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Pharmacology > Pharmacogenomics > Flashcards

Flashcards in Pharmacogenomics Deck (20)
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1
Q

Pharmacokinetic variation drugs

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

N-acetyltransferase 2 Drugs and effects

A

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

3
Q

Butyrylcholinesterase polymorphism drug and effect

A

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

4
Q

Isoniazid adverse effect

A

neuropathy and hepatoxicity

5
Q

Hydralazine and Procainamide adverse

A

Drug induced Lupus

6
Q

Low NAT2

A

homozygous for autosomal recessive alleles

7
Q

CYP2D6 drugs and effects

A

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

8
Q

CYP2D6 adverse (codeine)

A

Poor-ineffective dose

Ultrarapid-overdose ->respiratory depression

9
Q

CYP2D6 other

A

Poor metabolizers are homozygous for AR alleles

Ultrarapid metabolizers have multiple copies up to 13 of gene

10
Q

Thiopurine S-methyl-transferase drugs and effect

A

6-Mercaptopurine and Azathioprine

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

11
Q

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

A

Myelosuppression with standard dose

12
Q

Thiopurine S-methyl-transferase other

A

TPMT catalyzes S-methylation of anti-CA thiopurines

13
Q

Pharmacodynamic variation

A

Variation in drug target

Epidermal growth factor receptor mutation (EGFR)

14
Q

Epidermal growth factor receptor mutation (EGFR) drug and effect

A

Gefitinib

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

15
Q

EGFR mutation other

A

EGFR is overexpressed in NSCLC ->targeted therapy

16
Q

Combined PK and PD

A

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

17
Q

CYP2C9 drug and effect

A

Warfarin
Decreased metabolism of warfarin
Increased risk of hemorrhage

18
Q

VKORC1 drug and effect

Vit K epoxide reductase gene

A

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

19
Q

Idiosyncratic

A

G6PD deficiency (A-)

20
Q

G6PD deficiency (A-) drug and effect

A

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)