Genetic Polymorphisms of Metabolic Reactions

gene duplication

increased enzyme activity

defective splicing

inactive enzyme

CYP2D6 alleles with reduced function

9,17,29,41

CYP2D6 alleles with no function

3,4,5,6

true or false poor metabolizers would have lower cmax than extensive metabolizer

false they would have a higher cmax

do poor metabolizers have long or short 1/2 life

long 1/2 life

what do you need to do to achieve therapeutic plasma conc of a drug for poor metabolizers

you need a lower dose

what do you need to do to achieve therapeutic plasma conc of a drug for ultra rapid metabolizers

you need a higher dose because the drug is removed so much faster

what percentage of the human genomes consists of exons

a. 1-2%

b. 25%

c. 75%

a. 1-2% protein coding genes are only a small percentage

true or false the human genome has some 300,000 genes

false we are not that different than other organisms

how many protein coding genes do humans have in their genome

20,000 our proteins are just more complex

How may a poor metabolizer of a prodrug be identified?

Would show sub-therapeutic effects, higher metabolic ratios, and more parent drug than the metabolite

How may a poor metabolizer of an active drug be identified?

Would show toxicity at standard doses

two broad classes of transporter proteins

ABC and OATP transporters

what transporter family only made up of efflux proteins

ABC transporters

what transporter family is made up of efflux or uptake transporters

SLC OATP transporters

What ABCB1 transporter alleles impact carbamazepine use outcomes?

Pts with the T allele of ABCB1 C345T require higher maintenance doses

What OATP1B1 transporter alleles impact repaglinide use outcomes?

521T>C is associated with higher repaglinide concentrations causing a more drastic decrease in BG

What metabolism phase II enzyme family does valproic acid inhibit?

UGTs

What metabolism phase I enzyme does clarithromycin inhibit?

CYP3A4