Precision Medicine and Pharmacogenomics Flashcards Preview

Foundations of Disease and Therapy > Precision Medicine and Pharmacogenomics > Flashcards

Flashcards in Precision Medicine and Pharmacogenomics Deck (28):
1

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

CYP2D6

2

Metabolism of 5-Fluorouracil

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

3

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

CYP2B

4

CYP inhibited by SSRI's and Tamoxifen

CYP2D6

5

Grapefruit Juice

Inhibits CYP3A4

6

CYP inhibited by Grapefruit Juice and Cimetidine (H2 blocker)

CYP3A4

7

DPD variants

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

8

Deficiency leads to Primary congenital glaucoma

CYP1B1

9

CYP that can be uncoupled

CYP2E1

10

TS Variants

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 

11

Examples of DNA Variants

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

12

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

CYP3A4 / CYP3A5

13

Trimethylaminuria

"Fish odor syndrome" caused by polymorphism in Flavin Monooxygenase FMO3

14

CYP that metabolizes viagra and oral contraceptives

CYP3A4

15

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

 

CYP1B1

16

What two enzymes are involved in Warfarin metabolism

CYP2C9 and VKORC1 (Vitamin K Reductase)

17

Variants in Vitamin K metabolism?

A Allele for Vitamin K reductase produces less vitamin K

18

Metformin Metabolism and Polymorphism 

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)

19

Warfarin CYP Variants

CYP2C9 is the enzyme that metabolizes Warfarin

*1 is normal

*2 reduces metabolism by 30%

*3 reduces metabolism by 90%

20

CYP induced by cigarette smoke and caffeine 

CYP1A2

21

CYP responsible for nicotine metabolism

CYP2A6 and CYP2A13

22

Alixaban (Eliquis - Anticoagulant) CYP

CYP3A4

23

CYP that metabolizes ethanol and small hydrocarbons

CYP2E1

24

Roche AmpliChip

Microarray that tests for all known CYP variants

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

25

Clopidogrel (Plavix) CYPs

CYP2C19

*1 is normal

*2 and *3 are poor metabolizers

*17 is ultra-metabolizer

26

Pharmacogenomics

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

27

Hyrdocodone toxicity

Caused by rapid metabolizers of CYP2D6 variant 

28

CYP induced by Rifampicin and Phenobarbital

CYP3A4