Pharmacogenetics webinars

Question 1

Pharmacogenetics principle

Answer 1

Gene variations that cause differences in drug action at level of absorption/excretion, liver metabolism, CNS receptor interactions, kidney function.

Question 2

Types of metabolisers

Answer 2

Poor metaboliser (PM): two defect genes
Intermediate (IM): one defect gene or two less active genes
Extensive (EM): two normal genes
Ultrarapid metaboliser (UM): gene duplication on one allele (CNV)

Question 3

Types of responders

Answer 3

1. normal responders
2. patients with adverse reactions or lack of response
   (due to: speed of metabolism, inappropriate interaction with targetformation of toxic metabolites, immune-mediated inverse reactions)

Question 4

Major pharmacogenomic biomarkers

Answer 4

Variations in genes important for drug response/adverser reactions.

1. HLA alleles
2. Drug metabolising enzymes
3. Drug transporters
4. Drug targets
5. Somatic genome (eg tumor mutations)

> > pharmacogenomic labels

Question 5

Ex for inter-individual drug responses

Answer 5

Anticoagulant warfarin
Lipid lowering statins
Anticlotting drug clopidogral
Codeine
Antiepileptic drug carbamazepine

Question 6

Clopidogrel metabolism

Answer 6

Prodrug (platelet inhibition). Bioactivation by CYP2C19. Decreased efficacy in slow metabolisers.
CYP2C19 inhibition by other drugs possible (eg proton-pump inhibitors)

Question 7

Codeine metabolism

Answer 7

Converted to morphine by CAP2D6.
Enters breast milk > side effect in infants.
(Mother is UM > high morphine levels, lethal for child)