Pharmacogenetics

Question 1

What is pharmacogenetics?

Answer 1

Understanding how diff genotypes relate to diff drugs

= knowledge of which drugs will be safe/effective for each pt

Question 2

What are the risk factors for drug inefficacy or toxicity?

Answer 2

Drug-drug interactions

Age

Renal/liver function

Lifestyle – smoking, alcohol

Genetic variation

Question 3

Outline how genetic variation affects drug efficacy and toxicity

Answer 3

Young caucasian = high RAAS activity = ACEi/ARB will lower BP more effectively

Older afro-caribbean = lower RAAS activity = ACEi/ARB not as effective – thiazide diuretic or Ca channel blocker is first line therapy

Question 4

Give an example of the simple two allele genetic model explaining variability in drug efficacy/toxicity

Answer 4

Efficacy = normal (A) vs abnormal receptor (a)

Toxicity = normal (B) vs impaired metabolism (b)

AB, Ab, aB, ab

Question 5

Give examples of Type ‘A’ and Type ‘B’ ADRs

Answer 5

A = common/predictable - diarrhoea from ABX

B = rare/unpredictable - liver disease/death from fluticasone

Question 6

Outline the importance of genetic polymorphism affecting PKs and PDs

Answer 6

PK = ADME

PD = ion channels, receptors, enzymes, immune systems

E.g. CYP 2D6 = 6% of caucasians carrying 2 null alleles = no metabolism of drug, accumulation, re-routing