Personalised Medicine

Question 1

What is precision medicines?

Answer 1

an innovative approach to tailoring disease prevention and treatment that takes into account differences in people’s genes, environments, and lifestyles
- targeted therapies indicated for the treatment of human epidermal growth factor receptor 2–positive breast cancer

Question 2

What is the difference between pharmacokinetics and pharmacodynamics?

Answer 2

pharmacokinetics is the movement of drugs through the body, whereas pharmacodynamics is the body’s biological response to drugs

PK describes a drug’s ADME properties and PD describes how biological processes in the body respond to or are impacted by a drug (MOA, DOA).

Question 3

What are pharmacokinetics and pharmacodynamics in pharmacogenetics?

Answer 3

pharmacokinetic PG
- genetic variation in drug metabolisms and pathways

pharmacodynamic PG
- genetic variations in drug targets or their pathways

Question 4

How is codeine metabolised?
PK

Answer 4

codeine is inactive
- metabolised by CYP2D6 into active morphine
- morphine is 10x more potent than codeine

• metabolised by CYP3A4 into inactive norcodeine

Question 5

How are people classified into poor and ultra metabolisers of codeine?

Answer 5

poor metabolisers - have 2 non-functional alleles of CYP2D6 (gene that metabolises inactive codeine into active morphine)

ultra metabolisers - have at least 2 functional alleles of CYP2D6

Question 6

How is mercaptopurine metabolised?
PK

Answer 6

thiopurine S-methyltransferase (TPMT) metabolises mercaptopurine
- increased levels of TPMT results in reduced activity of mercaptopurine

Question 7

What is the meaning of subtherapeutic and supra therapeutic levels?

Answer 7

subtherapeutic - dose lower than that usually prescribed to treat a disease effectively

supra therapeutic - dose administered at levels greater than would normally be used in treatment of a medical condition

Question 8

How can the body react to abacavir?
PD

Answer 8

if individuals have HLA allele HLA-B*57:01 then they are prone to severe hypersensitivity reactions the given abacavir (NRTI)
- fever, vomtiing and arthralgia

people must undergo screening prior to treatment
- they cannot take abacavir if they have the HLA allele

Question 9

How can the body react to phenytoin?
PD

Answer 9

if individual have HLA allele HLA-B*15:02 then they can have severe subcutaneous adverse drug reactions
- stevens johnson syndrome

Question 10

What are the genes involved with warfarin?

Answer 10

CYP2C9 metabolises warfarin into its metabolites
- reduces activity of warfarin so more warfarin would be needed

warfarin blocks VKORC1
- reduces vitamin K activity

CYP4F2 breaks down active vitamin K into inactive hydroxy Vitamin K1
- means less warfarin is needed if CYP4F2 levels are higher

Question 11

What does it mean if a person is a carrier of XYZ allele?

Answer 11

carrier means they have fewer alleles of the gene named as it is heterozygous

carrier of VKORC1
- needs less warfarin

carrier of CYP2C9
- needs less warfarin
- if they are homozygous then they are normal metabolisers

carrier of CYP4F2
- needs more warfarin

Question 12

What is the function of VKORC1?

Answer 12

encodes for Vitamin K epoxide reductase protein
- is needed for clotting

Question 13

What are the barriers for pharmacogenetics?

Answer 13

Establishing Clinical validity
Education, guidelines, recommendations
Regulation
Cost and Reimbursement
Time needed for testing