Pharmacogenetics Flashcards
What is pharmacogenetics?
Understanding how diff genotypes relate to diff drugs
= knowledge of which drugs will be safe/effective for each pt
What are the risk factors for drug inefficacy or toxicity?
Drug-drug interactions
Age
Renal/liver function
Lifestyle – smoking, alcohol
Genetic variation
Outline how genetic variation affects drug efficacy and toxicity
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
Give an example of the simple two allele genetic model explaining variability in drug efficacy/toxicity
Efficacy = normal (A) vs abnormal receptor (a)
Toxicity = normal (B) vs impaired metabolism (b)
AB, Ab, aB, ab
Give examples of Type ‘A’ and Type ‘B’ ADRs
A = common/predictable - diarrhoea from ABX
B = rare/unpredictable - liver disease/death from fluticasone
Outline the importance of genetic polymorphism affecting PKs and PDs
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