Precision Medicine and Pharmacogenomics

Question 1

CYP that metabolizes codeine, hydrocodone, oxycontin, and other opioids

Answer 1

CYP2D6

Question 2

Metabolism of 5-Fluorouracil

Answer 2

Most is degraded by DPD (dihydropyrimidine dehydrogenase) in liver

The rest goes to inhibit Thymidylate Synthase (pyrimidine synthesis pathway)

Mutations can occur at either DPD or TS

Question 3

CYP respobsible for metabolizing MDMA and polybrominated diphenylether (flame retardant)

Answer 3

CYP2B

Question 4

CYP inhibited by SSRI’s and Tamoxifen

Answer 4

CYP2D6

Question 5

Grapefruit Juice

Answer 5

Inhibits CYP3A4

Question 6

CYP inhibited by Grapefruit Juice and Cimetidine (H2 blocker)

Answer 6

CYP3A4

Question 7

DPD variants

Answer 7

Patients with low DPD activity cannot inactivate 5FU, leading to toxic side effects

Question 8

Deficiency leads to Primary congenital glaucoma

Answer 8

CYP1B1

Question 9

CYP that can be uncoupled

Answer 9

CYP2E1

Question 10

TS Variants

Answer 10

There is a polymorphic tandem repeat that can occur with the Thymidylate Synthase gene

Since the gene has higher activity, more drug will be required and patient is more resistant to therapy

Question 11

Examples of DNA Variants

Answer 11

1. Single Nucleotide Polymorphisms
2. Larger insertions or deletions
3. Chromosomal aberrations (like translocation)

Question 12

Major CYP in humans that metabolizes over 50% of common drugs

Answer 12

CYP3A4 / CYP3A5

Question 13

Trimethylaminuria

Answer 13

“Fish odor syndrome” caused by polymorphism in Flavin Monooxygenase FMO3

Question 14

CYP that metabolizes viagra and oral contraceptives

Answer 14

CYP3A4

Question 15

CYP that metabolizes Polycyclic Aromatic Hydrocarbons, Retinoic Acid, and Arachidonic Acid

Answer 15

CYP1B1

Question 16

What two enzymes are involved in Warfarin metabolism

Answer 16

CYP2C9 and VKORC1 (Vitamin K Reductase)

Question 17

Variants in Vitamin K metabolism?

Answer 17

A Allele for Vitamin K reductase produces less vitamin K

Question 18

Metformin Metabolism and Polymorphism

Answer 18

SLC47A1/MATE1 is the transporter responsible for excretion of Metformin into bile

669 Polymorphism associated with best outcomes (highest decrease in Hb A1c)

A alleles better than G alleles (A allele inactivates the transporter)

Question 19

Warfarin CYP Variants

Answer 19

CYP2C9 is the enzyme that metabolizes Warfarin

*1 is normal

*2 reduces metabolism by 30%

*3 reduces metabolism by 90%

Question 20

CYP induced by cigarette smoke and caffeine

Answer 20

CYP1A2

Question 21

CYP responsible for nicotine metabolism

Answer 21

CYP2A6 and CYP2A13

Question 22

Alixaban (Eliquis - Anticoagulant) CYP

Answer 22

CYP3A4

Question 23

CYP that metabolizes ethanol and small hydrocarbons

Answer 23

CYP2E1

Question 24

Roche AmpliChip

Answer 24

Microarray that tests for all known CYP variants

Outputs them in a form and tells you what drugs to avoid

Question 25

Clopidogrel (Plavix) CYPs

Answer 25

CYP2C19

*1 is normal

*2 and *3 are poor metabolizers

*17 is ultra-metabolizer

Question 26

Pharmacogenomics

Answer 26

Science of determining how genetic variability influences physiological response to drugs, from absorption and metabolism to pharmacologic action and therapeutic effect

Question 27

Hyrdocodone toxicity

Answer 27

Caused by rapid metabolizers of CYP2D6 variant

Question 28

CYP induced by Rifampicin and Phenobarbital

Answer 28

CYP3A4