Definition, Introduction and Types

1. PART I
Dr. P. PARTHIBAN
Professor
Vellalar College of Pharmacy

2. Points to be discussed
 Definition
 Introduction
 Types

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 or biotransformation refers to
modification of xenobiotic in the biological system
 All the chemical substances that are not nutrients
which enter the body through ingestion,
inhalation/ absorption are called as xenobiotics or
exogenous compound.
 Drugs are also xenobiotics by virtue (nearly as
described, but not completely) of their lipophilicity.

5.  Water soluble agents
ie. Lipid soluble substances are reabsorbed from
the renal tube into the blood after glomerular
filtration.
↓ (Continue)
Drug would accumulate in the body & precipitate
toxic reaction.
However, to prevent such a consequence, the water
insoluble lipophilic nonpolar drug into polar and
water soluble product that can be easily excreted by
the kidney.
The enzymatic biotransformation is known as drug
metabolism (Detoxification process)

6.  Drug metabolism occurs in all the tissues, but the
principle site of drug metabolism is the Liver, the
other sites are Kidney, Lungs, GIT, Brain, Placenta
& Skin.
 Orally administrated drugs are absorbed through
mucous membrane of the small intestine or
stomach.
 Once out of GIT tract, it is carried by the blood
stream to the liver, when it is usually first
metabolized.

7.  Metabolism by liver enzyme prior to the drug
reaching the systemic circulation is called as the
first pass metabolism/presystemic/first pass effect,
which may result in complete deactivation of drug.
Eg. Imipramine, Morphine, Propranolol,
Diazepam, Midazolam, Cimiditine &
Lidocaine.
 First pass effect can be avoided by changing the
route of administration like,
Suppository, IV, IM, inhalational aerosol,
Transdermal and sublingual.

8.  Nitroglycerin used in the treatment of angina
pectoris is given sublingual route to bypass the
liver.
 Most of the drugs are administered orally.
 The enzymes present in the body plays an
important role in extra hepatic metabolism
xenobiotic.
Eg. Esterase and Lipase present in the
intestine, hydrolyses many esters.
 Prodrug and bacterial flora reduces many AZO
and Nitro drugs (sulfasalazine)

9.  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.

10.  These biotransformations are also called as
synthetic reaction, opposite to synthetic phase II
reactions.
 Functional groups -OH (Hydroxyl), -SH (Thiol),
-COOH (Carboxyl), -NH2 (Amino) are called as
xenobiotics
↓ to yield
a more water soluble chemical entity.

11. Phase I accomplished by-
 Direct introduction of the functional moiety.
 Aliphatic or Aromatic hydroxylation
 Modifying or “unmasking” prevailing functionalities
 Reduction of Azo (-N=N-) and (-NO2) Nitro compounds
to produce Amino (NH2) group.
 Oxidative N-,O- and S- dealkylation to yield respective
NH2, OH and SH moiety.

12. Phase II also called as conjugation reactions
 The original unaltered drug or polar metabolite is
conjugated to glucuronic acid, sulphate, amino
acid, acetyl or methyl group making the molecule
more polar soluble and therefore it is readily
excreted.
Salient features of conjugated metabolites
 Do have a tendency to get excreted rapidly in the
wine.
 Generally found to be more pharmacological
activity profile and toxicity in humans.

13.  It has been duly observed that certain phase II
pathways produce pharmacological activity
significantly.
Eg. Acetylation, Methylation do either
terminate in inherent biological activity.
COOH
OCOCH3
CONHCH2COOH
OH
COOH
OH
Phase-I Phase-II
Aspirin Salicylic acid Salicyluric acid
NH2CH2COOH
Conjugation
with Glycine

14. Next class point to be discussed
Phase-I Reactions
Thank you