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WEEK 19:

Pharmacogenetics:

QuestionAnswer
pharmacogenetics genetic variations in that lead to changes in pharmacokinetics and pharmacodynamics of drugs between individuals across populations
why do patients fail to respond to treatment/ have adverse effect (2) metabolism (renal function, drug-drug interactions, and resistance) and pharmacogenetics (ethnicity),
polymorphisms ability to take many forms eg SNP (single nucleotide polymorphism) leading to mutation and amino acid substitution
example of SNP (single nucleotide polymorphism) sickle cell anaemia
P450 cytochromes make up a lot of enzymes involved in metabolism
CYP2D6 means cytochrome P450, family 2, subfamily D, polypeptide 6
classes of metabolisers poor (not metabolised), intermediate, extensive, and ultra-rapid
what does the class of metabolisers (eg poor) depend on variation of CYP2D6
warfarin oral anticoagulant metabolised by CYP2C9 polymorphism- acts a vitamin K antagonist where S-enantiomer reduces clearance so lower dose required
s warfarin mechanisms inhibits VKOR (VKOR converts vitamin K into y-glutamyl carboxylase which activates blood clotting factors)
vitamin K epoxide reductase complex 1 (VKORC1) gene encoding subunit 1 of VKOR
what happens when S warfarin is metabolised by CYP2C9 inactivates metabolites which reduces warfarin being broken down which decreases warfarin activity (more left in blood) so dose needs to be decreased
warfarin therapeutic window narrow
vitamin K rich foods do what reduce effectiveness of warfarin
aspirin resistance 1/4 patients are resistance and it is not related to COX- can lead to increased risk of CVD as it is an anti-platelet
clopidogrel anti-platelet and pro drug (inactive form) and first line treatment to overcome aspirin side effects
major determinant of clopidogrel efficacy paraoxonase-1 (PON1)
what happens to clopidogrel when it is metabolised by PON1 Q192R increases risk of thrombosis on stent
codeine -> morphine transformation catalysed by CYP2D6, giving it analgesia (inability to feel) and CNS-depressant effects
haplotypes combination of alleles/ set of SNPs found on same chromosome eg different haplotypes means different warfarin requirements
rosuvastatin prevalence and dose varies depending on racial groups
Created by: kablooey
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