Drug Metabolism Flashcards
1
Q
drug metabolism
A
- chemical transformation of drug within living organism
- =drug biotransformation
- most =enzyme based but some arent
- makes drugs more hydrophillic which is needed for excretion
2
Q
drug metabolism and inactivation
A
- change active drug to inactive
- change lipid soluble to less lipid soluble to facilitate excretion via kidney
- chemical modification of drug terminates activity
3
Q
activation and drug metabolism
A
- metabolism can change an inactive drug to an active metabolite or a toxic metabolite
- can maintain active drug to active metabolite
4
Q
cellular level of drug metabolism
A
- hepatocyte (cytoplasm)
- intestinal epithelial cell
- mitochondria
- ER
- lysosome
- plasma mb
5
Q
phase I reactions
A
- activity = equal, lower, or higher
- functional groups = NH (amine), OH (hydroxyl), or SH (sulfhydral)
6
Q
phase II reactions
A
- enzymes are often in the cytoplasm
- activity = lower
- glucuronic acid
- glutathione
- sulfate group
- acetyl group
7
Q
Main phase I reactions
A
- microsomal oxidation: hydroxylation reactions
- non-microsomal oxidation - alcohol oxidation
- hydrolysis reactions: esterases and amidases
8
Q
cytochrome P450 enzymes
A
- family of enzymes (57 isoforms)
- mainly found in ER (liver and intestine)
- mixed function oxidase (MFO) system used in microsomal oxidations of phase I reactions
9
Q
microsomal fraction
A
- isolated by tissue homogenization and differential centrifugation
- pellet - vesicles formed from ER mb : microsomes
- useful for in-vitro studies
- assign P450 enzymes to drug: promiscuity
10
Q
cytochroe P450 cycle
A
- RH + O2 + NADPH + H+ —— ROH + H2O + NADP+
- oxygen gets incorporated into hydroxyl group and water
- Iron involved in redox reaction
11
Q
how is alcohol metabolized
A
- alcohol dehydogenase mainly (non-microsomal oxidation)
- some by catalase and CYP2E1
12
Q
If status of an enzyme changes, that will adjust how things are ______
A
metabolized
13
Q
PABA
A
- PABA is a metabolite of esterase and amidase reactions
- structurally similar to sulfonamides (antimicrobial)
- will compete with sulfonamide for drug site of action and lead to reduced therapeutic effectiveness
14
Q
oxidation reactions (phase I) often precede conjugation (phase II) because the generated _____ group during phase I reaction is easily conjugated with several compouds
A
hydroxyl group
15
Q
factors affecting drug metabolism
A
- drug-age interactions (differential expression of enzymes)
- drug-drug incompatibilities (competitive inhibition, induction=pharmacokinetic tolerance)
- drug-endogenous substrate interactions (competition with endogenous substrate)
- drug disease interaction (liver disease= impact on microsomal oxidases, cardiac disease = impact on hepatic blood flow)
- drug-genetic interactions (gene mutations, different metabolism rates)
