Metabolism/ Biotransformation Flashcards
Biotransformation
Converts lipid soluble and non-polar compounds to water soluble and polar compounds so they’re easily excreted and absorbed
What happens when a substance isn’t converted to a water-soluble form?
Remains in body for a long period of time –> toxic reaction
Active drug to inactive
Majority of drugs
Inactivation or pharmacological inactivation
Ex: phenobartbital to hydrocyphenobarbital
Active drug to more active
Bioactivation or toxicological activation (could cause toxicity)
Ex: codeine to morphine, malathion to malaxon
Inactive (pro-drug) to active metabolite
Pharmacological activation
Given because active compound isn’t always stable
ex: enalapril to enalaprilat or phenacetin to acetaminophen
Active drug to equally active metabolite
No change in pharmacological activity
ex: digitoxin to digoxin, diazepam to nordiazepam
Active drug to active metabolite
Having entirely different pharmacological activity
ex: iproniazed (antidepressant) to isoniazid (anti tubercular)
________ is the primary site of metabolism
LIVER
Where is most drug metabolizing activity found in the cell?
Smooth ER and cytosol
Microsomal drug metabolizing enzymes
In lilophilic membranes of the SER
Most imp: glucuronide conjugation
Inucible by drugs, diets
Non-microsomal drug metabolizing enzymes
In cytoplasm, mito, body fluids (liver, GI, plasma)
All conjugative reactions
Non-inducible
Phase 1 pathway of biotransformation
Functionalization = reduction, hydrolysis, oxidation
Reduction
Addition of hydrogen to the drug molecule
Hydrolysis
Cleavage of drug molecules by taking up a molecule of water
Oxidation
Introducing polar functional groups (OH) by microsomal enzymes (MFO or CYP-450)
