Pharmacogenomics (Exam 1)

Question 1

How can genetics affect someones drug response

Answer 1

Genteics can alter their response being hypoactive or hyperactive

Question 2

How does pharmacogenomics help people

Answer 2

it is personalized based on their specific genetic testing
help predict, explain, and treat

Question 3

How are doses adjusted based with genetics and without

Answer 3

Without genetics: give normal dose
With genetics: give normal, reduced, increased doses or use alternative therapy

Question 4

What are the 5 goals of personalized medicine

Answer 4

The RIght : Dose, Drug, Indication, Patient, Time

Question 5

What are unique facts about the Hman Genome

Answer 5

3.2 billion bases (6.4 billion total)
~30,000 genes 1-2% codes for proteins and 99% is the same between each individual person

Question 6

How many SNPs variants are there and how many cause an amino acid change

Answer 6

more than a million SNPs
60,000 cause an amino acid change

then AA change is different fro the wildtype

Question 7

What are Alleles

Answer 7

Alternate form of a gene that occur at the same locus (location on the chromosome)
can be somewhat common or rare

Question 8

What are the differences between SNPs (wild, synonymous, non-synonymous)

Answer 8

Wild type is the highest frequency
Synonymous (silent) change in base but no change in AA
Non-synonymous: change in base and change in AA resulting a change in the protein

Question 9

What are the effects on a prodrug and active drug if their are a poor metabolizer

Answer 9

Prodrug: poor efficacy and accumulation
Active: Good efficacy , accumulate, may need lower dose

Question 10

What are the effects on a prodrug and active drug if their are a ultra-rapid metabolizer

Answer 10

Prodrug: good efficacy and rapid effect
Active drug: poor efficacy, greater dose, or slow release

Question 11

What 2 populations does CYP2D6 affects and what general drugs does it metabolize

Answer 11

CYP2D6
- absent in 7% of caucasians
- hyperactive in 30% east africans
metabolizes: BB, antiarrhythmics, analgesics, antidepressant

Question 12

How does a poor metabolizer of CYP2D6 affect the metabolism of codeine

Answer 12

Codeine cannot be activated since it is a prodrug
CYP3A4 metabolizes codeine into an its inactive form

Question 13

What are purine analogs and what can do they treat, any side effects

Answer 13

Purines: adenine and guanine
purine analogs are incorporated into the DNA and stops it from forming/ replicating
Toxic side effects: immunosuppression
treatment for lymphoblastic leukemia, autoimmune disease, IBS, after translplant

Question 14

How is 6-mercaptopurine (6-MP) metabolized

Answer 14

Normally metabolized by TPMT to 6-methylmercaptopurine
Toxic pathways (metabolites): oxidized metabolites or 6-thioguanine nucleotides can destroy cells

Question 15

What are the effects of TPMT deficency and why do we want to run a test for it

Answer 15

TPMT deficiency is genetic disorder that can go undetected unless taking 6-MP. A deficiency could cause a conventional dose to be fatally toxic becasue they are poor metabolizers. This is why a test is needed.

Majority of people are fast metabolizers of 6-MP

Question 16

Why is warfarin dangerous

Answer 16

1 death for drugs causing adverse events

top drug associated with ER visits
frequency of major blleding 2-16%
minor bleeding events 29% /year

Question 17

How is warfarin metabolized and what can affect its metabolization

Answer 17

Metabolized by CYP2C9
It is a racemic mixture
(S) metabolized by CYP3C9
- 7-10x more potent
(R) metbolized by CYP2C19

Question 18

How can genetic testing be beneficial to taking warfarin

Answer 18

better dose prediction and reduced bleeding events
recommended but not required
only one copy of the variant allele have higher concentration of warfarin

Question 19

What is the traditional breast cancer assessment

Answer 19

biopsy: size, histologic type, tumir grade, lymph node staging, vascular or lymphatic invasion

Question 20

What receptors are found in breact cancer cells and how are they treated

Answer 20

60-70% express estrogen (ERs) and progesterone receptors (PRs)
TX: estrogen deprivation and tamoxifen or aromatase inhibitors

the receptors respond to estrogen.progesterone and proliferate the cell more

Question 21

What gene is amplified in breast cancer what drug does it respond to

Answer 21

HER 2
In 15-20% oc BCx, 2-20x amplification generating up to 100x normal receptor on cell surface
Tx: Herceptin

Normal cells have one copy of HER2 on each chromosome 17

Question 22

What is Herceptin (trastuzumab)

Answer 22

MAb and is very expensive
if not expressing HER2 not going to do anything
it binds to the receptor an shutsdown the signaling of the GF receptors and overall proliferation