Personalised Medicines Flashcards
(17 cards)
Pharmacogenetics (PG)
Study of genetic variations that influence an individual’s response to drugs
Pharmacodynamic PG
How genetic variants in drug targets or their pathways e.g. receptors, enzymes, ion channels may change how a person responds to a drug
Pharmacokinetic PG
How genetic variants e.g. CYP450 enzymes affects the drug’s ADME
Ultra-rapid Metaboliser (UM)
Extra active enzyme
Low active drug = may need higher doses
High active metabolite = avoid pro-drugs
Extensive Metaboliser (EM)
Normal enzyme activity
Standard dose
Intermediate Metabolisers (IM)
Reduced enzyme activity
Higher drug levels = reduced dose / monitor for toxicity
Poor Metabolisers (PM)
Great reduction or no enzyme activity
Very high drug levels = lower the dose / use alternatives
No activation if pro-drug = avoid / use alternatives
Codeine: PK-PG
Metabolised to Morphine by CYP2D6
PM - low levels of enzyme. Two non-functional alleles of CYP2D6
UM - high levels of enzyme. At least two functional alleles of CYP2D6
Codeine: PK-PG effects
PM - Codeine won’t be activated resulting to accumulation of codeine
UM - high levels of Codein resulting to high risk of toxicity e.g. respiratory depression, overdose
Codeine recommendations
Not recommended on breastfeeding mothers and children
Mum - accumulation of codeine
Baby - risk of toxicity
Mercaptopurine: PK-PG
Thiopurine S-methyltransferase (TPMT) - metabolises / breaks down Mercaptopurine
Mercaptopurine: PK-PG
TPMT high enzyme levels = reduced efficacy due to being inactivated quickly - may need higher dose
TPMT low enzyme levels (PM) = accumulation of drug resulting to toxicity - reduce or alternatives
TPMT deficiency - decrease dose due to risk of subtherapeutic effect
Abacavir: PD-PG
Present HLA-B5701 allele - patient can’t tolerate
Absent HLA-B5701 allele - patient can tolerate
Phenytoin: PD-PG
Present HLA-B1502 allele - high risk for Stevens-Johnson Syndrome-TEN
Absent HLA-B1502 allele - low risk for Stevens-Johnson Syndrome-TEN
Warfarin: VKORC1
VKORC1 - encodes enzyme for recycling Vit. K to its active form which is needed to activate clotting factors. Affects how sensitive a patient is to Warfarin
VKORC1 inhibited by Warfarin = less Vit. K = less clotting factors = Anticoagulation
VKORC1 mutation = less enzyme for Warfarin to inhibit = lower dose
Warfarin: CYP2C9
CYP2C9 - metabolises Warfarin directly affecting the duration of Warfarin in the body
Rapid metaboliser = low Warfarin levels = low INR = higher dose
Poor metaboliser = high Warfarin levels = high INR = lower dose
Warfarin: CYP452
CYP452 - breaks down active Vit. K resulting to reduced clotting
CYP452 mutation = low enzyme activity = more Vit.K = higher dose
