Drug Biotransformation Flashcards
What property do drugs generally express?
Generally lipophilic
What does metabolism do to drugs to allow them to be excreted by the kidneys?
Makes the drugs more polar and water soluble
Usually makes drugs less active, but can enhance activity
What is the principal organ of drug metabolism? What is the second most important?
Principal organ is the liver, followed by the GI tract
*Every tissue can metabolize drugs
What is the purpose of phase 1 reactions?
To introduce or unmask a functional group. Goal is to inactivate a drug.
What are the 3 primary processes of Phase 1 reactions?
- Oxidation
- Reduction
- Hydrolysis
What system of enzymes is most frequently involved in drug metabolism?
The CYP450 enzyme system
What is the CYP450 system?
A super family of heme-containing isozymes located in most cells
Where is the CYP450 system primarily located?
In the liver and GI tract
What percentage of prescription drug metabolism is the CYP450 enzyme system responsible for?
Over 50%
Y/N Do genetic variabilities (polymorphisms) exist within the CYP450 system?
Yes
When do Phase 2 reactions take place?
If the product of phase 1 oxidation/reduction/hydrolysis is not adequately polar (if it is it can be excreted by kidneys)
If the molecule is not adequately polar, what do Phase 2 reactions do?
“Conjugates”, attaches an endogenous substance
What molecules attach the polar endogenous substance to the drug in phase 2 reactions?
Transferases
What are the 3 types of Phase 2 reactions?
- Glucuronidation- MOST COMMON
- Acetylation
- Sulfation
What are the three Phase 1 Enzymes?
- CYP450 enzymes
- Flavin-containing monooxygenases
- Epoxide hydrolases
