Exam 5

Question 1

Number 1 on website for Pharmacogenomics

Answer 1

CPIC

Question 2

Pathogens can exist as

Answer 2

Bacteria
Viruses
Fungi
Parasites

Question 3

When discussing the patient and antimicrobial agent, what else must be taken into consideration?

Answer 3

Pathogen

Question 4

Goals of Pharmacogenomics in ID

Answer 4

Ensure optimal dosing to achieve desired drug concentrations at the site of infection

Avoid drug toxicity due to supratherapeutic dosing

Question 5

HLA-B is responsible for

Answer 5

Presenting peptides to immune cells and plays a critical role in normal immune recognition of pathogens

Question 6

A variant allele, HLA-B*57:01 is associated with

Answer 6

Increased risk of hypersensitivity reaction to the anti-HIV drug ABACAVIR

*Abacavir is NOT recommended

Question 7

Guideline for Efavirenz is based on what P450 CYP?

Answer 7

CYP2B6

Question 8

Efavirenz - 2B6 -> 8-hydroxyefavirenz (inactive) -2B6-> 8,14 dihydroxyefavirenz (inactive)

Efavirenz -2B6-> 7-hydroxyefavirenz (inactive)

Answer 8

WITHOUT CYP2B6 or with CYP2B6 variant allele, Efavirenz will stay active

• With Variant CYP2B6 516 G>T
• Leads to increased EFV concentrations and CNS toxicity
• EFV dose reductions may benefit patients with 516 G>T

Question 9

Normal Efavirenz symptoms

Answer 9

CNS Toxicity which leads to
Poor Quality of Life
Decreased Adherence
Treatment Discontinuation

Symptoms begins within 1 to 2 days after initiation and may resolve within 2 to 4 weeks of continued therapy.

Question 10

Atazanavir INHIBITS

Answer 10

UGT1A1

Question 11

UGT1A1 28/28 is a significant risk factor for

Answer 11

Severe Hyperbilirubinemia among patients taking atazanavir

Question 12

Voriconazole is metabolized by

Answer 12

CYP2C19

Question 13

*17 in CYP2C19 represents poor metabolizer or ultrarapid?

Answer 13

Ultrarapid

Question 14

In Adults take Voriconazole and is a CYP2C19 ultrarapid, rapid, or poor metabolizer, should you consider an alternative agent?

Answer 14

Yes

Question 15

In Pediatrics taking Voriconazole and is a CYP2C19 Ultrarapid or poor metabolizer, should an alternative agent be considered?

Answer 15

Yes

Question 16

PPIs are METABOLIZED BY

Answer 16

CYP2C19

Question 17

Omeprazole/Esomeprazole is 90% CYP2C19 to

Answer 17

Inactive 5-hydroxy-omeprazole

Question 18

The mitochondrion contains its own circular dsDNA. mtDNA is solely present in ova, resulting in strict maternal inheritance. mtDNA contains 37 genes

• 13 protein-encoding genes involved in oxidative phosphorylation
• 24 genes involved in protein translation
• • 22 tRNA
• • 2 rRNA genes
• MT-RNR for 12S rRNA*

Answer 18

MT-RNR1 1555A>G producees a mitochondrial 12s rRNA that is structurally similar to bacterial rRNA

Question 19

MT-RNR1 1555A>G variant + Aminoglycoside Exposure

Answer 19

Irreversible Ototoxicity

= Decrease mitochondrial protein synthesis, ATP production in the cochlea, and apoptosis

Question 20

With warfarin

Answer 20

Balance risk of thrombosis vs bleeding

Question 21

S-Warfarin inhibits

Answer 21

VKORC1 and uses CYP2C9 to inactivate metabolites

Question 22

CYP2C9 affects PK or PD

Answer 22

PK, metabolism of S-warfarin

Question 23

VKORC1 affects PK or PD

Answer 23

PD, warfarin target

Question 24

VKORC1 -1693G>A polymorphism

Answer 24

GA = reduced warfarin dose

AA greatly reduced warfarin dose (more sensitive)

Question 25

85-90% of Clopidogrel is converted to inactive acid metabolite. What P450 Cytochrome is used to convert clopidogrel to an active form?

Answer 25

CYP2C19

Question 26

If Clopidogrel Biotransformation and Platelet Inhibition Decreases and the patient has Loss of Function of Alleles

Answer 26

Risk of CV Events Increase

Question 27

Although a study proved that ticagrelor/prasugrel is noninferior to Clopidogrel in terms of thrombotic events, the two medication does

Answer 27

Lower bleeding risk

Question 28

If a patient is genotyped as an Intermediate Metabolizer or Poor Metabolizer (has any variant gene), they should be treated how?

Answer 28

Prasugrel 10 mg QD or Ticagrelor 90 mg BID

Question 29

Adverse of Effects of Statins

Answer 29

Myalgia Myopathy Rhabomyolysis

Question 30

Simvistatin relies on ________ for uptake of activated simvastatin

Answer 30

SLCO1B1

Question 31

If there is an variant on SLCO1B1

Answer 31

the adverse effects are at an increase

Question 32

For a poor metabolizerof SLCO1B1

Answer 32

Consider an alternative agent (pravastatin, rosuvastatin, fluvastatin)

Question 33

A 62 year old female has STEMI treated with PCI and DES. Her CYP2C19 genotype is ordered and returns as *1/*2. Which therapy is best? A. Prasugrel 5 mg daily B. Clopidogrel 75 mg daily C. Ticagrelor 90 mg BID D. Clopidogrel 150 mg daily

Answer 33

C

Question 34

A 62 year old female has STEMI treated with PCI and DES. Her CYP2C19 genotype is ordered and returns as *1/*1. Which therapy is best? A. Clopidogrel 75 mg daily B. Prasugrel 5 mg daily C. Clopidogrel 150 mg daily D. Ticagrelor 90 mg BID

Answer 34

A