Al-Mehdi: Drug Metabolism Flashcards
goal of phase 1 of liver detoxification
water solubility
drug activation
goal of phase 2 of liver detoxification
water solubility
drug inactivation
goal of phase 3 of liver detoxification
excretion into bile
therapeutic window of a drug is between what two thresholds
minimal effective concentration (MEC)
minimal toxic concentration (MTC)
grapefruit juice + simvastatin =
myopathy (toxicity)
St. John’s Wort + simvastatin =
drug ineffective (never reaches MEC)
CYP450s located where
smooth ER
what induces enzyme production
phenobarbitol
receptor for Rifampin that dimerizes and goes into nucleus and leads to CYP3A4 being produced and rifampin’s degradation
PXR
____ activated by CYP2C19
Clopidogrel
inhibits CYP2C19
Omeprazole
omeprazole + clopidogrel=
platelet aggregation
cimetidine + omeprazole =
bleeding
_____inactivates CYP2C9
Cimetidine
warfarin + cimetidine =
bleeding
____ inhibits CYP3A4
Erythromycin (macrolide)
Erythromycin + Warfarin =
bleeding
Erythromycin + Ketoconazole
long QT + long QT = Torsades de Pointes
Rifampin + oral contraceptives =
baby
main reaction used in phase 2 of liver detoxification
Glucuronidation (UDP, UGT1A1) for drug inactivation (and drug conjugation)
what happens when glucuronidation happens w/ phenytoin +/or bilirubin
conjugation (water solubility)
active form of IRINOTECAN
SN-38
inactive form of IRINOTECAN
SN-38 + glucuronic acid (inactivated by UGT1A1)
mutation in OATP1B1/P1B3
Rotor syndrome
no reuptake of conjugated bilirubin