Drug Metabolism Flashcards
Factors affecting drug metabolism
- Enzyme induction
- Enzyme inhibition
- Age
- Enterohepatic cycling
- Nutrition
- Intestinal flora
Types of enzyme inhibitors
Competitive - quinidine (CYP2D6)
Non-competitive- ketoconazole (CYP3A4)
Mechanism-based - gestodene (CYP3A4), diethylcarbamazepine (CYP2E1)
Drugs that undergo EHC
Colchicine
Tetracycline
Phenytoin
Location of metabolizing enzymes
Liver: endoplasmic reticulum membrane of the liver
GIT: epithelial cells of the GIT (e.g. tyramine),
Lungs (e.g. prostanoids),
kidneys, plasma (e.g suxamethonium) and the
Skin.
Examples of metabolizing enzymes
- Xanthine oxidase
- Alcohol dehydrogenase
- Monoamine oxidase
- UDP glucuronyl transferase
- Cytochrome P450 enzymes
Structure of CYP450
Made up of heme proteins but differ in their amino acid sequence, reactions (both oxidation and reduction), and in their sensitivity to enzyme inducers/inhibitors.
Effects of drug metabolism
- Active metabolites
- Altered pharmacological action
- Similar pharmacological action
- Toxic metabolite
- Active, but less toxic metabolite
Limitations of FPE
- Larger doses required
- Unpredictable response due to genetics
Xtics of metabolic rxns
- Which rxns are involved?
- Catabolic?
- Which group?
- Lipid solubility of metabolite
- What comes next?
Metabolized by oxidation
Paracetamol, Steroids
Metabolized by reduction
Disulfiram, Norgestrel
Metabolized by hydrolysis
Lidocaine, Aspirin
Metabolized by glucuronidation
Morphine
Entities involved in glucuronidation
UDP glucuronosyl transferase
UDP glucuronic acid
Glucuronic acid is added
Metabolized by glutathione conjugation
Paracetamol
