Pharmacogenomics Flashcards
Pharmacogenetics
altered drug response in an individual linked to a genetic cause
Pharmacogenomics
altered drug response in a population linked to a genetic cause
Allele
alternative form of a gene
Genetics can cause what type of differences?
metabolism of the drug
alteration of the drug target
absorption of the drug
single nucleotide polymorphism (SNP)
alteration of 1 nucleotide
can cause altered function
SNP in coding region
changes the amino acid encoded
SNP in intron
alters the promotor/splicing
Variable number tandem repeats (VNTR)
repeating strings of nucleotides that can alter function
usually 4-40
True positive
has an alteration and identifies as alteration
true negative
has no alteration and identifies as no alteration
false positive
identifies as alteration when not
false negative
identifies as no alteration when is
what is the effect of a false positive in an efficacy study?
disease is untreated
what is the effect of a false negative in an efficacy study
think drug wont work but it would have
end up treating with different drug
what is the effect of a false positive in a safety study
think a complication will occur when it wont
What is the effect of a false negative in a safety study?
patient will have ADR
Abacavir
Nucleotide reverse transcriptase inhibitor
used in combo therapy for HIV
blocks reverse transcriptase by blocking elongation
4-8% of patients get hypersensitity reaction linked to HLA-B*5701; intense rash/fatality
Bupropion
treats depression; smoking cessation aid
acts as DAT and NET inhibitor and as an agonist at nicotinic receptors
non-tricyclic antidepressant
CYP2B6 responsible for metabolism
Warfarin
oral anticoagulant used to treat/prevent embolic/thrombotic events
non-competitive inhibitor of VKORC-1
universal dosing difficult
risk of bleeding
metabolized by CYP2C9
VKORC1 wild type mutation
5 mg
Normal resistance phenotype
VKORC-1 Mutation Ala41->Ser
16 mg
Moderate resistance phenotype
VKORC-1 Mutation Arg 48 -> Gly
34 mg
Major resistance phenotype
VKORC-1 Mutation Leu128 ->Arg
> 45 mg
severe resistance phenotype
CYP2CP*1
wild type
CYP2C9*2
Arg 144 -> Cys
70% enzymatic activity, functionally deficient
CYP2C9*3
Ile 359 -> Leu
5% enzymatic activity, severely deficient
Methylphenidate
treats ADHD
DAT and NET inhibitor; increased levels of dopamine in the synapse
VNTR of Dopamine D4
3’ intron repeat
people lacking a 10 repeat allele show increased drug response
VNTR of DAT
exon 3 repeat
people with 4 repeat allele show increased drug response
Mapping the human genome
completed in 2000
originally cost $2.7 billion and took 10 years
can now map for $1000 within a few days
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)
treatment involving gene editing
Cas9
bacterial endonuclease
Induced Pluripotent Stem Cells (iPS)
come from skin/blood
can turn skin cells back into stem cells
used to test drugs on an individual’s actual cells
