Pharmacogenomics Flashcards
What is pharmacogenomics
The study of how genetic differences between patients account for differences in their responses to a drug
What are most variations due to
Single nucleotide polymorphisms
What is an allele
variant of a gene
1 allele from each parent which can be homozygous or heterozygous
What does CYP450 do
metabolises drugs and either activates of inactivates them
What are 3 types of metabolisers
- poor metabolizers
- intermediate metabolizers
- extensive metabolizers
- ultra rapid metabolisers
Why is pharmacogenomics important
to reduce the number of ADR so the right dose is selected for the right patient
What other factors affect ADRs
- age
- other drugs
- food intake
- environment
What are 5 benefits of personalised prescribing
- increase efficacy
- decrease toxicity
- increase compliance
- dose guidance - this depends on the extensiveness of the metaboliser
- efficient choice of medication and dose rather than trial and error
What type of drug is abacavir (HLA-B*57:01) and what disease is it used for?
antiretroviral used for HIV - it inhibits HIV replication
nucleoside reverse transcriptase inhibitor
What allele is abacavir hypersensitivity syndrome associated with?
HLA-B*57:01
If a patient is screened for HIV, what else do they need to be screened for?
HLA-B*57:01 allele
What is carbamazepine used for
- epilepsy
- bipolar affective disorder
- trigeminal neuralgia
Carbamazepine can induce Steven Johnson syndrome and toxic epidermal necrolysis, what allele causes this
HLA-B*15:02
What allele associated with carbamazepine is highly prevalent in southeast asia
HLA-B*15:02
Other than carbamazepine, Which other drugs had HLA-B*15:02 been linked to STS-TEN
- oxcarbazepine
- phenytoin
In northern Europe, which allele has been associated with hypersensitivity reactions such a maculopapular rash
HLA-A*31:01
What are Fluoropyrimidines
antimetabolite chemotherapy drugs for specific cancers
What cancers do Fluoropyrimidines treat
- gastrointestinal
- breast
- head and neck
What type of drug is 5-FU, is it inactive or active?
Fluoropyrimidine
What type of drug is Capecitabine and Tegafur
pro drugs
fluoropyrimidines
inactive, they are converted into the active form 5-FU
What serious adverse reactions occur with fluoropyrimidines
gastrointestinal
What enzyme activates 5-FU
DPD
What is the gene that encodes for the DPD enzyme
DPYD
Patient X is a poor metaboliser of DPD, if they are given a fluoropyrimidine for breast cancer, what could happen
Drug toxicity - can’t metabolise the drug and clear it
5-FU related ADR (gastrointestinal)
