L8 Pharmacogenetics

Question 1

What is the difference between pharmacogenetics and pharmacogenomics

Answer 1

Pharmacogenomics deals with the entire genome (all the genes)

Question 2

Pick the gene that isn’t associated with isoniazid metabolism:

CYP2C9
CYP2E1
CYP3A4
GSTM1
NAT2

Answer 2

CYP 3A4 not associated

Major one is NAT2
2C9
2E1
GSTM1

All affect it

Question 3

What is your genotype for NAT2 if you are a slow acetylator (loss of function in NAT2)

Answer 3

(r,r) homozygous recessive

Question 4

What is the result of too rapid acetyaltion by NAT2

Answer 4

Hepatotoxicity

Question 5

What is the result of too slow acetylation by NAT2

Answer 5

Lupus

Question 6

What is the drug we use to test NAT2 activity?

Answer 6

ISONIAZID

Question 7

What is the genotype for rapid acetylators?

Answer 7

(R,r)

OR

(R,R)

Question 8

What is the 2nd most common metabolizing enzyme?

Answer 8

CYP 2D6

Question 9

How does 2D6 get mutated?

Answer 9

Deletions, duplication, or SNPs

Question 10

What enzyme metabolizes nortriptyline, codeine, and debrisoquin?

Answer 10

CYP 2D6

Question 11

What is the biggest ethnic group with no 2D6 enzymes activity?

Answer 11

Caucasian

Question 12

What is the biggest ethnic group with reduced 2D6 activity?

Answer 12

Japanese

Question 13

What is the test drug for 2D6?

Answer 13

Nortriptyline

Question 14

IF someone has no functional 2D6 genes, what will the levels of nortriptyline be compared to its metabolites?

Answer 14

High concentration of the drug

Low metabolites

Question 15

What is the OATP1B1 transporter?

Answer 15

Transfers stuff into hepatocytes

Question 16

What drugs are affected by OATP1B1 mutations

Answer 16

Statins

Question 17

What drug do you HAVE to do a genetic screening for before you put them on it?

Answer 17

Abacavir (AIDS drug)

Question 18

What gene is associated with having SJS as a reaction to abacavir?

Answer 18

HLA-B*5701

Question 19

What ethnicity has the most mutations in HLA 5701

Answer 19

Caucasians

No abacavir

Question 20

What is the difference between genotyping and phenotyping someone to see how they respond to drugs?

Answer 20

Genotyping: mapping out their genome. No need for probe drug

Phenotyping: using a probe drug to evaluate response

Question 21

What is the probe drug to test for serum cholinesterase?

Answer 21

Dibucaine

Question 22

What enzyme are we testing when we use debrisoquin as a probe drug?

Answer 22

CYP 2D6

Question 23

WHat is the most common form of gene mutations?

Answer 23

Nucleotide changes (SNP’s)