Lecture 12 - pharmacogenomics

Question 1

describe genetic differences and impact on drugs

Answer 1

genetic differences in the DNA of our genes can change our pharmacokinetics (how our body process a drug) and pharmacodynamics (how a drug affects our body)

Question 2

what is personalised or stratified medicine?

Answer 2

when we look at a patients DNA and determine how they will respond well to a drug treatment and avoid prescribing drugs that might provoke an adverse reaction or death

Question 3

what are adverse drugs reactions often mediated to changes by ?

Answer 3

cytochrome P450 metabolising enzymes

Human Leukocyte Antigen HLA profile: how the body distinguishes ‘self’ form ‘non-self’ and so may play a role in how drugs trigger inappropriate immune response

drug transporters - how the drug enters or remain within the cells

Question 4

Give examples of where pharmacogenomics is used in routine

Answer 4

1. Avoiding serious adverse effects associated with fluoropyrimidine chemotherapy of certain cancers
2. Avoiding abacavir hypersensitivity syndrome (AHS) in the treatment of HIV
   3.Avoiding carbamazepine adverse effects, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in treatment of epilepsy and bipolar disorder.
3. Testing patients for response to clopidogrel to avoid risk of stroke

Question 5

Which gene is tested before prescribing fluoropyrimidine chemotherapy like 5-FU?

Answer 5

The DPYD gene.

Question 6

What is the function of the enzyme DPD?

Answer 6

it breaks down 5-FU into tolerable less toxic metabolites.

Question 7

What happens in DPYD deficiency?

Answer 7

5-FU accumulates, leading to severe off-target toxicity.

Question 8

What is Abacavir used for?

Answer 8

abacavir is a nucleoside reveres transcriptase inhibitor used to stop HIV

Question 9

What syndrome can Abacavir cause in susceptible patients?

Answer 9

Abacavir Hypersensitivity Syndrome (AHS). HLA-B*57:01 allele is associated with AHS

Question 10

What is Carbamazepine used for?

Answer 10

treating epilepsy and bipolar disorder.

Question 11

Which HLA allele is linked to serious ADRs from carbamazepine in SE Asians?

Answer 11

A: HLA-A*15:02

Question 12

what does clopidogrel do and why is it considered a pro drug ?

Answer 12

Prevents blood clots by inhibiting platelets. It must be activated by the CYP2C19 enzyme

Question 13

What happens if someone has a poor-metabolizer CYP2C19 variant?

Answer 13

the drug is ineffective → risk of stroke remains.