Biotransformation

Question 1

What is biotransformation ?

Answer 1

• It is the biological alteration mechanism by which the drugs are inactivated.
• An enzymatically mediated process.

Question 2

What is the three major routs of elimination ?

Answer 2

Hepatic metabolism
Bile
Urine

Question 3

Give an example of a drug administered inactive then come active ?

Answer 3

Codeine&raquo_space; morphine

Question 4

What’s the aims of metabolism ?

Answer 4

Metabolism => Termination of Drug Action
Bio inactivation
Detoxification
Elimination of drugs effects

Question 5

Site of metabolism

Answer 5

The liver is the major site for drug metabolism.
• Other tissues include the gastrointestinal tract, the skin, and the lungs. kiang, brain

Question 6

Site of metabolism within the cell

Answer 6

endoplasmic reticulum
cytosol.
mitochondria
nuclear envelope
plasma membrane

Question 7

How ER break up ?

Answer 7

Upon homogenization and differential centrifugation of tissues

Question 8

ER when break form microvesicles , what’s the name of these vesicles and what it contain ?

Answer 8

Microsome
And they contain DME ( microsomal enzyme )

Question 9

What is the phrases of metabolism ?

Answer 9

Phase 1 : functionalization
Phase 2 : conjugation

Question 10

When phases occur ?

Answer 10

Phase 1 occur btw absorption and metabolism
Phase 2 occur btw metabolism and elimination

Question 11

What is phase 1 , what is the aims of it ?

Answer 11

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)

Question 12

What phase 1 include ?

Answer 12

Oxidations (O2)
• Reductions (Reducing agent NADPH)
• Hydrolyses (Formation of H2O)

Question 13

Microsomal enzyme

Answer 13

Found in ER
- catalyst phase I and Il glucuronide conjugation reaction)
- include cytochrome p 450
-they are inducible

Question 14

Non microsomal enzyme

Answer 14

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

Question 15

What’s the enzyme in microsome ?

Answer 15

mixed function oxidases (MFOs) or the monooxygenases.

Question 16

What MFO require ?

Answer 16

Cytochrome P450 (CYP)
Cytochrome P450 reductase
NADPH
> Molecular oxygen:
1 reduced per sub
1 apperig in the product
1 form of water

Question 17

Cytochrome p 450

Answer 17

Hemoprotien
Terminal oxidase of oxidation- reduction reaction
Have multiple forms in microsomal membrane ( isoforms - isozymes ) >1000

Question 18

When dose multiplicity of CYP increase ? And give example

Answer 18

It’s increase by repeated exposure to exogenous chemicals and repeated administration

Ex :
CYP2B1induced by phenobhbitone treatment.

CYP1A1 induced by polycyclic aromatic hydrocarbons.

Question 19

What is phase 2?

Answer 19

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

Question 20

Example of endogenous substans?

Answer 20

Glucuronic acid
Sulfuric acid
Acetic acid
Amino acid

Question 21

What’s the function of transferase enzymes?

Answer 21

Attach drug to endogenous substances

Question 22

Reactions of phase2?

Answer 22

Glucruronidation, MOST IMPORTANT
glutathein conjugation,
Acatelation,
Glycine conjugation
Sulphate formation
Methylation