7 - Pharmacogenetics and Pharmacovigilance

Question 1

what is pharmacovigilance ?

Answer 1

Identification, assessment and subsequent prevention of adverse drug reactions whilst optimising benefits

this will benefit patients well being, reduce overall ADR’s and save the NHS money in bed days ect

ensure drugs arent given that will cause SEVERE ADR’s and could lead to permanent damage, death, hospitalisation ect

ADR’s - are for a therapeutic drug given inside the therapeutic range

Question 2

what are the 2 broad types of ADR’s

Answer 2

type A - dose related
predictable (PK and PD)
common 
reversible 
dose adjustment
Bleeding - warfarin
Hypoglycaemia – diabetes
medication

type b- not dose related
unpredictable and uncommon
serious/irreversible
 need to stop treatment
Anaphylaxis – penicillin
Agranulocytosis – clozapine

Question 3

ADR can be split into 4 methods of action, they are…

give examples

Answer 3

Exaggerated response

Desired pharmacological effect at alternative/additional site (GTN – headache)

Additional/secondary pharmacological effect (QT length)

Triggering an immunological response (anaphylaxis)

Question 4

what is pharmacogenetics and pharmacogenomics

what is a solution to help with variability of pharmacogenetics

Answer 4

How individual gene may affect response to drug or drug response on body
• Pharmacogenomics – more broadly the whole genome and affects on drugs – considering epigenetics
• Understanding of phenotypic differences and how they affect therapeutics
• Population vs. individual
• Effective and or safe
• Further understanding and consideration of PG in combination with PV to reduce preventable ADRs

this also helps us understand why some people will not respond well/at all to certain therapeutic treatments
DUE to poss ADR’s it can be useful to screen/test for certain genes

EG - just read

Abacavir was associated with hypersensitivity in ~ 8 % patients treated for HIV – identified as a split antigen reaction screening for the split antigen resulted in 75 % reduction in reactivity

Cutaneous reaction (Stevens-Johnson syndrome or more severe toxic epidermal necrolysis) in patients taking carbamazepine – identified as a
reaction to another split antigen – predominantly found in Asian patients

Question 5

outline how antihypertensive treatment is related to PG

Answer 5

RAAS activity dictates this response

renin typically lower in African Caribbean populations so ACEi/ARB not primary choice for ↓BP (as poor response)
Angioedema more prevalent in African Caribbean populations than in young white Caucasians - worse side effects of ACEi

so for these patients we give CCB 1st instead - due to genetics

Question 6

otuline genetic polymorphism and how it can affect PK and PD

Answer 6

• Both PK and PD can be affected
- changes in PK and/or receptor structure, enzyme activity, immune response

eg- Aldehyde dehydrogenase deficiency – mutated ALDH2 – single aa change - East Asian and Northern European

this means tolerance to dose/drugs can vary wildly with individuals and populations