Pharmacogenomics Flashcards
What are the black box drugs:
black box warnings highlight serious and sometimes life-threatening adverse drug reactions within the labeling of prescription drug products
What are the common black box drugs (5)
Abacavir
Carbamazepine
Clopidigrel
Codeine
Rasburicase
Why do different people respond differently to the same dose of the same drug?
Genetic polymorphism
Describe the first pharmacodynamic study.
What was the conclusion?
Taste blindness
3/4 of the population. Can taste PTC
1/4 cannot
Autosomal recessive
Receptor- Ligand interactions differ on a hereditary basis
What are the 5 basic categories of genetic variation?
- variations that affect pharmacokinetics,
Enzymes that metabolize drugs
Transporters the move drugs (rare) - receptor variations CYP450
- Variability that leads to adverse reactions G6PD
- Variation in pathogenesis/ progression
- cancer pharmacogenetics
What are the most common bio markers that appear on drugs?
CYPs
G6PD
CYP2D6
Metabolizes 25% of drugs
Highly polymorphic
Can reduce or boost metabolism
What phenotypes does CYP2D6 give rise to?
Poor
Intermediate
Extensive
Ultra rapid
What is the relationship between CYP2D6 and Codeine?
Codeine is a prodrug converted into morphine by CYP2D6
Poor metabolizers get no effect.
Rapid metabolizers can activate codeine quickly risking morphine intoxication coma and death.
Black box
CYP2C19
Metabolized 10% of drugs
Highly polymorphic
What metabolic phenotypes does CYP2C19 give rise to?
Poor
Intermediate
Extensive
Ultra-Rapid
Poor (Asians)
What is the relationship between Clopidogrel and CYP2C19?
Clopidogrel is a prodrug activated by CYP2C19.
Clopidogrel is an anti platelet drug.
Poor metabolizers don’t activate Clopidogrel
CYP2C19 oxidizes Clopidogrel thenits hydrolyzed
What is the alternative to Clopidogrel?
Prasugrel also a prodrug does not rely on CYP2C19
What is the significance of UGT1A1?
It’s a phase 2 enzyme that glucaronizes billirubin.
Glucaronization increases solubility for excretion.
What does the homozygous polymorphism in UGT1A1 lead to?
Mild jaundice in 25% of Europeans.
Gilbert’s syndrome.