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Related Concept Videos

Pharmacogenetics and Pharmacogenomics: Overview01:29

Pharmacogenetics and Pharmacogenomics: Overview

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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...
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Principles of Pharmacogenetics: Types of Genetic Variants01:27

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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...
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Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

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

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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 Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

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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...
194
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

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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...
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Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

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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...
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The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation
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A pharmacogenetic versus a clinical algorithm for warfarin dosing.

Stephen E Kimmel1, Benjamin French, Scott E Kasner

  • 1The authors' affiliations are listed in the Appendix.

The New England Journal of Medicine
|November 21, 2013
PubMed
Summary
This summary is machine-generated.

Genotype-guided warfarin dosing did not improve anticoagulation control in most patients. This pharmacogenetic approach showed no benefit in maintaining the international normalized ratio (INR) within the therapeutic range during initial therapy.

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Area of Science:

  • Pharmacogenomics
  • Clinical Pharmacology
  • Internal Medicine

Background:

  • The clinical utility of genotype-guided warfarin dosing remains uncertain due to limited evidence from small trials.
  • Previous studies have yielded equivocal results regarding the effectiveness of pharmacogenetic warfarin dosing.

Purpose of the Study:

  • To evaluate the efficacy of genotype-guided warfarin dosing compared to clinically guided dosing in achieving therapeutic anticoagulation.
  • To determine if incorporating genetic data into warfarin dosing algorithms improves anticoagulation control.

Main Methods:

  • A randomized trial involving 1015 patients comparing genotype-guided warfarin dosing with clinically guided dosing.
  • Warfarin doses were determined using algorithms including clinical variables and/or genotype data.
  • The primary outcome was the percentage of time the international normalized ratio (INR) was within the therapeutic range during the first 4 weeks of therapy.

Main Results:

  • Genotype-guided dosing did not significantly improve the percentage of time in the therapeutic INR range compared to clinical dosing (45.2% vs. 45.4%).
  • A significant interaction was observed based on race, with lower therapeutic range achievement in Black patients receiving genotype-guided doses.
  • No significant differences were found in major bleeding or thromboembolism rates between the groups.

Conclusions:

  • Genotype-guided warfarin dosing did not enhance anticoagulation control in the initial 4 weeks of therapy.
  • The effectiveness of genotype-guided warfarin dosing may vary across different racial groups.
  • Further research is needed to clarify the role of pharmacogenetics in warfarin therapy.