Metabolism Flashcards
metabolism function
- makes substances suitable for renal excretion in urine
- make substances better soluble in water
How does metabolism work?
Enzymes cause chemical transformations in drugs
2 phases in chemical transformation:
- Phase 1: oxidation reaction
- Phase 2: conjugation reaction
What happens whit a phase 1 reaction?
Metabolites become more soluble in water
Which enzymes cause chemical transformations?
CYP enzymes (from cytochrome P450)
Which drug is made inactive and more soluble in water by a phase 1 reaction?
Ibuprofen
Which drug is made inactive and more soluble in water by a phase 2 reaction?
Paracetemol
which is a prodrug and needs to be activated?
Clopidogrel
Factors influencing metabolism
- Age
- Diseases
- Food
- Drugs
- Genetic factors
- Pharmacogenetics
How does age influence CYP-enzyme activity?
the older –> the lower the CYP-activity
Enzyme induction
inducers increase the enzyme activity –> metabolism of the substrate becomes higher
Enzyme inhibition
Inhibitors decrease the enzyme activity –> metabolism of the substrate becomes lower
Enzyme inducers: - Aclohol - Janskruid - Tabaco - Rifampicin - Phenytoin - Carbamazepine Which CYP enzyme do they induce?
- Acohol –> CYP2E1
- Janskruid –> CYP3A4
- Tabaco –> CYP1A
- Rifampicin –> CYP3A4, CYP2C9, CYP2D6
- Phenytoin –> CYP3A4
- Carbamazepine –> CYP2C9, CYP3A, CYP1A2
Enzyme inhibitors: - Grapefruitsap - Ketocozanol - Metronizadol - Verapamil - Miconazole Which CYP enzyme do they inhibit?
- Grapefruitsap –> CYP3A4
- Ketocozanol –> CYP3A4
- Metronizadol –> CYP2C9
- Verapamil –> CYP3A4
- Miconazole –> CYP2C9
Substrates:
- CYP3A
- CYP2C9
- CYP2D6
- CYP3A: cyclosporine, Ca+ channel blocker, midazolam, amiodaron
- CYP2C9: Acenocoumarol, ibuprofen, losartan
- CYP2D6: Codeine, metroprolol, fluoxetine
