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Pharmacology Basic Principles > Pharmacogenetics > Flashcards

Flashcards in Pharmacogenetics Deck (14):
1

Pharmacogenetic vs. pharmacogenomics

Genetic basis for variation in drug response include genomics which surveys the genome entirely to asses genetic diversity

2

6-mercaptopurine example

Treats childhood acute lymphoblastic leukemia. 1 in 100 children have a variant thiopurine methyltransferase, which prevents 6-MP metabolism drug accumulates to fatal result. Now all children are screened before 6-MP administration

3

Poor metabolizers of Clopidogrel example

Anticoagulant, variant CYP2C19 with poor activity results in low active species in plasma. Treatment failure. test for poor metabolism - probe substrate or genetic screen.

4

Phenotype to Genotype

Evaluate drug metabolizer outliers and determine genetic polymorphisms. Historical method

5

Genotype to Phenotype

Scan genome, identify polymorphisms, determine if they translate to phenotypic activity

6

Monogenic trait example

CYP2D6 poor metabolizer

7

Multigenic traits

harder to predict phenotype, and a continuum of phenotypes are present - classic dominance patterns breakdown

8

Polymorphisms

variation in DNA sequence that is present in 1% or greater in the population. SNP, Insertions/Deletions, and Copy number variation

9

cSNP

coding SNP: Missense (non-synonymous) - amino acid change. Sense (synonymous) - no amino acid change (can still change phenotype). Nonsense - early stop codon

10

SNP in non-coding region

Can result in translatability, stability, splicing, DNA tertiary structure and replication

11

Haplotype

Set of SNP on single chromosome that is statistically associated.

12

Linkage

Equilibrium - independent, disequilibrium - not independent, complete disequilibrium - genotype at 2 loci always occur together

13

NAT2 example

Catalyzes N-acetylation of a large number of drugs (procainamide, caffeine, etc.) Considerable ethnic variation. Slow acetylators - increased risk of polyneuropathy with isoniazid, increase risk of bladder cancer, hemolytic anemia with sulfa drugs. Fast acetylators need more drug for therapeutic effect. Fast activity is dominant

14

Alcohol Dehydrogenase

ADH2 variant convert alcohol to down stream substrates faster leading to flushing with alcohol consumption.