Pharmacogenomics

Question 1

Pharmacogenomics definition

Answer 1

variations in several genes (genome) that influence a drug’s response

Question 2

Warfarin metabolism (slide 15 no.1)

Answer 2

..

Question 3

NHS approach

Answer 3

NHS White/Board paper

Question 4

which genotypes are involved in alterations to warfarin metabolism?

Answer 4

CYP2C9, VKORC1

Question 5

Codeine metabolism

Answer 5

Codeine to morphine by CYP2D6

to norcodeine by 3A4

Question 6

What are recommendations for:

1. normal (extensive) metabolisers of codeine?
2. poor metabolisers
3. intermediate metabolisers
4. ultrarapid (increased formation of morphine)

Answer 6

1. use label recommendations
2. avoid codeine (lack of efficacy)
3. Use label, adjust if no response
4. avoid codeine due to potential for toxicity

Question 7

MHRA guidance for ultrarapid metabolisers?

Answer 7

codeine is contraindicated

Question 8

Clopidogrel metabolism

Answer 8

CYP2C19

Question 9

poor clopidogrel metaboliser risks

Answer 9

2-fold increase atherosclerosis
4-fold risk of stent thrombosis
20-40% of patients non or poor responders to clopidogrel

Question 10

Allele meaning for tamoxifen and dose recommendations

Answer 10

1. 2 inactive = poor metaboliser. Increase breast cancer risk
2. 1 active/inactive or variation = intermediate. Increased risk
3. 2 active = UM = no recommendation

Question 11

% patients with poor tamoxifen response

Answer 11

20-30% GENOTYPE STATUS NOT CONSIDERED IN DECISION MAKING

Question 12

how much could warfarin pharmacogenomic testing save in US?

Answer 12

1.1 billion dollars

Question 13

CYP variability

Answer 13

gene deletion - no enzyme - no metabolism

gene duplication - higher enzyme levels - increased metabolism of parent drug

Question 14

HLA-B*1502

Answer 14

Carbamazepine increased risk of SJS and TENS (Toxic Epidermal Necrolysis)

Question 15

HLA-B*5701

Answer 15

Abacavir sensitivity

Question 16

Type B ADRs and role of HLA

Answer 16

HLA variants trigger a T cell response triggering a sensitivity reaction