This ppt presentation describes briefly about drug metabolism, influencing factors on drug metabolism and the purpose of drug metabolism.

1.  DR. R. MALLIKA
 ASSOCIATE PROFESSOR
 DEPARTMENT OF BIOCHEMISTRY
 V.V.VANNIAPERUMAL COLLEGE FOR WOMEN,
 VIRUDHUNAGAR

2. Drug metabolism description of the biotransformation of
pharmaceutical substances in the body.
Biotransformation enables easy elimination
The majority of metabolic processes of drugs occur in the liver
T he enzymes that facilitate the reactions are concentrated in liver.

3.  The purpose of metabolism in the body is to change the chemical
structure of the substance that will enhance elimination from the body.
Drugs are metabolized through various reactions including:
 Oxidation
 Reduction
 Hydrolysis
 Hydration
 Conjugation
 Condensation
 Isomerization

4.  When a drug gets metabolized it becomes inactivated in majority of
cases.
 The metabolites of some drugs are pharmacologically active and
exert an effect on the body.
 The active metabolite of some medications is responsible for the
principal action of the drug and this drug formulation is referred to
as prodrug.

5.  Patient Variability
 The rate of drug metabolism vary significantly for different
patients, which affects the efficacy and toxicity of the drug.
 Rapid metabolizers clear the drug very quickly, and the therapeutic
concentration of the drug in the blood and tissues may not be
reached.
 In slow metabolizers, the drug accumulates in the blood stream.
creates a greater potential for adverse effects.

6.  The factors related to patients which affect the rate of
metabolism include:
• a genetic predisposition
• chronic liver disorders
• advanced heart failure
• interactions with other concurrent medications

7.  Two phases of drug metabolism.
• Phase I: Non-synthetic reactions such as cleavage (e.g. oxidation,
reduction, hydrolysis), formation or modification of a functional group.
• Phase II: Synthetic reactions like conjugation with an endogenous
substance (e.g. sulfate, glycine, glucuronic acid).
• Metabolites formed in Phase II by synthetic reactions are more polar,
and be excreted in the urine or bile more easily.

8.  Drug Metabolic Rate
 There is an upper limit for the rate of drug metabolism in majority
of drugs.
 Due to the saturation of the enzymes needed for the metabolic
pathway
 The therapeutic doses usually used are significantly below the level
of saturation of Enzymes
 The metabolic rate increases with the concentration of the drug. This
is referred to as first-order kinetics.

9. The metabolism rate is a constant fraction of the
concentration of the drug in the body.
Therapeutic doses of the drug lead to the saturation of
the enzyme sites.
the metabolism remains constant despite increases in
the dose of the drug, in such cases. This is referred to
as zero-order kinetics.

10.  The most common enzyme group involved in the Phase I metabolism of drugs is the
cytochrome P450 (CYP450) superfamily of enzymes.
 These enzymes acts as a catalyst for the oxidation of many drugs.
 Induced or inhibited by many drugs and other substances. As a result, the metabolism of
some drugs is affected by the presence of other substances which is kmown as a drug
interaction.
 Some of the important enzymes in this family include:
• CYP1A2
• CYP2C9
• CYP2C19
• CYP2D6
• CYP2E1
• CYP3A4

11.  Many drugs and other substances found in foods
or herbal remedies affect these enzymes and
change the rate of metabolism of drugs.
 With aging, the capacity of the CYP450
metabolism decreases by at least 30%, probably
due to changes in the hepatic volume and blood
flow.
 Hence, the dosage of drugs needs to be reduced
in elderly patients.

12.  Glucuronidation is the most common type of phase II reaction, and
occurs in the microsomal enzyme system of the liver.
 This reaction increases the solubility of the drugs so that drugs can
be secreted in the bile or urine.
 Aging does not affect the metabolic rate of glucuronidation and
there is no need to reduce the dose of such drugs for metabolic
reasons in the elderly.

13. THANK YOU