Pgx Phase 1 - Study Guide

little/no enzyme activity, homozygotes for null alleles (* 1 / * 1)

Poor Metabolizers have:

reduced activity, heterozygotes for one deficient allele OR carry two reduced allele activity

INtermediate Metabolizers

normal activity, two normal alleles

Extensive metabolizers

elevated metabolism, multiple copies of gene

Ultra-rapid metabolizers 

Poor Metabolizers

Which metabolizer type is characterized by the following:

•  too slow drug metabolism, too high drug levels at ordinary doses, high risk of ADRs, no response from certain prodrugs

Ultra-rapid metabolizers

Which metabolizer type is characterized by the following?

• too rapid drug metabolism, no drug response at ordinary doses (nonresponders), if prodrug may need to decrease dose

Codeine

Which drug is activated by CYP2D6, no analgesic effect in Poor Metabs.; ADRs in Ultra Metabs. because prodrug! Can turn into Morphine!!!!

Tamoxifen

Which drug is  activated by CYP2D6, no clinical effect in Poor Metabs. 

• those with defective CYP2D6 alleles have increased risk of breast cancer relapse and lower survival rates

Clopidogrel

Which drug is activated by CYP2C19

• Intermediate and poor metabolizers experience reduced platelet inhibition and increased risk for cardiovascular AEs

SSRI’s, SNRI’s, and Atomoxetine

What drugs have CPIC guidance based on CYP2D6 or CYP2C19 genotypes?

• related to dose-related Sx from atomoxetine occur more frequently in CYP2D^ Poor Metabs.

HLA-A and HLA-B

What genes can increase carbamazepine toxicity/side effect?

HLA-B

What genes can increase Oxcarbazepine toxicity/side effect? Like Stevens Johnson syndrome?

CYP2C19

What enzyme allege/polymorphism can affect citalopram doses in the body? 

Functionalization; CYP450 which causes oxidation, reduction, hydrolysis)

Phase 1 drug metabolism

alleles (haplotypes) are typically numbered sequentially

• * → designates the allele 

• *1 → refers to wild type (most common form of the allele)

• Additional nucleotide changes are given by letters → CYP2D6*3A

• Extra gene copies (n) are denoted as → CYP2D6*3xn

Variant Nomenclature points

• Two copies of the same allele (homozygote) → CYP2C19*3/*3

• Two different alleles (heterozygote) → CYP2C19*1/*2

Additional Variant nomenclature points

• First block of letters and numbers identity the gene → CYP2C19

• #’s after indicate position of the affected nucleotide

• 1st letter = Wild Type

• 2nd letter = changed nucleotide

SNP Nomenclature

Ex: CYP2C19 681 G>A)