In the clinic

Question 1

what are the four pharmacogenomic guidelines

Answer 1

CPIC – Clinical Pharmacogenetics Implementation Consortium
DPWG – Dutch Pharmacogenetics Working Group
Canadian Pharmacogenomics Network for Drug Safety (CPNDS)
French National Network of Pharmacogenetics (RNPGx)

Question 2

True or false - multiple agencies including FDA have drug labels which contains pharmacogenetic info

Answer 2

True

Question 3

How does SLCOB1 link to Simvastatin

Answer 3

SLCO1B1 facilitates the hepatic uptake of statins.
Decreased function of this transporter can markedly increase the systemic exposure to statins, the putative causal factor underlying the link to SAMS.

Question 4

how does ABCG2 link rosuvastatin

Answer 4

• ABCG2, which encodes the transporter ATP-Binding Cassette G2 is expressed in many different tissues including liver, blood-brain barrier and intestine.
• ABCG2 facilitates the export of compounds into the extracellular space.
• The common variant p.Q141K (c.421C>A, rs2231142); the minor A allele is associated with 30 to 40% reduced protein expression compared with the reference allele and with increased plasma levels of rosuvastatin.

Question 5

how does CYP2C9 linked to fluvastatin

Answer 5

• The CYP2C9 gene is highly polymorphic, with at least 71 variant alleles.
• The two most extensively studied variants are CYP2C92 (p.R144C; rs1799853) and CYP2C93 (p.I359L; rs1057910) which reduce CYP2C9 function by approximately 30-40% and 80%, respectively, and lead to increased systemic exposure to fluvastatin

Question 6

what hydrolyses R and S warfarin

Answer 6

R = CYP3A4, CYP1A2
S = CYP2C9

Question 7

which warfarin enantiomer is more biologically active

Answer 7

S

Question 8

Which VKORC1 polymorphisms effects warfarin doses

Answer 8

• G-1639A (upstream) and C1173T (intron 1) best studied
• G-1639A and C1173T form part of haplotype associated with lower warfarin dose
• A/A haplotypes have low levels of hepatic VKOR and vice verse for B/B

Question 9

what has been proven to improve warfarin treatment

Answer 9

genotyping

Question 10

what is the EU-pact

Answer 10

Randomised controlled clinical trial to investigate use of point of care genotyping to guide dosing of warfarin

Question 11

why is genotyping not always used in warfarin treatment despite EU-PACT

Answer 11

0.5-1% of people are prescribe warfarin
More newer DOAC drugs

Question 13

Abacavir is _ in patients with the HLA-B*5701 allele due to risk for abacavir _ reactions.

Answer 13

contraindicated
hypersensitivity

Question 14

what are some drugs which highlight the element of pharmacogentics in children

Answer 14

Ganaxolon, Risdiplam and Viltolarsen

Question 15

Eliglustat is used to treat _ as a _

Answer 15

Gaucher disease type 1
Glucosylceramide synthase inhibitor

Question 16

how does pharmacogenic effect eliglustat

Answer 16

drug metabolised mainly by CYP2D6
poor metabolisers at risk of cardiac arrythmia
requirement to genotype before prescribing