Pathology and Laboratory Medicine Book

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Pharmacology

  • Genetic Determinants of Drug Response

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Genetic Determinants of Drug Response

Aka: Genetic Determinants of Drug Response, Pharmacogenomics, Pharmacogenetics
  1. See Also
    1. Genetics
  2. Definition
    1. Genetic Polymorphism as it relates to medication response
  3. Examples: Cytochrome P450 genetic variants
    1. CYP2D6Gene Variants
      1. Poor metabolizers (5-10%)
        1. No response (or reduced response) to Codeine, Tramadol
        2. Fluoxetine and Nortriptyline risk of toxicity
        3. Amitriptyline, Nortriptyline, Paroxetine risk of toxicity (reduce starting dose by 50%)
        4. Aripiprazole (Abilify) risk of toxicity (reduce starting dose)
        5. Atomoxetine (Strattera) risk of toxicity (reduce starting dose)
      2. Ultra-metabolizers (1-2%)
        1. Codeine risk of toxicity (deaths have occurred)
        2. Amitriptyline, Nortriptyline, Paroxetine with reduced response (consider other agents)
    2. CYP2C19Gene Variants
      1. Poor metabolizers (2-15%)
        1. Clopidogrel with reduced conversion to active form (higher risk for stent closure)
        2. Amitriptyline and Nortriptyline risk of toxicity (reduce starting dose by 50%)
        3. Citalopram, Escitalopram, Sertraline risk of toxicity (reduce starting dose by 50%)
      2. Ultra-Metabolizers
        1. Citalopram, Escitalopram, Sertraline with reduced effect (consider alternative agents)
    3. CYP2C9Gene Variants
      1. Poor metabolizers
        1. Reaching a steady-state INR on Coumadin requires >3 months
          1. Higher risk of toxicity and bleeding complications
  4. Examples: HLA Variants
    1. HLA-B*1502
      1. Carbamazepine induced Stevens–Johnson syndrome risk in asian patients (test before use)
    2. HLA-B*5701
      1. Abacavir (HIV agent) induced hypersensitivity risk in HLA-B*5701 positive patients
  5. Examples: Miscellaneous genetic variants
    1. TPMT Deficiency
      1. Severe hematologic response to Azathioprine and mercaptopurine
    2. ADRB2 Variant
      1. Asthma status worsens on Inhaled Beta Agonist (e.g. Albuterol)
  6. Efficacy
    1. Pharmacogenetic testing is indicated in specific cases
    2. Broader screening for pharmacogenetic variation is not yet supported by the Medical Literature in 2015
      1. Wang (2014) JAMA Intern Med 174(12):1938-44 +PMID:25317785 [PubMed]
  7. References
    1. (2015) Presc Lett 22(9): 51
    2. Chang (2015) Am Fam Physician 92(7): 588-94 [PubMed]
    3. Evans (2003) N Engl J Med 348:538-49 [PubMed]
    4. Lanfear (2007) Am Fam Physician 76:1179-82 [PubMed]
    5. Meyer (2000) Lancet 356:1667-71 [PubMed]

Pharmacogenetics (C0031325)

Definition (NCI) The investigation of the influence of variations in DNA sequence on drug response.
Definition (NCI_NCI-GLOSS) The study of how a person's genes affect the way he or she responds to drugs. Pharmacogenetics is being used to learn ahead of time what the best drug or the best dose of a drug will be for a person.
Definition (NCI_CDISC) Study of the way drugs interact with genetic makeup or the study of genetic response to a drug.
Definition (MSH) A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION).
Definition (CSP) branch of genetics (the branch of science concerned with the means and consequences of transmission and generation of the components of biological inheritance) which deals with the genetic variability in individual responses to drugs and drug metabolism.
Concepts Biomedical Occupation or Discipline (T091)
MSH D010597
Swedish Farmakogenetik
English PHARMACOGENET, PGt, Pharmacogenetics, pharmacogenetic, pharmacogenetics
Czech farmakogenetika
Finnish Farmakogenetiikka
French Pharmaco-génétique, Pharmacologie génétique, Pharmacogénétique
Russian FARMAKOGENETIKA, ФАРМАКОГЕНЕТИКА
Croatian FARMAKOGENETIKA
Polish Farmakogenetyka
Norwegian Farmakogenetikk
German Pharmakogenetik
Italian Farmacogenetica
Dutch Farmacogenetica
Portuguese Farmacogenética
Spanish Farmacogenética
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Pharmacogenomics Domain (C1882354)

Definition (NCI_CDISC) Pharmacogenomics findings that initially focus on genotype and gene expression data.
Definition (NCI) A subject domain utilized for the submission of information encompassing and representing data, vocabulary or records related to pharmacogenomics.
Concepts Idea or Concept (T078)
English Pharmacogenomics Domain, Pharmacogenomics/Genetics Methods and Supporting Information, PG
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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