Pharmacogenomics

Question 1

Pharmacokinetic variation drugs

Answer 1

Variation in drug metabolizing enzymes
Butyrylcholinesterase aka pseudocholinesterase
N-acetyltransferase 2 (NAT2)
CYP2D6
Thiopurine S-methyl-trholine transferase

Question 2

N-acetyltransferase 2 Drugs and effects

Answer 2

Hydralazine & Procainamide, Isoniazid
Effect-slow acetylators have increased drug levels
Fast acetylators have decreased drug levels

Question 3

Butyrylcholinesterase polymorphism drug and effect

Answer 3

BCHE gener, Autosomal Recessive
Succinylcholine (depolarizing)
decreases the rate of metabolism resulting in prolonged paralysis
Dibucaine number >75 is normal

Question 4

Isoniazid adverse effect

Answer 4

neuropathy and hepatoxicity

Question 5

Hydralazine and Procainamide adverse

Answer 5

Drug induced Lupus

Question 6

Low NAT2

Answer 6

homozygous for autosomal recessive alleles

Question 7

CYP2D6 drugs and effects

Answer 7

Codeine (prodrug) and many others
Effect-
Poor metabolizers -> decreased codeine activation
Ultra rapid -> increased morphine effects
Most other drugs are activated by CYP2D6

Question 8

CYP2D6 adverse (codeine)

Answer 8

Poor-ineffective dose

Ultrarapid-overdose ->respiratory depression

Question 9

CYP2D6 other

Answer 9

Poor metabolizers are homozygous for AR alleles

Ultrarapid metabolizers have multiple copies up to 13 of gene

Question 10

Thiopurine S-methyl-transferase drugs and effect

Answer 10

6-Mercaptopurine and Azathioprine

Decreased TPMT activity -> patient’s can be treated with 1/10 of standard dose

Question 11

Thiopurine S-methyl-transferase adverse (6-Mercaptopurine and Azathioprine)

Answer 11

Myelosuppression with standard dose

Question 12

Thiopurine S-methyl-transferase other

Answer 12

TPMT catalyzes S-methylation of anti-CA thiopurines

Question 13

Pharmacodynamic variation

Answer 13

Variation in drug target

Epidermal growth factor receptor mutation (EGFR)

Question 14

Epidermal growth factor receptor mutation (EGFR) drug and effect

Answer 14

Gefitinib

ATP binding site mutation enhances drug effect (increases inhibition of tyrosine kinase)

Question 15

EGFR mutation other

Answer 15

EGFR is overexpressed in NSCLC ->targeted therapy

Question 16

Combined PK and PD

Answer 16

Multiple genes involved
CYP2C9
VKORC1 (Vit K epoxide reductase gene)

Question 17

CYP2C9 drug and effect

Answer 17

Warfarin
Decreased metabolism of warfarin
Increased risk of hemorrhage

Question 18

VKORC1 drug and effect

Vit K epoxide reductase gene

Answer 18

Warfarin
Dose can vary two fold depending on polymorphism
Hemorrhage and thrombosis adverse effect

Question 19

Idiosyncratic

Answer 19

G6PD deficiency (A-)

Question 20

G6PD deficiency (A-) drug and effect

Answer 20

Primaquine (sulfonamides and chloramphenicol)
90-95% decrease in G6PD function, decreased NADPH, decreased reduced glutathione, increase H2O2
Drugs or fava beans increase oxidative stress -> hemolytic anemia
Other-present in 10-20% of Africans and is though to be protective against malaria (exacerbated by antimalarials)