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Pharmacogenetics and Pharmacogenomics: Overview01:29

Pharmacogenetics and Pharmacogenomics: Overview

Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450 isoenzymes,...

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Editors' report, November 2010.

British journal of clinical pharmacology·2010
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Evolution of pharmacogenomics.

Andrew Somogy1

  • 1Discipline of Pharmacology, School of Medical Sciences, Faculty of Health Sciences, University of Adelaide, Australia. andrew.somogyi@adelaide.edu.au

Proceedings of the Western Pharmacology Society
|June 24, 2009
PubMed
Summary

Pharmacogenetics and pharmacogenomics explore genetic variations influencing drug response. While advancements offer personalized medicine, clinical adoption faces challenges from cost, environmental factors, and education.

Area of Science:

  • Genetics
  • Pharmacology
  • Personalized Medicine

Background:

  • Pharmacogenetics, with roots in ancient observations, formally emerged in the 1950s with enzyme polymorphism discoveries.
  • The field experienced a resurgence with the identification of CYP2D6 polymorphism in the 1970s, linking genetics to drug response and pharmacokinetics.
  • The advent of genotyping technologies led to the broader term pharmacogenomics, encompassing a growing number of genes affecting drug metabolism, transport, and receptors.

Purpose of the Study:

  • To review the historical development and current state of pharmacogenetics and pharmacogenomics.
  • To highlight the increasing identification of gene polymorphisms associated with variable drug responses.
  • To discuss the challenges and future directions for translating pharmacogenetic findings into clinical practice and personalized medicine.

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Main Methods:

  • Historical review of pharmacogenetics and pharmacogenomics.
  • Analysis of gene polymorphisms impacting drug response at enzyme, transporter, and receptor levels.
  • Discussion of genome-wide association studies and their contribution to identifying new relevant genes.

Main Results:

  • Numerous gene polymorphisms are now known to influence drug efficacy and toxicity.
  • Genome-wide analyses are uncovering novel genes associated with disease and drug response.
  • Clinical translation has primarily focused on narrow therapeutic index drugs, with limited broader adoption.

Conclusions:

  • Pharmacogenomics holds promise for personalized medicine, driven by advances in whole genome sequencing and data analysis.
  • Widespread clinical adoption is hindered by factors including clinical relevance, environmental-gene interactions, cost, and education.
  • Integrating pharmacogenetic insights into individualized dosage recommendations requires overcoming significant translational barriers.