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Flashcards in Pharmacogenomics Deck (20):
1

Pharmacokinetic variation drugs

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

2

N-acetyltransferase 2 Drugs and effects

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

3

Butyrylcholinesterase polymorphism drug and effect

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

4

Isoniazid adverse effect

neuropathy and hepatoxicity

5

Hydralazine and Procainamide adverse

Drug induced Lupus

6

Low NAT2

homozygous for autosomal recessive alleles

7

CYP2D6 drugs and effects

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

8

CYP2D6 adverse (codeine)

Poor-ineffective dose
Ultrarapid-overdose ->respiratory depression

9

CYP2D6 other

Poor metabolizers are homozygous for AR alleles
Ultrarapid metabolizers have multiple copies *up to 13* of gene

10

Thiopurine S-methyl-transferase drugs and effect

6-Mercaptopurine and Azathioprine
Decreased TPMT activity -> patient's can be treated with 1/10 of standard dose

11

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

Myelosuppression with standard dose

12

Thiopurine S-methyl-transferase other

TPMT catalyzes S-methylation of anti-CA thiopurines

13

Pharmacodynamic variation

Variation in drug target
Epidermal growth factor receptor mutation (EGFR)

14

Epidermal growth factor receptor mutation (EGFR) drug and effect

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

15

EGFR mutation other

EGFR is overexpressed in NSCLC ->targeted therapy

16

Combined PK and PD

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

17

CYP2C9 drug and effect

Warfarin
Decreased metabolism of warfarin
Increased risk of hemorrhage

18

VKORC1 drug and effect
Vit K epoxide reductase gene

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

19

Idiosyncratic

G6PD deficiency (A-)

20

G6PD deficiency (A-) drug and effect

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)