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Related Concept Videos

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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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...
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Venous thrombosis requires effective prevention and treatment strategies to improve patient outcomes and reduce potential complications.Prevention StrategiesHealthcare providers must prioritize preventing venous thromboembolism (VTE) for all adult patients upon admission. Interventions depend on bleeding and thrombosis risk, medical history, current medications, diagnoses, planned procedures, and patient preferences. Patients on bed rest should change positions every two hours and, if not...
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Therapeutic Drug Monitoring: Affecting Factors

Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.

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Related Experiment Video

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The Nijmegen Hemostasis Assay: Simultaneous Fluorogenic Measurement of Thrombin and Plasmin Generation in a Single Well
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Genetic testing for warfarin therapy initiation.

Lauren M Hynicka1, William D Cahoon, Bonny L Bukaveckas

  • 1Virginia Commonwealth University Health System, Medical College of Virginia Hospitals, Richmond, VA 23298, USA. lhynicka@mcvh-vcu.edu

The Annals of Pharmacotherapy
|August 7, 2008
PubMed
Summary

Genetic testing for warfarin dosing, including CYP2C9 and VKORC1 genotypes, does not improve safety or efficacy. Current literature does not support routine pharmacogenomic testing for initiating warfarin therapy.

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Published on: April 1, 2019

Area of Science:

  • Pharmacogenomics
  • Clinical Pharmacology
  • Genetics

Background:

  • Warfarin anticoagulation therapy presents challenges in achieving therapeutic international normalized ratio (INR).
  • Genetic variations in CYP2C9 and VKORC1 influence warfarin metabolism and dose requirements.
  • Interindividual variability in warfarin response necessitates careful dose titration.

Purpose of the Study:

  • To review the literature on the efficacy of genetic testing for warfarin dose determination.
  • To assess the impact of pharmacogenomic testing on warfarin therapy safety and efficacy.

Main Methods:

  • Systematic literature search of MEDLINE and Cochrane Database (1966-May 2008).
  • Inclusion of English-language studies on human subjects evaluating pharmacogenomic testing for warfarin initiation.
  • Data synthesis from four eligible studies.

Main Results:

  • Four studies evaluated genetic testing for initial warfarin dosing.
  • No significant differences were observed in time to therapeutic INR or stable dose between genotype-guided and conventional dosing.
  • Time within the target INR range was similar (approximately 41.5%) for both conventional and pharmacogenomic-based dosing strategies.

Conclusions:

  • Variant alleles of CYP2C9 and VKORC1 contribute to warfarin dose variability.
  • Current evidence does not demonstrate improved safety or efficacy outcomes with pharmacogenomic testing for initiating warfarin therapy.
  • Routine use of pharmacogenomic testing for warfarin initiation is not supported by available literature.