pharmacogenetics

Question 1

warfarin (oral anticoagulant) pharmacogenetics

Answer 1

dose is individual to patient CYP2C9 polymorphism (reduced activity).
genetic variation in metabolism of S-enantiomer:
reduced clearance
lower doses required

Question 2

VKOR

Answer 2

Activates Vitamin K= coagulation. Vitamin K epoxide reductase complex 1 (VKORC1) is the gene encoding subunit 1 of VKOR

Question 3

aspirin resistance

Answer 3

1/4 of patients resistant to aspirin.
not related to COX enzymes.
Also increased risk of CVD.
other anti-platelets do not substitute for aspirin.
Could be due to incomplete absorption from enteric aspirin.
bioavailability seems to play an important role.

Question 4

clopidogrel

Answer 4

paraoxonase-1 PON1 is a major determinant of clopidogrel efficacy by allowing for platelet inhibition.
it is a prodrug.
pharmacological activity is influenced by its biotransformation.
influenced by genotype.
PON1 Q192R polymorphism: increased risk of thrombosis on stent

Question 5

codeine/morphine

Answer 5

codeine only has mild opioid properties.

• most of its analgesia and CNS-depressant effects result from biotransformation to morphine
• this reaction is catalysed by CYP2D6
• poor metabolisers would show no response to the analgesic effects of codeine

Question 6

VKORC1

Answer 6

Vitamin K epoxide Reductase Complex 1
pharmacodynamic
VKOR= activates vit K= coagulation.
VKORC1 is the gene encoding subunit 1 of VKOR.
different haplotypes would mean different warfarin requirements.
haplotype can refer to a combination of alleles or to a set of single nucleotide polymorphisms (SNPs) found on the same chromosome

Question 7

pharmacodynamic

Answer 7

polymorphism in drug target e.g. receptors

Question 8

rosuvastatin

Answer 8

prevalence often varies between racial groups.
BNF: max dose 40mg (Caucasian), max dose 20mg (asian origin).
increased plasma concentrations achieved in patients of Asian origin~ metabolic/genetic differences yet to be determined.