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Pharmacogenomics Flashcards

1
Q

What is pharmacogenomics

A

The study of how genetic differences between patients account for differences in their responses to a drug

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2
Q

What are most variations due to

A

Single nucleotide polymorphisms

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3
Q

What is an allele

A

variant of a gene
1 allele from each parent which can be homozygous or heterozygous

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4
Q

What does CYP450 do

A

metabolises drugs and either activates of inactivates them

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5
Q

What are 3 types of metabolisers

A
  • poor metabolizers
  • intermediate metabolizers
  • extensive metabolizers
  • ultra rapid metabolisers
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6
Q

Why is pharmacogenomics important

A

to reduce the number of ADR so the right dose is selected for the right patient

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7
Q

What other factors affect ADRs

A
  • age
  • other drugs
  • food intake
  • environment
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8
Q

What are 5 benefits of personalised prescribing

A
  • 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
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9
Q

What type of drug is abacavir (HLA-B*57:01) and what disease is it used for?

A

antiretroviral used for HIV - it inhibits HIV replication

nucleoside reverse transcriptase inhibitor

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10
Q

What allele is abacavir hypersensitivity syndrome associated with?

A

HLA-B*57:01

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11
Q

If a patient is screened for HIV, what else do they need to be screened for?

A

HLA-B*57:01 allele

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12
Q

What is carbamazepine used for

A
  • epilepsy
  • bipolar affective disorder
  • trigeminal neuralgia
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13
Q

Carbamazepine can induce Steven Johnson syndrome and toxic epidermal necrolysis, what allele causes this

A

HLA-B*15:02

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14
Q

What allele associated with carbamazepine is highly prevalent in southeast asia

A

HLA-B*15:02

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15
Q

Other than carbamazepine, Which other drugs had HLA-B*15:02 been linked to STS-TEN

A
  • oxcarbazepine
  • phenytoin
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16
Q

In northern Europe, which allele has been associated with hypersensitivity reactions such a maculopapular rash

A

HLA-A*31:01

17
Q

What are Fluoropyrimidines

A

antimetabolite chemotherapy drugs for specific cancers

18
Q

What cancers do Fluoropyrimidines treat

A
  • gastrointestinal
  • breast
  • head and neck
19
Q

What type of drug is 5-FU, is it inactive or active?

A

Fluoropyrimidine

20
Q

What type of drug is Capecitabine and Tegafur

A

pro drugs
fluoropyrimidines
inactive, they are converted into the active form 5-FU

21
Q

What serious adverse reactions occur with fluoropyrimidines

A

gastrointestinal

22
Q

What enzyme activates 5-FU

A

DPD

23
Q

What is the gene that encodes for the DPD enzyme

A

DPYD

24
Q

Patient X is a poor metaboliser of DPD, if they are given a fluoropyrimidine for breast cancer, what could happen

A

Drug toxicity - can’t metabolise the drug and clear it
5-FU related ADR (gastrointestinal)

25
Q

If someone has a head and neck cancer, breast cancer or gastrointestinal cancer and is being considered for fluoropyrimidine treatment, what must they be screened for

A

DPYD genetic variant

26
Q

What type of drug is gentamicin

A

aminoglycoside antibiotic

27
Q

What are common side effects of gentamicin

A

sensorineural hearing loss
renal failure (nephrotoxicity)

28
Q

What gene causes irreversible sensorineural hearing loss if given an aminoglycoside antibiotic

A

RNR1

29
Q

What 3 RNR1 variants can cause hearing loss

A
  • m.1555A>G
  • m.1095T>C
  • m.1494C>T
30
Q

What gene do newborns now get screened for before being given aminoglycoside antibiotics such a gentamicin

A

RNR1

31
Q

What type of drug is Codeine

A

analgesic drug for mild to moderate pain
antidiarrhoeal

32
Q

Codeine is a prodrug, what enzyme is it metabolised by

A

CYP2D6 to active morphine

33
Q

If you are a poor metaboliser of CYP2D6 will you experience analgesic effects

A

No as it is not converted into the active metabolite due to the genetic variance in CYP2D6 enzyme

33
Q

If you are a poor metabolizer of CYP2D6 will you experience analgesic effects

A

No as it is not converted into the active metabolite due to the genetic variance in CYP2D6 enzyme

34
Q

What type of drug is clopidogrel

A

Prodrug
antiplatelet drug for ACS, PCI, MI, AIS
P2Y12 receptor antagonist

35
Q

What enzyme converts inactive clopidogrel into its active metabolites

A

CYP2C19

36
Q

If you are a poor metabolizer of CYP2C19 will you experience antiplatelet effects

A

No as it is not converted into the active metabolite

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