Lecture 4- principles of drug individualizing Flashcards
Drug metabolism
Define Gene
segment of DNA that contains information for encoding a protein
Define SNPs
single nucleotide polymorphism
Define alleles
different DNA sequences at a locus
Define genotypes
pair of alleles at a particular locus
Define phenotypes
the observable property of an organism; a trait such as height, weight, medical condition, etc.
Define Haplotype
a set of DNA variations, or polymorphisms, that tend to be inherited together
MDR1
for digosin (reduce dose if have MDR1 because have higher drug plasma level)
3 factors affecting patient drug response
- Environment: diet, lifestyle, socioeconomics, others
- Biology: age, sex, others
- Genetics
EM
normal metabolism (homozygous for the 2 “normal” alleles)
PM
poor metabolizer (homozygous w/two variant alleles)
IM
intermediate metabolizer (heterozygous)
UM
ultra-rapid metabolizer (gene duplication/multiplication)
systemic approach to genetic variations
identify genetic variation
determine who is impacted
identify how relevant to drug
determine how relevant to disease
goals of pharmacogenomics
4 rights
To Enhance drug efficacy and Reduce drug toxicity
Initial Dose
based on medical need and factors that will alter the PK or PD of drug (i.e. warfarin)
Phase I
oxidation
hydroxylation
reduction
hydrolysis
(P450 CYPs)
Phase II
conjugation:
- glucuronidation
- acetylation
- methylation
- glutathione conjugation
- sulphation
Maintenance Dose
adjust the maintenance dose by X% up or down based on INR: caution about factors that will alter the PK and PD of drug (i.e. warfarin)
Warfarin mechanism
Warfarin blocks VKOR enzyme that reduces Vit. K in order to coagulate.. therefore working as an anticoagulant
Irinotecan
UGT1A1*28
neutropenia (reduce neutrophil count?)
Codeine (prodrug for morphine)
CYP2D6 enzyme to activate it to morphine, but not actually morphine so no analgesic
PM: No analgesic effect
UM: respiratory depression
Clopidogrel (prodrug)
if CYP2C19 low then..
PM: No drug activity cause not activated