pharmacogenetics lect 9 Flashcards Preview

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Flashcards in pharmacogenetics lect 9 Deck (18):
1

neutral mutation

changes the amino acid sequence of a protein without altering its ability to function

Ex: acidic amino acid is replaced with another acidic amino acid 

2

90% of all human genetic variation comes from what

SNPs

3

missense mutation

 a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid

4

nonsense mutation

a point mutation in a sequence of DNA that results in a premature stop codon

5

what are pharmacogenetically-important mutations

any mutation that

  • changes gene copy number (gene duplication or deletion)
  • changes function of the protein
  • can have pharmacological consequences 

6

what is an example of a change in protein function

NAT2

7

what is the function of NAT2

  • Transfers an acetyl group from acetyl-CoA to the acceptor amine resulting in formation of an amide on the drug.

8

NAT2 is Involved in the metabolism of the following drugs:

Isoniazid, hydralazine, procainamide

**Genetic variation in NAT2 results in striking differences in the half-life and plasma concentrations of drugs metabolized by NAT2

9

a single isozymic variant of the NAT creates what two divisions of liver metabolism

fast and slow Acetylators

*individuals are identified as a rapid or slow acetylator by determining plasma concentration of a test drug (such as isoniazid) at a specified time after administering a fixed dose

10

Phenotypic slow acetylators have what alleles

rr

11

Phenotypic rapid acetylators have what alleles

may be either homozygous or heterozygous for the rapid allele (R/R or R/r)

*rapid allele is dominant

12

Adverse effects are related to the rate of acetylation of the drugs procainamide, hydralzaine via the slow allele (slow NAT activity) gives rise to what disease

Lupus

*slow rate of acetylation means drug is around longer in the body

13

Adverse effects are related to the rate of acetylation of isoniazid via the rapid allele (rapid NAT activity) gives rise to what condition

hepatotoxicity

14

what is a gene copy number example 

CYP2D6

15

what is the first and second most common metabolizing enzyme

  1. CYP3A4
  2. CYP2D6
    1. has >90 alleles that will make a patient be a 
      1. poor metabolizer
      2. intermediate metabolizer
      3. (extensive) normal metabolizer
      4. ultrarapid metabolizer 

16

CYP2D6 is involved in the metabolism of the following drugs:

codeine. fluoxetine, oxycodone, tricyclic antidepressants

17

what are microarrays

"gene chips"

  • have the ability to measure gene expression level
  • identify alleles

18

name two current microarrays

  1. roche amplichip: looks at gene variations in CYP2D6 and CYP2C19 genes
  2. Affymetrix DMET plus panel