IC4 PGx

Question 1

What 9 factors contribute to medication response?

Answer 1

1. Genomics
2. age
3. gender
4. weight
5. ethnicity
6. compliance
7. diet
8. concomitant drugs
9. concomitant diseases

Question 2

What are the main respective things that genetic factors change about PK and PD?

Answer 2

PK - enzyme activity (eg. cyp2C19)
PD - receptor activity (eg. SLC6A4)

Question 3

What are the 2 percentages to remember?

Answer 3

99% carry at least 1 clinically actionable PGx variant
24% of pts have been prescribed a drug for which they are predicted to have an atypical response

Question 4

What is a haplotype?

Answer 4

set of DNA variations inherited together on the same allele

Question 5

In allele nomenclature, what does *1 and *2 mean?

Answer 5

*1 = wild type, most abundant
*2 etc = chronological order in which variations were discovered

Question 6

What does phenoconversion mean?

Answer 6

Changing of phenotypes by external factors

Question 7

In displaying activity score, what number signifies normal (extensive) metabolism?

Answer 7

2.0

Question 8

What are the 4 main PGx resources?

Answer 8

CPIC
DPWG
PharmGKB
Sequence2script

Question 9

What are the 2 caveats of pharmacogenomics

Answer 9

1. genotyping vs sequencing
2. phenoconversion

Question 10

Explain what genotyping vs sequencing means

Answer 10

Genotyping assays identifies genomes as full sequencing assays are costly and generate a lot of data, which might miss out variations in non-genomic areas that may or may not be clinically significant

Question 11

Which resource allows to check if a variant is clinically significant?

Answer 11

PharmVar

Question 12

What is an example of phenoconversion in relation to taking an normal metaboliser taking a CYP2D6 strong inhibitor?

Answer 12

They will become a CYP2D6 poor metaboliser

Question 13

What is an example of phenoconversion in relation to taking an normal metaboliser taking a CYP2D6 moderate inhibitor?

Answer 13

The will become a CYP2D6 intermediate metaboliser

Question 14

What is the difference between clopidogrel and escitalopram and their interactions with a CYP2C19 poor metaboliser?

Answer 14

Clopidogrel is a prodrug metabolised by 2C19 to its active form so poor metabolisers = lower conc of active drug
Escitalopram is metabolised by 2C19 to be eliminated so poor metaboliser = higher conc of active drug, higher risk of SE and toxicity

Question 15

What are the 4 antidepressants that interact with 2D6?

Answer 15

paroxetine
venlafaxine
vortioxetine
fluvoxamine

Question 16

What is the recommendation for 2D6 ultra rapid metabolisers?

Answer 16

change paroxetine
increase venlafaxine and vortxetine

Question 17

What is the recommendation for 2D6 intermediate metabolisers?

Answer 17

decrease paroxetine

Question 18

What is the recommendation for 2D6 poor metabolisers?

Answer 18

decrease all 4
change v v f

Question 19

What are the2 antidepressants that interact with 2C19

Answer 19

Escitalopram
Sertraline

Question 20

What is the recommendation for 2C19 ultrarapid and rapid metabolisers?

Answer 20

change or increase escitalopram

Question 21

What is the recommendation for 2C19 intermediate metabolisers?

Answer 21

decrease escitalopram and sertraline

Question 22

What is the recommendation for 2C19 poor metabolisers?

Answer 22

change or decrease escitalopram and sertraline