Drug Metabolism and Excretion Flashcards
What is drug elimination?
the irreversible removal of drug from body
Where does drug metabolism mainly occur?
in the liver
Where does the excretion of an unchanged drug occur?
many kidney (polar) but may be cleared by expiration for volatile materials or through the got
How does metabolism usually occur?
-two phases
-MODIFACTION: involves a cytochrome P450 dependent mixed function oxidase which causes oxidation, reduction or hydrolysis creating highly reactive compounds
-CONJUGATION
joins phase 1 metabolite onto another molecule in order to make it charged which labels it for excretion
What groups can be added on during conjugation?
-glutathione
-sulfate
-glycine
glucuronic acid
Why can the effective of dosing still continue even if a drug is no longer present?
-metabolites can still be active
What are the routed for drug and metabolite excretion?
- renal (particularly by filtration in the glomerulus)
- hepatic/biliary and hence faecal or enterohepatic elimination
- others: sweat, milk, breath
How does drug elimination in the kidney occur?
- 20% of plasma is filtered in glomerulus, charged or polar molecules tend to be trapped in tubules so lost in urine
- some drugs actively secreted into tubules (acid transporters (penicillin) and organic base transporters
- if drugs are secreted in the same transporter they can compete and hence slow their excretion
what is the equation for the clearance of drugs?
dC/dt = -kC^n
C=conc in compartment
k= constant
n= order of elimination of metabolism
What is the equation for C?
C= Cmaxe^-kt
What is the half life of a drug?
time taken for a drug concentration to half its initial value
What is zeroth order?
high drug concentration administered. Enzymes are saturated so are working at maximum rate regardless of conc of drug
concs falls linearly
