Drug Metabolism Flashcards
1
Q
Xenobiotics
A
- Substances foreign to body; usually lipophilic
- Metabolized by xenobiotic metabolizing enzymes (because otherwise they accumulate in adipose and diffuse back into circulation in kidney)
- Where are these enzymes? GI tract (liver, SI, LI), lungs, nasal mucosa
2
Q
First Pass Effect
A
Metabolism in liver
Oral drugs –> SI –> portal circulation –> liver (METABOLISM)
3
Q
Prodrug
A
- compound that requires phase I reaction to be active
4
Q
Phase I Reaction
A
- Usually just make precursors for Phase II by adding functional group
- Minimal inc in hydrophilicity
- Usually slower, rate-limiting step
5
Q
CYP Enzymes
A
Superfamily of enzymes that oxidize substrates - variation b/c genetic polymorphisms- overlapping substrate specificity –> drug/drug or drug/food interactions
6
Q
CYP3A4
A
- Inhibited by grapefruit –> inc in bioavailability of drugs that are normally metabolized by CYP3A4
- Induced by St John’s Warts –> dec in bioavailability of drugs that are normally metabolized by CYP3A4
7
Q
Phase II Reaction
A
- Conjugation that requires functional group usually added by phase I
- Sig increase hydrophilicity of substrate -inc accumulation in aqueous compartments of body
- Faster step
- Ex) glucoronidation and glutathione conjugation
8
Q
UGTs
A
catalyze transfer glucouronic acid to form glucuronide conjugate - now excreted in kidney or bile
9
Q
UGT1A
A
- Enzyme that metabolizes/eliminates bilirubin
- Genetic variation –> hyperbilirubinemia/ jaundice
- At risk for ADR w/ UGT1A1 substrates that may compete w/ bilirubin or drugs that inhibit the UGT1A1 that they do have
- Less extreme version - GIlbert’s syndrome (10% of population)
10
Q
Acetaminophen Toxicity
A
- High acetaminophen –> reacts w/ GSH (glutathione) –> NAPQI (toxic metabolite) accumulates and glutathione depletion and nephrosis
- Treat w/ glutathion precursor
11
Q
GSTs
A
catalyze transfer glutathione to electrophiles
