Pharmacogenetics

Question 0

Other drugs with differences in metabolism

Answer 0

Metoprolol-> enhanced actions in poor metabolism
Codeine-> requires metabolic conversion and so reduced response in poor metabolisers
Tamoxifen-> poor metabolisers impaired conversion to active form

Question 1

CYP2D6

Answer 1

Genetic polymorphism
Poor metabolism of debrisoquine-> homozygous for recessive genes> 1-3%
Extensive metabolisers-> wild type
Ultra rapid metabolisers-> multiple copies of CYPD6 gene

Question 2

CYP2C9

Answer 2

Effects warfarin metabolism
Dose is individual to patients
Polymorphism
Genetic variation in metabolism of S enantiomer-> reduced clearance-> lower dose required

Question 3

VKORC1

Answer 3

Vit k epoxied reductive complex 1
Different halo types-> different warfarin requirements
-> warfarin resistance

Question 4

Dietary effects

Answer 4

Vit K rich foods -> Brussels sprouts-> reduce effects of warfarin

Question 5

Aspirin resistance

Answer 5

1/4 patients resistance to aspirin
Also at risk of increased CVD
Other anticoagulants don’t replace aspirin

Question 6

Clopidogrel

Answer 6

Needs to be oxidised by cytochromes and hydrolyse by PON1 esterases to thiol metabolite to work
-> pharmocological activity influenced by its bio transformation -> is a prodrug
Influenced by genotype
PQN1 Q192R polymorphism-> increased risk of thrombosis on a stent

Question 7

Altered pharmacological response

Answer 7

Polymorphisms in drug targets
B2 adrenoceptors in asthma
Drugs work less well over time