What are the two ways drugs are eliminated?
- Metabolism (biotransformation)
- Excretion
How does metabolism affect elimination?
Biotransformation by metabolism normally terminates pharmacological activity, making the drug easier to excrete.
What are the 2 phases of metabolism?
- Phase I - formation of new or modified functional group of cleavage (oxidation, reduction, hydrolysis)
- Phase II - reactions involving conjugation with endogenous particles
This leads to more polar compounds with reduced lipid solubility resulting in more rapid excretion in bile or urine.
Where does metabolism occur?
Enzymes involved in metabolism are present in many tissues but more concentrated at liver.
Where does excretion occur?
- Kidney (renal excretion to urine)
- Liver (bile)
What is hepatic secretion?
Drug is secreted into bile and excreted. It may be reabsorbed in intestine, entering enterohepatic circulation.
What is renal excretion?
The primary route of drug excretion.
- Filtration in the glomerulus (network of capillaries in kidney, first stage of filtering process in formation of urine)
- Tubular secretion - separate active transport system in proximal tubular cells
- Reabsorption
What individual variations affect metabolism and excretion?
- Age - decline in renal clearance, general metabolism impairment
- Renal disease
- Liver disease
- Competition with other drugs
What affect does rate of elimination have on action of drug?
The slower the rate of elimination, the longer the amount of time in the body, more of an effect in CNS.
