elimination
removal of drug from plasma resulting in a decrease in conc
metabolism
enzymatic process that alters the chemical structure of a drug
changes drug from lipophilic to a metabolite that is hydrophilic
factors that alter metabolism
-species/breed
-environmental factors
-age
-dz state/ other drugs (drug-drug interactions)
-genetic polymorphisms
consequences of drug biotransformation
-formation of an inactive polar metabolite
-formation of an active metabolite
-formation of a reactive/toxic metabolite
Biotransformation of drugs usually makes them?
less lipid soluble
metabolic enzymes
-speed up rate of rxns
-many require cofactors/coenzymes
-substrate specificity
-multiple enzymes may metabolize a single drug
Extrahepatic microsomal enzymes
(oxidation and glucuronidation): Lungs, brain, skin?, pancreas? Intestine?
Hepatic microsomal enzymes
...
Hepatic non-microsomal enzymes
...
phase I rxn
introduces a reactive group
Phase II rxn
attaches a polar molecule (conjugation)
Phase I rxns main types
-hydrolysis
-reduction (gain of a hydrogen or removal of a what??)
-oxidation
Which of the following statements in NOT true about cytochrome P450 enzyme?
A. These are phase 2 enzymes
Phase II metabolism
-substrates may arise from phase I metabolism
-usually metabolites have decreased biologic activity
-metabolites are highly polar
-some metabolites are excreted in bile
hepatic clearance
volume of plasma flowing through the liver that is completely cleared of a drug per unit time
hepatic clearance affected by
-hepatic extraction
??