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Question 1

Proton pump inhibitor (PPI) metabolized into…

Answer 1

○ 5-hydroxyomeprazole (major) by CYP2C19
INACTIVE FORM

○ Omeprazole sulfone (minor) by CYP3A
ACTIVE FORM

Question 2

genetic polymorphism

Answer 2

a variation in DNA sequence
-in >1% of pop, polymorphism
-in <1% of pop, mutation

types: SNP, deletion, copy number variant

Question 3

SNP Nomenclature: VKORC1 1173 C >T

Answer 3

First letters: gene

Numbers: nucleotide position

First letter: original nucleotide

Second letter: change (SNP)

Question 4

Alleles

Answer 4

Different versions (alternate sequences) of a gene at a particular location on a chromosome

Question 5

What is a genotype?

Answer 5

• Each person carries 2 alleles of each gene
• The set of 2 alleles is his/her genotype

Question 6

What is a phenotype?

Answer 6

• The characteristics (e.g. clinical presentation) of an individual, that result from his/her particular genotype
  -Hair color, height, eye color, weight

Question 7

What is a haplotype?

Answer 7

A set of alleles at multiple, neighboring positions that coexist on the same chromosome

One individual inherits two copies of a haplotype

Question 8

CYP2C19: Population Prevalence

Answer 8

Asian

(CYP2C192 = 30%)
(CYP2C193 = 5%)

Question 9

Omeprazole exposure (AUC) is ____ in CYP2C19 poor metabolizers versus homozygous extensive metabolizers (CYP2C91/1)

Answer 9

HIGHER
(also have highest pH = increase antibiotic concentrations and improve antibiotic bioavailability)

Question 10

What is the effect of CYP2C19 on H. pylori cure rates?

Answer 10

Meta-analyzes concluded omeprazole efficacy is dependent on CYP2C19 genotype

Question 11

CYP2C19 (A/H, GC, FE, PP)

Answer 11

Question 12

PK

Answer 12