2. Defination
Chemical alteration of a drug in living organism is called “biotransfortion”.
Metabolism usually converts the “lipid soluble” and “unionized” into
“water soluble ionized” compounds which are readily excreted by kidneys.
Drug metabolism often converts lipophilic chemical
compounds into more readily excreted hydrophilic products.
If the parent drug from the beginning is water soluble and ionized than it
dose not undergo metabolism and is readily excreted by the kidneys
3. “ Sites of biotransformation”
“ Liver” is the main site of drug metabolism.
Other sites include
a. “GIT”
b. “Kidneys”
c. “Lungs”
d. “Blood”
e. “Skin “
f. “Placenta”
Usually the end result of metabolism is an inactive compound but
sometimes an active compound may also formed.
4. There are four ways by which the activity of a drug can be altered.
1. Active into inactive metabolite
e.g., phenobarbitone ----------- hydroxyphenobarbitone
2 . Active into active metabolite
e.g., codiene -------------------- morphine
diazepam--------------------oxazepam
3. Inactive into active metabolite
e.g., L –Dopa--------------------- Dopamine
prednisone-------------------- Prednisolone
4. Active into highly toxic metabolite
Paracetamol----------------- N- acetyl-p benzoquinoneimine(NAPQI)
5. There are two pathways of drug metabolism.
Phase 1 ( non – synthetic reactions)
Phase 11(synthetic reactions)
6. These include
“Oxidation” : addition of O2 and / or removal of hydrogen.
e.g., phenytoin, propranolol, pentobarbitone, phenobarbitone.
“Reduction”: removal O2 Or addition of hydrogen
e.g., chloramphenicol, methadone.
“Hydrolysis” : Breakdown of compound by addition of water.
e.g., procain , succinylcholine, lignocaine, procainamide
At the end of phase the metabolites may active or inactive .
7.
8. Phase 11reactions include conjugation reactions.
Phase 1 reactions result in the formation of polar ( ionized ) water soluble products
which are readily excreted by the kidneys but some products formed are still lipophillic
and unionized. Such products are reabsorbed and then undergo phase 11 metabolism . In
phase 11 metabolism the products undergo conjugation reactions. Compounds in this
phase are conjugaed with endogenous substances like
Glucoronic acid ,
Sulphuric acid
Acetic acid
Amino acid.
10. All the drugs don't under phase1 reaction initially in fact INH
and some other drugs undergo phase 11 reactions first and
then after that under go phase 1 reactions .
11. 1. microsomal enzymes :
present in reticuloendothelial system of the cells.
Catalyzes phase 1 and glucoronid conjugation.
Is inducible
Include CYP450 and glucoronyl transferase enzyme
2. non microsomal enzyme system:
Found in the cytoplasm, mitochondria of the living cells and in
plasma.
Catalyze all the phase 11 reactions except glucoronid conjugation.
Some of the oxidative and most of the reduction reactions are also
carried out by this system.
This system can undergo polymorphysm and are non inducible.
12. Repeated drug administration may induce the synthesis
of microsomal enymes this is called enzyme induction.
A drug may be an enzyme inducer like Rifampicin,
Barbiturates, Phenytoin, carbamezapine, griesiofulvin.
13. Some drugs inhibit the activity of these enzymes and
are called the enzyme inhibitors.
This is a rapid process as compared to induction.
Chloramphenicol , ciprofloxacin and erythromycin are
the enzyme inhibitors.
