Pharmacogenomics Flashcards Preview

Summer Pharm (2016) ** > Pharmacogenomics > Flashcards

Flashcards in Pharmacogenomics Deck (25):
1

What did the human genome project find?

>99% of nucleotide bases are the same in all humans

we have 3 billion bases

Note: the differences are mostly SNP variations

2

VKORC1 polymorphism (G1639A)

lower levels of VKORC1 

this implies we need less warfarin in the system since there is less enzyme to be inhibited

3

NAT2 - implication of having just protein coding region

having no introns, if something is wrong with this it will be more likely to cause a mutation cause there are no piece of it that are left out

4

coding region vs non-coding region

Coding region is more likely to cause a mutation, in the non coding region it is not expressed

Non-coding SNPs can change the way a gene is regulated or its stability

5

Which are pro drugs?

Warfarin, Codeine, Clopidogrel, Tamoxifen, Vemurafenib?

 

Codeine

Clopidogrel

Tamoxifen

6

G6DP deficiency

hemolysis

it normally protects agains ROS -> deficiancy = early RBC death

7

BChE heredity

autosomal recessive

8

CYP2D6 and tamoxifen

deficiency = less active metabolite

active metabolites = more affinity at the estrogen receptor 

(breast cancer drug)

9

BChE deficiency

slow break down of Succs → longer apnea time

10

warfarin and vit K Epoxide Reductase

Epoxide Reductase is the enzyme targeted by warfarin

coumadin inhibits it → less clotting happening

11

What metabolizes Codeine?

CYP2D6

12

what metabolizes Clopidogrel

CYP2C19

13

G6PD heredity

X- linked recessive pattern

male are more likely to be affected (only one X)

son of a dude with this deficiency could be just a carrier if the mom doesn't have the deficiency

14

VKORC1 - role?

Vit K Epoxide Reductase

reduces vit k (makes it in the form needed to catalyze the formation of the clotting factor 2, 7, 9, 10)

15

cons of pharmacogenomics

  1. genetics is only a small piece of the big picture
  2. false positives
  3. cost
    • it's expensive
    • benefits a minority of ppl
    • sometimes more costly than dealing with adverse drug reactions
  4. delayed results and treatment
    • when someone is sick they want immediate results

16

vemurafenib

targets a mutation in a specific proto-oncogene (BRAF) type - the V600E type

17

what metabolized Tamoxifen?

CYP2D6

18

NAT2 deficiency - effects

Isonizaid is not metabolized and pt's suffer from toxicity to the drug (neuropathy etc)

19

NAT2 deficiency - general picture

acetylation polymorphism 

not a SNP cause it has 2-3 point mutations

20

CYP2D6 and codeine metabolism

turns Codeine into morphine

low metabolizers = no effects; no pain relief

high metabolizers = morphine intoxication, respiratory depression

21

CYP2C19 polymorphism 

  1. *1 = normal metabolism of clopidogrel = there will be active metabolites to inhibit ADP on platelets
  2. *2 = no metabolism of clopidogrel = no active metabolite to do the work
    • most common
  3. *3 = no metabolism
    • less common
  4. *17 = fast metabolism

22

pros of pharmacogenomics

  1. increases efficiency
  2. reduces toxicity
  3. reduces hospitalizations related to adverse drug reactions
  4. gemone sequence is a one in a life time test that allows for personalized care for the rest of one's life

23

CYP2C9 and metabolism of __ drug

*1

*2

*3 

*1 (wild type) = normal metabolism of warfarin

*2 = 30% slower metabolism of warfarin

*3 = 90% slower

  • need the lowest dose

24

Who metabolized Warfarin?

CYP2C9

metabolizes S-warfarin; X5 more potent than R-warfarin

25

SNP is...

SNP is NOT ..

 

Single nucleotide polymorphism is a DNA sequence variation that occurs when a single nucleotide (A, T, C, or G) in the genome is altered

SNP is not the same as disease-causing mutation, and the majority of SNPs are in non-coding regions.