drug elimination Flashcards
how is drug excreted?
in urine, faeces or bile
what does elimination a combination of?
metabolism & excretion
what is the primary organ of elimination?
kidneys
how is elimination completed in kidney?
renal filtration with blood plasma
->water & most electrolytes reabsorbed into blood circulation in renal tubes
->drug metabolites rendered polar (water soluble) by phase II metabolism are not reabsorbed thus excreted in urine
does absorption occur in vascular or non vascular ROA and what are examples of each?
vascular
= IV
= NO absorption (straight into systemic circulation)
non-vascular
= intramuscular, subcutaneously, oral, inhalation
= absorption phase (simultaneously absorbed & eliminated - mostly absorption in absorption phase)
what is clearance?
expression of the elimination of a drug from the body
- specifically = volume of blood removed (cleared) of drug per unit of time (L/hour)
- it’s a flow parameter -> doesn’t tell you how much of drug is removed
what elimination routes can clearance be broken down into?
renal clearance = CLR
haptic clearance = CLH
other routes = CLO
total clearance = CLT
why is clearance important?
helps us determine the dosage rate needed to maintain desired drug plasma concentration
what is 1st order kinetics?
rate of elimination proportional to drug plasma concentration -> good for drugs, it makes it easier to get steady state
what is 0 order kinetics?
when rate of elimination no longer dependant on plasma concentration
= problematic for drugs as it happens when reached Vmax (max rate of drug elimination) which means drug plasma concentration very high -> toxic effects
what is an example of a drug that is very problematic due to it’s 0 order kinetics?
phenytoin
= anti epileptic last resort
= very variable from patient-patient dose escalation (common thing to do) = means that from dose-dose it can very quickly flip to 0 kinetic pathway and drug plasma concentration shoots up
what is steady state?
- where we maintain drug plasma concentration within given range
- at steady state you get constant concentration range (may oscillate a bit if non-vascular but IV fully steady)
rate of drug administration (RO) = rate of drug elimination (RE)
how do you calculate dosage for steady state? (roughly - what is involved)
clearance is used to calculate dosage required to maintain drug plasma concentration at steady state
-> if non-vascular ROA then you would have to take bioavailability into account, not for IV as bioavailability 100%
what happens to steady state if drug dose doubled?
steady state also doubled -> adverse drug effects
what can help get to steady state quicker?
loading dose
