· Intro
· List of drugs
· Table: genotype, phenotype, frequency, effect
Nature |
· Microsomal enzyme |
Where |
· Liver > other |
Alleles |
· Two |
Function |
· Redox (especially O-demethylation) |
Importance |
· Affects 25% of clinically used drugs |
Problem |
· Polymorphism is common · Non-inducible |
Activated (prodrug) |
· Codeine -> morphine (↑↑potency) · Tramadol -> M1 (4 x analgesic efficacy, 200x MOP affinity) · Oxycodone -> oxymorphone (10-15x ↑potency) |
Inactivated |
· Methadone · SSRI · TCA · β-blocker · Clonidine |
Phenotype |
Genotype |
Frequency |
Ultrarapid |
>2 normal |
30% Nth Africa, Ethiopia, Arab 10% Greece, Portugal 1-3% others |
Normal |
2 normal |
80-90% |
Intermediate |
1 normal 1 reduced function |
2-10% |
Poor |
2 reduced function |
5-10% total 30% Hong Kong Chinese |
Drug activated |
· ↑Peak effect (~150%?), ↑toxicity · ↑Duration · High risk opioid toxicity: breastfeeding infant, sedated, sleep disordered breathing |
Drug inactivated |
· ↓Peak effect · ↓Duration |
Drug activated |
· ↓Peak effect · ↓Duration |
Drug inactivated |
· ±↑Peak effect, +/- ↑toxicity · ↑Duration |
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