Drug Elimination Flashcards
Excretion
Removal of drugs or metabolites from the body.
Elimination
Excretion or inactivation of drug by metabolism
Hydrophilic drugs
can be excreted via urine w/out metabolism
Kidneys
Major route of excretion of most drugs.
Most have to be metabolized b4.
High blood flow
Clears blood of drug by FILTRATION and ACTIVE SECRETION
The three processes that predominate excretion via the kidney;
Filtration, Reabsorption, Secretion
Filtration via the kidney
Same clearance of plasma compounds (creatinine is classic clearance substance).
What is favoured to be excreted by the kidney?
Polar drugs and metabolites
The low pH of urine traps weak bases, which can speed up elimination/detox.
Secretion via the kidney
Some drugs secreted into proximal tubules.
Penicillin 90% of elimination is secretion.
Secretion results:
Rapid elimination and high concentrations in bladder.
In the liver:
Elimination: deactivates through metabolism.
Prepars many lipophilics for renal excretion.
Prepares some drugs for biliary excretion.
Hepatic metabolism/biotransformation:
Enzymes breakdown or transform drug molecules.
Elimination by the liver
Can secrete drugs or its metabolites into bile which is then secreted into intestines.
Enterohepatic cycling:
most of what is secreted with the bile into the intestines is reabsorbed by the intestines.
Unabsorbed drugs or drugs not reabsorbed:
Go out with feces.
Elimination by lungs
Important for elimination of general anesthetics.
Lungs eliminate gases and not much else
Measuring elimination
Most commonly used measure ishalf life.
Clearance
Theoretical amt of blood totally cleared of drug in a given time.
mL/min
Only drugs w 1st order elimination have constant clearance rate.
Half-life determined by
Clearance and volume of distribution
t1/2=(Vd*0.7)/Cl
Cl is a measure of the function of elimininating organ.
Vd is a measure of the fraction of drug in blood
Clearance (defines)
Defines the rate at which a drug must adminstered to achieve a desired concentration
Renal clearance
If a drug has a Cl of approximately 120 ml/min has a rate of elimination roughly equivalent to filtration: no reabsorption, no tubal secretion.
If a drug has a Cl of approximately 720 ml/min it has a rate of elimination roughly equivalent to renal plasma flow=tubal secretion, no reabsorption.
1st order elimination
Almost all drugs.
The amt of drug eliminated proportional to concentration in blood.
Fraction of drug eliminated is constant.
Constant half-life
If it is decreased at t1/2 by 1/3 it will keep doing so at hour two, three, four, etc.
Zero order elimination
Like alcohol
No half life
Constant amt eliminated over time
Zero order elimination details
[Drug] overwhelms mechanism of elimination.
Only very few drugs that are effective at high concentrations., or drugs at toxic concentrations.
Since it has no constant half life, if it is eliminated at a 100ug/ml/hr it will do so forever.
