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Pharmacogenetics
Exam #3 info
16
Pharmacology
Graduate
04/26/2010

Additional Pharmacology Flashcards

 


 

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Term
Pharmacogenetics
Definition

  • The study of how an individuals genetic inheritance affects the body's response to drugs
  • inter-individual differences seen in genes that encode drug targets, drug transporters, or enzymes that catalyze drug metabolism
  • Genetic make-up cold be used to enhance pharmacotherapy, maximize drug efficacy , and/or reduce incidence of side effects

Term
common factors affecting drug response
Definition

  • Age
  • Gender
  • Body size
  • Disease state/ body system function
  • drug or dietary interactions
  • hypoalbuminemia
  • fever, stress, exercise
  • pregnancy
  • Genetic Factors

Term
Polymorphisms
Definition
changes in the DNA base-pair composition of genes
Term
pharmacogenomic variations
Definition

  1. variations in enzymes of drug metabolism (affect pharmacokinetics) e.g. CYP450
  2. Variations in drug targets (affect pharmacodynamics) e.g. receptors
  3. Idiosyncratic drug reactions (everything else)

Term
Polymorphism in CYP450 enzymes
Definition

  • CYP3A4 involved in 40-45% of drug metabolism, but polymorphisms are rare
  • CYP2D6 gene is extremely polymorphic with > 70 allelic variants described. CYP2D6 is involved in 20-30% of drug metabolism
  • CYP2C19, and CYP2C9 are also know to have polymorphisms 

Term
impact of polymorphism on drug metabolism for active drugs
Definition

 

  • Ultra-rapid metabolizer: no drug response at ordinary dosage (non-responders)
  • Extensive metabolizer: Expected response to standard dose
  • Intermediate metabolizer: may experience a lesser degree of consequences of poor metabolizers
  • Poor metabolizer: Too slow or no drug metabolism
    • too high drug levels at usual doses
    • high risk for adverse drug rxns (toxicity)

 

Term

impact of polymorphism on drug metabolism for pro-drugs

Definition

the opposite phenomenon as that with active drug occurs.

Ultra-rapid metabolizers may suffer adverse events and poor metabolizers may not respond

Term
Drugs effected by pharmacogenetics 
Definition

Clopidogrel (CYP3A)

Warfarin (CYP2C9)

 

many others such as NSAIDS, some beta blockers, codeine, ethanol, some PPIs, some antidepressants...

Term
Variations in drug targets (receptors)
Definition

  • Drugs exert their effects by interacting with specific target proteins
  • Genetic variations in target proteins can influence the outcome of pharmacotherapy
  • examples:
    • ACEI (e.g lisinopril)
    • Epidermal growth factor receptors (e.g. gefitinib)
    • Vitamin K epoxide reductase complex 1 (e.g. warfarin)
    • Apolipoprotein E (e.g. pravastatin)

 

Term
Examples of genetic polymorphism and drug targets
Definition

 

  • ACEI (e.g lisinopril)
  • Epidermal growth factor receptors (e.g. gefitinib)
  • Vitamin K epoxide reductase complex 1 (e.g. warfarin)
  • Apolipoprotein E (e.g. pravastatin)

 

Term
ACE gene polymorphism
Definition

 

  • affects response to lisinopril
  • enhanced renoprotective effects

 

Term
β2 adrenergic receptor polymorphism
Definition

 

  • affects response to Albuterol
  • increased forced expiratory volume in one second (FEV1)

 

Term
Genetic polymorphism in epidermal growth factor receptor (EGFR)
Definition

 

  • affects response to Gefitinib
  • more favorable response
  • majority of human epithelial cancers are marked by functional activation of growth factors and receptors of the epidermal growth factor receptor (EGFR) family
  • EGFR was the first growth factor receptor to be proposed as a target for cancer therapy
  • in pts with non-small cell lung cancer (NSCLC) response to EGFR inhibitor gefitinib was strongly influenced by somatic mutations that affect receptor binding

 

Term
Idiosyncratic drug reactions
Definition

  • Difficult or impossible to predict. Pharmacogenetics may help screen for unanticipated drug reactions
  • least predictable effect of inter-individual genetic variation
  • e.g. G6PD deficiency
  • result from interaction between medication and pts unique physiology

Term
Potential benefits of pharmacogenetics
Definition

 

  • maximize drug efficacy
  • minimize toxicity by refining drug dosing
  • reduce time to efficacious dose
  • development of drugs that maximize therapeutic effects but decrease damage to nearby healthy cells
  • manufacture more powerful medications
  • predicts most suitable drug

 

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