9: Toxicogenomics

Question 1

genome wide response- study of how interacting systems of genes determine individual drug response (the right drug for the right disease)

Answer 1

pharmacogenomics

Question 2

study of how variant forms of human genes contribute to interindividual variability in drug response (the right drug for the right patient)

Answer 2

pharmacogenetics

Question 3

deals with AEs of toxins/ poisons due to genetic differences of the individual that impacts the response

Answer 3

toxicogenomics/ toxicogenetics

Question 4

warfarin is metabolized by

Answer 4

CYP2C9

Question 5

__ warfarin is 3-5x more potent than ___ warfarin

Answer 5

S >R

Question 6

clopidogrel is metabolized by

Answer 6

CYP2C19, CYP3A

Question 7

clopidogrel prevents platelet aggregation by

Answer 7

Targets P2Y12 receptor and glycoprotein IIB/IIa receptor

Question 8

codeine is metabolized to morphine by

Answer 8

CYP2D6

Question 9

what would happen if you gave codeine to an ultrarapid metabolizer

Answer 9

would have abdominal pain as an AE to morphine

Question 10

what would happen if you have codeine to a poor motabolizer

Answer 10

no analgesia from lack of conversion to morphine

Question 11

how does the HLA system work

Answer 11

they encode a cell surface protein that binds peptides generated by proteolysis, then presents them to T cells while going to cell surface

Question 12

why are there hypersensitivity reactions and inappropriate immune responses from the HLA system

Answer 12

HLA proteins are highly polymorphic= can result in hLA-protein complex the T cell sees as nonself = T cell response = type 4 reaction

Question 13

HLA gene located on chromosome ___

Answer 13

6

Question 14

which HLA genes are the most highly polymorphic?

Answer 14

A, B, C

Question 15

SNPs in a single gene associated with altered drug metabolism or drug effects

Answer 15

single gene effects

Question 16

most drug eff determined to be interplay of several gene products- multiple genes involved in PK/PD of drugs

Answer 16

multigene effects

Question 17

what is an example of polygenic response

Answer 17

Synergistic polymorphisms of B1 and a2c adrenergic receptors and the risk of CHF

Question 18

A2c decreased function =
B1 increased function =

Answer 18

A2c = increased Ne at synapse
B1 = increased response in cardiomyocytes

Question 19

what is the gene gene interaction between β1-Arg389 + α2c-Del322-325

Answer 19

polymorphisms synergistically increased risk of CHF only in black patients

b mutation alone = no change
a mutation alone = slight change