decision Support Techniques; Depressive Disorder, Major; Humans; Pharmacogenetics; Precision Medicine
PubMed: 29429869
DOI: 10.1016/j.jagp.2017.05.012 -
The Pharmacogenomics Journal Mar 2022Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to... (Meta-Analysis)
Meta-Analysis Review
Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to healthcare delivery is required. Pharmacogenetics has potential as a component of medicines optimisation. Studies involving multi-medicine pharmacogenetics in adults with multimorbidity or polypharmacy, reporting on outcomes derived from relevant core outcome sets, were included in this systematic review. Narrative synthesis was undertaken to summarise the data; meta-analysis was inappropriate due to study heterogeneity. Fifteen studies of diverse design and variable quality were included. A small, randomised study involving pharmacist-led medicines optimisation, including pharmacogenetics, suggests this approach could have significant benefits for patients and health systems. However, due to study design heterogeneity and the quality of the included studies, it is difficult to draw generalisable conclusions. Further pragmatic, robust pharmacogenetics studies in diverse, real-world patient populations, are required to establish the benefit of multi-medicine pharmacogenetic screening on patient outcomes.
Topics: Humans; Multimorbidity; Pharmacists; Pharmacogenetics; Pharmacogenomic Testing; Polypharmacy
PubMed: 35194175
DOI: 10.1038/s41397-021-00260-6 -
American Journal of Pharmaceutical... Apr 2019To evaluate students' knowledge, confidence, and skills after implementation of an active-learning laboratory session in clinical pharmacogenetics. Third-year pharmacy...
To evaluate students' knowledge, confidence, and skills after implementation of an active-learning laboratory session in clinical pharmacogenetics. Third-year pharmacy students (n=130) participated in an active-learning laboratory session on pharmacogenetics. In the laboratory activity, students evaluated patients' pharmacogenetic profiles and documented recommendations to providers based on their findings. Students also counseled a simulated patient on the interpretation of their pharmacogenetic profile. Students' knowledge and confidence were assessed before a lecture on clinical pharmacogenetics, after the lecture, and then after the laboratory activity. The assessment included 10 knowledge-based questions and five confidence questions regarding clinical pharmacogenetics. An evaluation of the laboratory activity was completed after the session. On average, students correctly answered 70.3% of the knowledge-based questions before the lecture, 82.8% after the lecture, and 88.7% after the laboratory session. Additionally, students' confidence improved in each of the five areas assessed. Based on evaluations (response rate: 98.5%), students found that the laboratory activity contributed to their professional development, was taught at an appropriate level for their understanding, and was relevant to pharmacy practice. An active-learning laboratory session to teach pharmacy students about clinical pharmacogenetics improved students' knowledge, confidence, and skills.
Topics: Clinical Competence; Curriculum; Education, Pharmacy; Educational Measurement; Humans; Knowledge; Patient Simulation; Pharmacogenetics; Problem-Based Learning; Program Evaluation; Students, Pharmacy
PubMed: 31065165
DOI: 10.5688/ajpe6605 -
Current Opinion in Cardiology May 2014Novel medical approaches and personalized medicine seek to use genetic information to 'individualize' and improve diagnosis, prevention, and therapy. The personalized... (Review)
Review
PURPOSE OF REVIEW
Novel medical approaches and personalized medicine seek to use genetic information to 'individualize' and improve diagnosis, prevention, and therapy. The personalized management of cardiovascular disease involves a large spectrum of potential applications, from diagnostics of monogenic disorders, to prevention and management strategies based on modifier genes, to pharmacogenetics, in which individual genetic information is used to optimize the pharmacological treatments.
RECENT FINDINGS
Evidence suggests that the common polymorphic variants of modifier genes could influence drug response in cardiovascular disease in a variety of areas, including heart failure, arrhythmias, dyslipidemia, and hypertension. In heart failure, common genetic variants of β-adrenergic receptors, α-adrenergic receptors, and endothelin receptors (among others) have been associated with variable response to heart failure therapies. The challenge remains to develop strategies to leverage this information in ways that personalize and optimize cardiovascular therapy based on a patient's genetic profile.
SUMMARY
Although advances in technologies will continue to transition personalized medicine from the research to the clinical setting, healthcare providers will need to reshape the clinical diagnostic paradigms. Ultimately, pharmacogenetics will give providers the options for improving patient management on the basis of pharmacogenetic data.
Topics: Cardiovascular Agents; Disease Management; Genetic Variation; Heart Failure; Humans; Pharmacogenetics; Precision Medicine; Receptors, Adrenergic; Receptors, Endothelin
PubMed: 24717669
DOI: 10.1097/HCO.0000000000000056 -
Seminars in Hematology Jan 2009Progress in the treatment of acute lymphoblastic leukemia (ALL) in children has been remarkable, from a disease being lethal four decades ago to current cure rates... (Review)
Review
Progress in the treatment of acute lymphoblastic leukemia (ALL) in children has been remarkable, from a disease being lethal four decades ago to current cure rates exceeding 80%. This exemplary progress is largely due to the optimization of existing treatment modalities rather than the discovery of new antileukemic agents. However, despite these high cure rates, the annual number of children whose leukemia relapses after their initial therapy remains greater than that of new cases of most types of childhood cancers. The aim of pharmacogenetics is to develop strategies to personalize treatment and tailor therapy to individual patients, with the goal of optimizing efficacy and safety through better understanding of human genome variability and its influence on drug response. In this review, we summarize recent pharmacogenomic studies related to the treatment of pediatric ALL. These studies illustrate the promise of pharmacogenomics to further advance the treatment of human cancers, with childhood leukemia serving as a paradigm.
Topics: Antineoplastic Agents; Child; Child, Preschool; Computational Biology; Gene Expression Profiling; Humans; Mutation; Pharmacogenetics; Polymorphism, Genetic; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 19100367
DOI: 10.1053/j.seminhematol.2008.09.002 -
British Journal of Clinical Pharmacology Apr 2014Pharmacogenomics, the study of variations of DNA and RNA characteristics as related to drug response, has become an integral part of drug development and... (Review)
Review
Pharmacogenomics, the study of variations of DNA and RNA characteristics as related to drug response, has become an integral part of drug development and pharmacovigilance, as reflected by the incorporation of pharmacogenomic data in EU product information. In this short review article, we describe recent European Medicines Agency initiatives intended to support further the implementation of pharmacogenomics in drug development and surveillance so that patients and the public can benefit from advances in genomic science and technology.
Topics: Drug Discovery; Europe; Guidelines as Topic; Humans; Pharmacogenetics; Pharmacovigilance
PubMed: 24433361
DOI: 10.1111/bcp.12319 -
Annals of the Academy of Medicine,... Aug 2011There have been several success stories in the field of pharmacogenetics in recent years, including the analysis of HER2 amplification for trastuzumab selection in...
There have been several success stories in the field of pharmacogenetics in recent years, including the analysis of HER2 amplification for trastuzumab selection in breast cancer and VKORC1 genotyping for warfarin dosing in thrombosis. Encouraging results from these studies suggest that genetic factors may indeed be important determinants of drug response and toxicity for at least some drugs. However, to apply pharmacogenetics appropriately, a thorough understanding of the scope and limitations of this field is required. The challenges include an appreciation of biological variability, logistical issues pertaining to the proper management of information, the need for robust methods and adequate sample quality with well-designed workflows. At the same time, the economics of pharmacogenetic testing from the perspective of clinicians, patients, governments, insurance companies and pharmaceutical companies will play an important role in determining its future use. Ethical considerations such as informed consent and patient privacy, as well as the role of regulatory bodies in addressing these issues, must be fully understood. Only once these issues are properly dealt with can the full benefits of pharmacogenetics begin to be realised.
Topics: Antineoplastic Agents; Genetic Privacy; Humans; Informed Consent; Neoplasms; Pharmacogenetics; Translational Research, Biomedical
PubMed: 22065003
DOI: No ID Found -
Human Genetics May 2015Understanding the role genes and genetic variants play in clinical treatment response continues to be an active area of research with the goal of common clinical use.... (Review)
Review
Understanding the role genes and genetic variants play in clinical treatment response continues to be an active area of research with the goal of common clinical use. This goal has developed into today's industry of pharmacogenomics, where new drug-gene relationships are discovered and further characterized, published and then curated into national and international resources for use by researchers and clinicians. These efforts have given us insight into what a pharmacogenomic variant is, and how it differs from human disease variants and common polymorphisms. While publications continue to reveal pharmacogenomic relationships between genes and specific classes of drugs, many challenges remain toward the goal of widespread use clinically. First, the clinical guidelines for pharmacogenomic testing are still in their infancy. Second, sequencing technologies are changing rapidly making it somewhat unclear what genetic data will be available to the clinician at the time of care. Finally, what and when to return data to a patient is an area under constant debate. New innovations such as PheWAS approaches and whole genome sequencing studies are enabling a tsunami of new findings. In this review, pharmacogenomic variants, pharmacogenomic resources, interpretation clinical guidelines and challenges, such as WGS approaches, and the impact of pharmacogenomics on drug development and regulatory approval are reviewed.
Topics: Computational Biology; Data Interpretation, Statistical; Databases, Genetic; Databases, Pharmaceutical; Drug Discovery; Genetic Variation; Humans; Pharmacogenetics; Phenotype
PubMed: 25238897
DOI: 10.1007/s00439-014-1484-7