Metabolism/Biotransformation Flashcards
Define biotransformation
- changes lipid soluble/non-polar compounds -> H2O soluble/polar compounds so they can be excreted
What happens if biotransformation can’t occur?
Compounds/drugs remain in circulation for a long time -> toxic rxns
Pharmacological inactivation
- Active drug -> inactive or less active state
- Ex. Phenobarbital -> Hydroxyphenobarbital
Bioactivation/ Toxological activation
- active drug -> active metabolite
- Ex. Codeine -> Morphine
Lethal synthesis
Highly toxic metabolite formed from non-toxic precursor
Pharmacological activation
- inactive drug (pro-drug) -> active metaboliteb
- Ex. Enalapril to enalaprilat
Change of active drug to equally active drug is called
- nothing b/c no change in pharmacological activity
- Ex. Diazepam to Nordiazepam
Change from an active drug to active metabolite with an entirely different pharmacological activity is called
- Change in pharmacological activity
- Ex. Ipronizad to Isoniazid
Primary site for metabolism
Liver
Extra-hepatic metabolism
All tissues have some degree of metabolic activities
Where is the most drug metabolizing activity found?
In SER and cytosol
Microsomal drug metabolizing enzymes
- lipophilic membranes of SER
- Glucuronide conjugation: most important enzyme groups, most oxidative rxns, some reductive and hydrolytic rxns
- Inducible drugs
Non-microsomal drug metabolizing enzymes
- mostly in cytoplasm, mitochondria, bodily fluids
- catalyze few oxidative rxns, some reductive and hydrolytic rxns
- all conjugative rxns; no glucuronidation
- non inducible
2 biotransformation pathways
- Phase I: functionalization (non synthetic/ non conjugative)
- Phase II: conjgation (synthetic)
Phase 1 of Biotransformation
- RIG (from chemistry)
- Hydrolysis
- Oxidation (adding polar functional groups)
- Metabolism
