Pharmacogenetics + Pharmacogenomics Flashcards
What is pharmacogenetics?
The study of the genetic basis for the difference between individuals in response to drugs.
What is pharmacogenomics?
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
What is stratified medicine?
Selecting therapies for groups of patients with shared biological characteristics
tailored med
what are some factors for a drug being ineffective in px?
partly due to genetics but also,
environmental
age
lower water content
kidneys
liver
other drugs
…
for the personalised med model, what is the desired quarter of population outcome?
minimal tox
with max success
for px with: excessive tox + success
or minimal tox + failure od drug, what change may be done to their med?
treat with alt drug OR dose
if a subset of popn on drug experiences excessive tox and failure efficacy, what is done?
treat w alt drug
How is stratified medicine broken down? 3
Genetics of disease
Effect on treatment
Companion diagnostics
what are the major CYP enz involved in metabolism that inc/dec it?
cyp2D6
cyp3A4?
everyone has diff levels of CYP enzymes, related to racial group but moreso…
your personal genetic makeup,
so optimal dose varies for every px
severe SEs of warfarin?
Severe bleeding
Red or brown urine
Black or bloody stool
Vomiting of blood
SEs of NSAIDs
acute renal failure
GI bleeding
SE of ACEi
angiodema
SEs of aspirin
GI bleeds, angiodema
SEs of insulin + antidiabetic meds
hypoglycaemia
Why is the pharmacology of warfarin different in different people?
There are two isotopes: R and S, of warfarin that are metabolised by different CYP enzymes.
what enzymes have key role in warfarin pharmacology?
CYP 2C9
VKOR
vitamin K reductase
why is prescribing codeine in a CYP2D6 extensive metaboliser dangerous?
convert codeine to morphine very efficiently, morphine toxicity, respiratory depression and death.
toxic metabolite of morphine
morphine-6-glucoronide
binds to opioid receptor and is analgesic
How is genetic testing useful before prescribing warfarin?
Can determine warfarin sensitivity
What is abacavir?
Nucleoside analogue reverse transcriptase inhibitor
NRTI
How does hypersensitivity to abacavir present?
Fever
Malaise
Nausea
Diarrhoea
Skin rash
Death
What is abacavir toxicity attributed to?
HLA-B*57:01 allele
- screen px before use!
What is the HLA-B*57:01 allele responsible for?
= short arm of chromosome 6
Immune mediated adverse drug reactions
How does hypersensitivity to carbamazepine present?
Severe blistering and a rash
liver involvement
systemic w eosinophilia
What ethnicities are at risk of carbamazepine hypersensitivity?
Caucasian
Japanese
Chinese - HLA-B1502
What would you recommend to a patient that has reported a new rash after starting carbamazepine treatment?
Stop therapy immediately.
potentially life threatening
4 main areas that DNA collection kits cover?
traits: eye colour, lac intolerance…
inherited conditions: CF
drug response: genes linked
genetic risk factors
