Pharmacogenetics

Question 1

CYP2C19

Answer 1

Phenytoin (anti seizure, poor metabolizers have too high concentration)

Omeprazole (PPI, low short term side effects, poor metabolizers are benefitted)

Clopidogrel (anti platelet aggregation, is a pro drug, poor metabolizers are getting too little drug)

Question 2

CYP2C9

Answer 2

Warfarin

Anti coagulant

*2 and *3 versions are slow and slower that normal variant *1

Question 3

VKORC1

Answer 3

Warfarin competitively blocks this. Some people express more VKORC1 and so they require more warfarin.

This only complicates things because the level of VKORC1 expression is genotypically separate from CYP2C9 normal metabolizers or *2 or *3 slow metabolizers.

There are no ultrafast CYP2C9 metabolizers

Question 4

Pseudocholine Esterase

Answer 4

Succinyl choline muscle relaxant

Slow metabolizers can’t breath or it takes hours to clear rather than minutes

Question 5

TPMT

Answer 5

Thiopurine methyl transferase tpmt
6-MP chemotherapy
TPMT inactivates 6-MP so slow metabolizers get over activation of 6-MP

Question 6

SLCO1B1

Answer 6

OAT1B1
Low expression C allele
Uptake of hydrophilic drugs decreased in liver
Status, side effects = myalgia
Low expression means too much statin = muscle destruction

Question 7

CYP2D6

Answer 7

Turns codeine into morphine
Slow CYP2D6 metabolizers get no morphine
Multiple CYP2D6 (ultrafast metabolizers) copies get too much morphine

Question 8

CYP3A

Answer 8

Grapefruit juice inhibits intestinal CYP3A and makes drug more bioavailable effectively increasing the amount of drug getting into your system