Drug metabolism Phase I Reaction

Phase I Reaction

1. DRUG METABOLISM PART II Dr. P. PARTHIBAN Professor Vellalar College of Pharmacy

2. Points to be discussed Definition Phase –I reactions

3. Drug metabolism is defined as Enzymatic chemical reactions that are responsible for the conversion of drugs into metabolites with in body. (OR) The biochemical modification of one chemical form to another, occurring usually through specialized enzymatic systems.

4. Drug metabolism has been divided into two categories Phase I ( Funtionalization Reaction) Phase II (Conjugation reaction) Phase I They are enzyme biotransformation reaction, in which drug may undergo a wide varity of oxidation , reduction and hydrolysis resulting in introduction or unmasking of functional group ↓ which is ↑ ce the polarity of the molecule and serve as a centre for the second phase of metabolic reaction. It is called as funtionalization reaction.

5. These biotransformations are also called as synthetic reaction, opposite to synthetic phase II reactions. Functional groups -OH (Hydroxyl), -SH ( Thiol ),\ -COOH (Carboxyl), -NH 2 (Amino) are called as xenobiotics ↓ to yield a more water soluble chemical entity.

6. PHASE - I

7. I. OXIDATIVE REACTION (LOSS OF ELECTRON FROM A SUBSTANCE IN A REACTION) Oxidation is a common reaction in xenobiotic . Oxidation reaction increases the hydrophilic of the xenobiotics by introducing the polar functional group (OH). The reaction catalysed by a group of membrane BOUND MONO OXYGENASE ( Cytochrome 450) The enzyme require both molecular OXYGEN (O 2 ) & the reducing agent NADPH to effect reaction. RH + O 2 + NADPH + H + → ROH + H 2 O + NADP +

8. OXIDATION OF AROMATIC CARBON ATOM Aromatic hydroxylation refers to mixed function oxidation of aromatic compounds to their corresponding phenols. The reaction proceeds via formation of reactive intermediate Arene oxide or Arene epoxide , which results in multiple reactions.

9. Oxidation of Olefines Oxidation of non aromatic C-C double bond is analogue to aromatic hydroxylation; it proceeds via epoxide to yield 1,2 dihydrodiol . The epoxide is not very reactive like aromatic epoxide

10. Oxidation of Benzylic carbon Carbon atom attached directly to the aromatic ring ( Benzylic carbon) is hydroxylated to corresponding carbinols or alcoholic metabolite. Primary alcohol metabolite is further oxidized to aldehyde and further to carboxylic acid and secondary carbinol gets converted to ketone by alcohol and aldehyd e dehydrogenase respectively.

11. Oxidation of Allylic carbon Carbon atom adjacent to Olefinic double bonds undergoes hydroxylation similar to benzylic carbon.

12. Oxidation of carbon atom α to Carbonyl and Imines The mixed function oxidase also oxidizes carbon atom adjacent to carbonyl and imino functionalities

13. Oxidation of Aliphatic Carbon Atom Oxidation of Alicylic carbon atom Others oxidation reactions such as, Oxidation involving C-N system (Amines reaction) Oxidation of carbon- sulfur system Oxidation of Alcohol and Aldehyde

14. II. Reduction reactions Important role in metabolism of many compounds containing carbonyl, nitro and Azo group. Bio-reduction of carbonyl group results in alcohol whereas nitro and Azo group give rise to amino group. The amino and Hydroxyl group are more susceptible to conjugate. Reduction of Aldehyde and ketons

15. Reduction of Azo and Nitro compound

16. III. Hydrolytic reactions Hydrolysis of Esters and Amides Hydrolysis of Amide

17. Thank you