Drug Metabolism Flashcards
What is the function of inactivation?
Facilitate elimination - inactive metabolite is more easily eliminated. Lipid-soluble (hydrophobic) drugs converted to water soluble (hydrophilic) metabolite.
Where does drug metabolism primarily occur?
Liver
Where does drug elimination primarily occur?
Kidney
Where are Phase I enzymes found?
Mainly endoplasmic reticulum
Where are Phase II enzymes found?
Mainly cytoplasm
What occurs during Phase I?
Drugs are made more hydrophilic and the addition of functional groups
What occurs during Phase II?
Conjugation with endogenous substances occurs onto the functional group
What is the main system that mediates Phase I reactions?
Mixed Function Oxidase System (MFO)
What are the 4 main elements of the MFO?
- Cytochrome P450 Hemoprotein
- NADPH Cytochrome P450 Reductase
- NADPH
- O2
What is the fate of O2 during the MFO reactions?
One O atom is placed onto the drug and one O atom is turned into H2O.
What does non-microsomal oxidation occur on?
Alcohol
What is the function of conjugations in Phase II?
Create a highly polar conjugate to excrete
First-pass effect
Many orally administered drugs will be extensively biotransformed before they reach the systemic circulation due to biotransformation in the G.I. tract and liver
What is the net equation of the Phase I reaction?
RH + O2 + NADPH + H+ -> ROH + H2O + NADP+
What is PABA structurally similar to?
Sulfonamides