Pharmacogenetics + Pharmacogenomics

Question 1

What is pharmacogenetics?

Answer 1

The study of the genetic basis for the difference between individuals in response to drugs.

Question 2

What is pharmacogenomics?

Answer 2

Use of population genetic information for drug research. design and development.
Clinical management of drug therapy - drug dosing and choice

• may be lots of genes having affect on drug rather than 1 single strong gene

Question 3

What is stratified medicine?

Answer 3

Selecting therapies for groups of patients with shared biological characteristics

tailored med

Question 4

what are some factors for a drug being ineffective in px?

Answer 4

partly due to genetics but also,
environmental
age
lower water content
kidneys
liver
other drugs
…

Question 5

for the personalised med model, what is the desired quarter of population outcome?

Answer 5

minimal tox
with max success

Question 6

for px with: excessive tox + success
or minimal tox + failure od drug, what change may be done to their med?

Answer 6

treat with alt drug OR dose

Question 7

if a subset of popn on drug experiences excessive tox and failure efficacy, what is done?

Answer 7

treat w alt drug

Question 8

How is stratified medicine broken down? 3

Answer 8

Genetics of disease
Effect on treatment
Companion diagnostics

Question 9

what are the major CYP enz involved in metabolism that inc/dec it?

Answer 9

cyp2D6
cyp3A4?

Question 10

everyone has diff levels of CYP enzymes, related to racial group but moreso…

Answer 10

your personal genetic makeup,
so optimal dose varies for every px

Question 11

severe SEs of warfarin?

Answer 11

Severe bleeding
Red or brown urine
Black or bloody stool
Vomiting of blood

Question 12

SEs of NSAIDs

Answer 12

acute renal failure
GI bleeding

Question 13

SE of ACEi

Answer 13

angiodema

Question 14

SEs of aspirin

Answer 14

GI bleeds, angiodema

Question 15

SEs of insulin + antidiabetic meds

Answer 15

hypoglycaemia

Question 16

Why is the pharmacology of warfarin different in different people?

Answer 16

There are two isotopes: R and S, of warfarin that are metabolised by different CYP enzymes.

Question 17

what enzymes have key role in warfarin pharmacology?

Answer 17

CYP 2C9
VKOR
vitamin K reductase

Question 18

why is prescribing codeine in a CYP2D6 extensive metaboliser dangerous?

Answer 18

convert codeine to morphine very efficiently, morphine toxicity, respiratory depression and death.

Question 19

toxic metabolite of morphine

Answer 19

morphine-6-glucoronide

binds to opioid receptor and is analgesic

Question 20

How is genetic testing useful before prescribing warfarin?

Answer 20

Can determine warfarin sensitivity

Question 21

What is abacavir?

Answer 21

Nucleoside analogue reverse transcriptase inhibitor
NRTI

Question 22

How does hypersensitivity to abacavir present?

Answer 22

Fever
Malaise
Nausea
Diarrhoea
Skin rash
Death

Question 23

What is abacavir toxicity attributed to?

Answer 23

HLA-B*57:01 allele

• screen px before use!

Question 24

What is the HLA-B*57:01 allele responsible for?

Answer 24

= short arm of chromosome 6

Immune mediated adverse drug reactions

Question 25

How does hypersensitivity to carbamazepine present?

Answer 25

Severe blistering and a rash
liver involvement
systemic w eosinophilia

Question 26

What ethnicities are at risk of carbamazepine hypersensitivity?

Answer 26

Caucasian
Japanese
Chinese - HLA-B1502

Question 27

What would you recommend to a patient that has reported a new rash after starting carbamazepine treatment?

Answer 27

Stop therapy immediately.
potentially life threatening

Question 28

4 main areas that DNA collection kits cover?

Answer 28

traits: eye colour, lac intolerance…
inherited conditions: CF
drug response: genes linked
genetic risk factors