pharmacogenetics from FMS III

Question 1

N acetyltransferase-2

Answer 1

Isoniazid

• slow and fast acetylators
• elevation of plasma isoniazid increases the excretion of B6–>peripheral neuropath
• give B6 (pyridoxine) supplementation

Question 2

Thiopurine S methyl transferase (TMPT)

Answer 2

6-MP, 6-thioguanine, Azathioprine

• low, intermediate, high phenotypes
• low TMPT activity–>increase levels of tiopurines and increase in BM suppression
• adjust by decreasing dose of thiopurines

Question 3

Alcohol dehydrogenase ADH

Answer 3

rapidly metabolizes alcohol to acetaldehyde

Question 4

aldehyde dehydrogenase ALDH

Answer 4

ALDH2 variant, can’t efficiently oxidize acetaldehyde

• flushing reaction
• disulfiram like effects after drinking alcohol

Question 5

CYP2D6

Answer 5

tamoxifen

• poor metabolizers, extensive metabolizers
• tamoxifen not converted to active metabolites, increased risk of recurrence of breast cancer

Question 6

CYP2C9

Answer 6

Warfarin

• warfarin not efficiently inactivated
• decrease warfarin dose

Question 7

warfarin receptor

Answer 7

• resistance to warfarin induced anticoagulation

- lower affinity receptor to warfarin, dose is gradually increased to 10-30x conventional dose