Drug Interactions Flashcards
what causes changes in distribution
protein binding displacement reactions - usually low risk of being clinically relevant
also change due to modulation (inhibition/induction) of active transporters that alter distribution to a relevant tissue for efficacy or toxicity
what causes changes in elimination
excretion and metabolism interactions at enzymes and transporter levels
what is hepatic clearance
ratio between elimination rate by liver and incoming drug concentration
volume of blood entering the liver from which all the drug is removed per unit time
what does Eh mean
hepatic extraction ratio
range of Eh
from 0 (not eliminated) to 1 (completely eliminated)
high hepatic extraction ratio
if short time taken for the drug to leave blood cells, dissociate from plasma proteins, diffuse into hepatic membranes, be metabolised by enzymes, be transported to bile
what is the Eh for high extraction ratio
> 0.7
low hepatic extraction ratio
due to slow dissociation from RBC, slow dissociation from plasma protein, slow diffusion into hepatocytes, slow enzymatic reaction, slow transport into bile
what is the Eh for low hepatic extraction ratio
<0.3
what is Cl int
intrinsic clearance
the ability of the liver to eliminate the drug
what is Cl int dependent on
amount of enzyme present and the affinity of the drug for the enzyme
effects on Cl int
inducers increase Cl int
inhibitors decrease Cl int
low Eh effect on PK with inducer
increase Cl
decrease oral AUC
high Eh effect on PK with inducer
same Cl
decreased oral AUC
low Eh effect on PK with inhibitor
decreased Cl
increased oral AUC
