Pharmacogenomics 🧬

Question 1

Precautions when co- prescribing with TAMOXIFEN ?

Answer 1

Avoid co prescribing with CYP2D6 Inhibitors

Question 2

IRINOTECAN

side effects?

Answer 2

Myelosuppression, neutropenia, severe diarrhoea.

Question 3

IRINOTECAN

gene variants?

Answer 3

UGT*28 variant has an extra TA in regulatory region

*28 homozygotes =

• less SN-38 conjugation to SB-38G
  = GREATER RISK OF NEUTROPENIA

Question 4

Other an IRINOTECAN,

what other drugs are substrates for
UGT1A1*28 ?

Answer 4

1. Pazopanib
2. Belinostat

Question 5

Is 5-flurouracil (5-FU) a prodrug? If so, which enzyme is it metabolised by?

Answer 5

Yes, it is a prodrug.

Met in Liver by DPD

*DPD IS SUBJECT TO VARIANTS!

Question 6

Treatments (meds) based on tumour genetics ? 3

Answer 6

1. Trastuzumab = HER2 gene
2. Dafrafenib/ trametinib
   = BRAF V600E mutation
3. Gefitinib
   = EGFR mutations

Question 7

How does multi drug resistance work? 5

Answer 7

1. Increased efflux
2. Decreased influx
3. Activation if DNA repair
4. Blocked apoptosis
5. Activation of detoxifying systems (P450s)