Liver And Metabolic Drug Interactions Flashcards
How is hepatic clearance calculated
Hepatic blood flow X hepatic extraction ratio
What is the hepatic extraction ratio
Fraction of Cedric extracted from blood during single pass through the liver
What is the hepatic clearance dependent upon
Fraction of drug bound to albumin
Liver blood flow
Liver intrinsic clearance - metabolic enzyme activity
Where are oral drugs absorbed
GI tract and delivered via portal vein to liver
Where does metabolism mainly occur
In the liver
How many phase reactions occur during metabolism
3
Which phase is CYP P450 mediated?
Phase 1
Which reactions is in phase 1?
Oxidative reactions
Which hepatic CYP P450 is most significant?
CYP3A4
Which factors affect drug metabolism
Physio chemical factors = drug structures
Biological factors
Environment factors
What happens when there is competitive inhibition of phase 1 metabolic enzyme of CYP P450?
increased toxicity
Decreased efficacy
Why is grapefruit juice important for CYP3A4
It inhibits CYP 3A4
Increased plasma peak drug concentration of CCBs (for hypertension and angina) = not eliminated
Therefore CCBs (felodopine) aren’t metabolised and cannot be absorbed
Increased oral bioavailability of felodipine
