Medicinal chemistry -l-Second year-Fourth semester - Medichem drug metabolism lecture 3 new.pptx

1. MEDICINAL CHEMISTRY I
LECTURE III
BY- MANJUSHA SK
ASSOCIATE PROFESSOR

2. DRUG METABOLISM
• DRUG METABOLISM –
• Metabolism is the process which terminates the actions of the drug and helps in its excretion from the body.
• Drug metabolism usually leads to detoxification as it abolishes the effects of the drugs.
• Drugs when taken orally gets absorbed and goes to the systemic circulation and then passes through the liver.
• Various enzymes are present in the liver which causes metabolism of the drug molecule.
• Metabolism is defined as the process by which drug molecules gets altered in the body.
• Drug metabolism occur by 2 ways :
• Phase-l reactions (functionalization)
• Phase-ll reactions (conjugation)

3. Phase-l reaction
• Phase-l reaction It convert the parent drug into more polar Metabolite by introducing a polar
functional group like —OH, —NH2 —SH -COOH etc. in the drug molecule by various reactions like
oxidation, reduction and hydrolysis.
A) OXIDATIVE REACTIONS – The main enzyme involved in oxidative metabolism is Cytochrome P450 .
• this enzyme is a heme-protein located in endoplasmic reticulum.
B) REDUCTION - Drug containing nitro, azo and carbonyl groups can be easily reduced by various enzymes present
in the body.
C) HYDROLYSIS – It can be done by various hydrolytic enzymes
present in plasma and various tissues.
• It is most common in drugs having ester or
amide functional groups.

4. Phase-ll reaction
• Phase- ll reaction converts the metabolites of phase l reactions with polar functional groups into more polar
and water soluble products.
• The products obtained by phase-ll reactions are generally inactive.
• It carried out by following ways glucuronidation,glutathione copnjugation,sulphate
conjugation,methylation,acetylation,aminoacid conjugation.
• A) GLUCURONIDATION -It is also known as glucuronic acid conjugation reaction. Phase-I metabolites
having COOH free alcoholic or phenolic groups or any drug having these functional groups conjugates with
glucuronic acid to form ether or ester glucuronides.
• Glucuronidation process is done by the help of the enzyme glucuronyl transferase which catalyses this
reaction.
B) GLUTATHIONE CONJUGATION – It is present in most of the tissues.The –SH group present in it reacts
easily with electron deficient compound to give an glutathione product.
This is carried out by the enzyme glutathione 3- transferase.

5. C) SULPHATE CONJUGATION – Drugs having OH,phenol and aromatic amines undergo sulphate
conjugation.
• It can carried out by an enzyme sulphotransferase.
D) METHYLATION –The methyl group is required for methylation reaction. Enzyme methyl transferase is
required for the above reaction
E) ACETYLATION– It involves conjugation with acetyl co-A by the use of enzyme N- acetyl transferase.
• Drug containing amino group undergo acetylation.
F) AMINO ACID CONJUGATION – Drugs having aromatic and arylalkyl acids undergo conjugation with
amino acids.For this process ATP and coenzyme A are required.

6. FACTORS AFFECTING DRUG METABOLISM
A large number of physical, chemical and biological factors affect the metabolism of a
drug. In that the
1. Physiochemical properties of the drug molecule : Physiochemical properties like
molecular size and shape, acidity and basicity, lipophillic character, solubility, pka
value and steric character of drug molecule affects its metabolism.
1. Chemical factors : The various chemical affects the metabolism of the drug. The presence of
Enzyme inducers and enzyme inhibitors alters the actions of drug metabolising enzymes.
• Enzyme inducers- are the chemicals and drugs which increases the activity/ability of
enzymes.eg.alcohol increases metabolism of coumarin and phenytoin.
• Enzyme inhibiters- are the chemicals and drugs which decreases the activity/ability of
enzymes.eg,various halogenated pesticides/heavy metals decreases metabolism of various drugs.

7. 3.Environmental factors : It includes pressure,temperature,humidity etc.affects drug metabolism.
4.Biological factors : It includes age of the patient,diet,sex,species and altered physiological state like disease
state, hormonal imbalance etc. also affects drug metabolism.
5.Steriochemical aspects of the drug molecule : These aspects also affects the metabolism by different enzymes.
Metabolising enzymes have different preferences for each enantiomers hence the result may vary.
For example, (-) quinine treats the malaria fever but (+) quinine does not.

8. THANK YOU