Pharmacogenomics Flashcards
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
VKORC1 polymorphism (G1639A)
lower levels of VKORC1
this implies we need less warfarin in the system since there is less enzyme to be inhibited
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
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
Which are pro drugs?
Warfarin, Codeine, Clopidogrel, Tamoxifen, Vemurafenib?
Codeine
Clopidogrel
Tamoxifen
G6DP deficiency
hemolysis
it normally protects agains ROS -> deficiancy = early RBC death
BChE heredity
autosomal recessive
CYP2D6 and tamoxifen
deficiency = less active metabolite
active metabolites = more affinity at the estrogen receptor
(breast cancer drug)
BChE deficiency
slow break down of Succs → longer apnea time
warfarin and vit K Epoxide Reductase
Epoxide Reductase is the enzyme targeted by warfarin
coumadin inhibits it → less clotting happening
What metabolizes Codeine?
CYP2D6
what metabolizes Clopidogrel
CYP2C19
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
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)
cons of pharmacogenomics
- genetics is only a small piece of the big picture
- false positives
- cost
- it’s expensive
- benefits a minority of ppl
- sometimes more costly than dealing with adverse drug reactions
- delayed results and treatment
- when someone is sick they want immediate results
vemurafenib
targets a mutation in a specific proto-oncogene (BRAF) type - the V600E type
what metabolized Tamoxifen?
CYP2D6
NAT2 deficiency - effects
Isonizaid is not metabolized and pt’s suffer from toxicity to the drug (neuropathy etc)
NAT2 deficiency - general picture
acetylation polymorphism
not a SNP cause it has 2-3 point mutations
CYP2D6 and codeine metabolism
turns Codeine into morphine
low metabolizers = no effects; no pain relief
high metabolizers = morphine intoxication, respiratory depression
CYP2C19 polymorphism
- *1 = normal metabolism of clopidogrel = there will be active metabolites to inhibit ADP on platelets
- *2 = no metabolism of clopidogrel = no active metabolite to do the work
- most common
- *3 = no metabolism
- less common
- *17 = fast metabolism
pros of pharmacogenomics
- increases efficiency
- reduces toxicity
- reduces hospitalizations related to adverse drug reactions
- gemone sequence is a one in a life time test that allows for personalized care for the rest of one’s life
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
Who metabolized Warfarin?
CYP2C9
metabolizes S-warfarin; X5 more potent than R-warfarin
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.
