Biotransformation Flashcards
(22 cards)
What is biotransformation ?
• It is the biological alteration mechanism by which the drugs are inactivated.
• An enzymatically mediated process.
What is the three major routs of elimination ?
Hepatic metabolism
Bile
Urine
Give an example of a drug administered inactive then come active ?
Codeine»_space; morphine
What’s the aims of metabolism ?
Metabolism => Termination of Drug Action
Bio inactivation
Detoxification
Elimination of drugs effects
Site of metabolism
The liver is the major site for drug metabolism.
• Other tissues include the gastrointestinal tract, the skin, and the lungs. kiang, brain
Site of metabolism within the cell
endoplasmic reticulum
cytosol.
mitochondria
nuclear envelope
plasma membrane
How ER break up ?
Upon homogenization and differential centrifugation of tissues
ER when break form microvesicles , what’s the name of these vesicles and what it contain ?
Microsome
And they contain DME ( microsomal enzyme )
What is the phrases of metabolism ?
Phase 1 : functionalization
Phase 2 : conjugation
When phases occur ?
Phase 1 occur btw absorption and metabolism
Phase 2 occur btw metabolism and elimination
What is phase 1 , what is the aims of it ?
Converts the parent drug to a more polar metabolite by introducing a functional group (-OH, -NH, -SH). Often these metabolites are inactive
Aims:
• Enhance excretion
(more water soluble)
• Prepare for phase 2
(functional handle)
What phase 1 include ?
Oxidations (O2)
• Reductions (Reducing agent NADPH)
• Hydrolyses (Formation of H2O)
Microsomal enzyme
Found in ER
- catalyst phase I and Il glucuronide conjugation reaction)
- include cytochrome p 450
-they are inducible
Non microsomal enzyme
Found in cytoplasm, plasm, mito of liver
- Catalyze All phase 2 except glucronide conjugation
- most are reduction and hydrolysis denchor
- Show genetic polymorphism
- not inducible
What’s the enzyme in microsome ?
mixed function oxidases (MFOs) or the monooxygenases.
What MFO require ?
Cytochrome P450 (CYP)
Cytochrome P450 reductase
NADPH
> Molecular oxygen:
1 reduced per sub
1 apperig in the product
1 form of water
Cytochrome p 450
Hemoprotien
Terminal oxidase of oxidation- reduction reaction
Have multiple forms in microsomal membrane ( isoforms - isozymes ) >1000
When dose multiplicity of CYP increase ? And give example
It’s increase by repeated exposure to exogenous chemicals and repeated administration
Ex :
CYP2B1induced by phenobhbitone treatment.
CYP1A1 induced by polycyclic aromatic hydrocarbons.
What is phase 2?
Act on parent drug or on phase 1 metabolite that contain chemical groups, link to endogenous substans
Its involve transferase enzyme located in microsome, cytosol
Example of endogenous substans?
Glucuronic acid
Sulfuric acid
Acetic acid
Amino acid
What’s the function of transferase enzymes?
Attach drug to endogenous substances
Reactions of phase2?
Glucruronidation, MOST IMPORTANT
glutathein conjugation,
Acatelation,
Glycine conjugation
Sulphate formation
Methylation
