Cytochrome P-450 (CYP) enzymes are crucial for drug metabolism, cholesterol, and lipid biosynthesis, primarily in the liver, but also in other tissues. Drug interactions involving CYP enzymes can lead to altered drug effectiveness or toxicity through mechanisms of enzyme inhibition and induction, where one drug affects the metabolism of another. Inhibition can occur in several ways, including competitive or non-competitive mechanisms, while induction by certain drugs or pollutants can enhance the metabolism of other substrates.

2. INTRODUCTION ABOUT CYTOCHROME P-450.
 Cytochrome P450 (CYP) enzymes are a large family of heme-thiolate monooxygenases
found primarily in the liver, but also present in other tissues such as the intestines, lungs, and
kidneys.
 They play a crucial role in the metabolism of drugs and other xenobiotics, as well as in the
biosynthesis of cholesterol, steroids, and other lipids. Drug interactions involving CYP
enzymes are a significant concern in clinical pharmacology, as they can lead to altered drug
efficacy or increased toxicity.
 These enzyme are responsible for breakdown of wide range of substances including
medications, toxins, even Hormones. i.e.., endogenous compound. They need NADPH and
O2 for their work or action.
 This cause rise or decline i.e., alternation in the blood level and efficacy of the affected drug,
potentially leading to the ADR effect or therapeutic failure. Many drug interaction are result
in Drug inhibition or induction of CYP enzyme.
 Drug interaction, involving Cytochrome P-450 enzyme occurs, when one drug affect the
metabolisms of another drug by inducing or inhibiting the activity of specific Cytochrome P-
450 enzyme.

3. MECHANISMS OF DRUG INTERACTIONS
 Drug interactions involving CYP enzymes can occur via two main mechanisms:
enzyme inhibition and enzyme induction
Drug
interaction
Drug
Inhibition
Non-
Competitive
inhibitor
Competitive
inhibitor
Un-
Competitive
Inhibitor
Drug
Induction

4. ENZYME INHIBITION
 Inhibition of CYP-450 by different drug or diff-diff drug interaction is called Inhibition.
 If two drug are substrate for same CYP is-enzyme then metabolism of one or both the
drugs may be delayed.
 Example :- Erythromycin and midazolam both are substrate of 3A4 isoenzyme. So there
is competition for binding site and at last metabolisms of midazolam in inhibition.
 Cimitidine and Ketoconazole binds to Cytochrome P-450 and completely inhibit the
metabolism of Testosterone.

5. TYPES OF ENZYME INHIBITION
Types of
Enzyme
Inhibition
Competitive
inhibitor
Non-
Competitive
inhibitor
Un-
Competitive
Inhibitor

6. Binds to the Active site
Km = Increase
Vmax = No effect (It
remain same)
Eg:- statin drugs
Competitive in
HMG-CO- Reeducates
enzyme
For
cholesterol synthesis
Binds to the Allosteric
site
Km = unchanged
Vmax = Decrease
Eg., Heavy metal
(Mercury)
Binds to sulfhydryl
group on enzyme.
Binds to the Allosteric
site
Km = Decrease
Vmax = Decrease
Eg., Certain drug used
for Cancer Treatment.

7. DRUG INDUCTION
 Induction of CYP-450 enzyme by drugs and pollutants
 Some certain drugs can induce the activity of specific CYP-450 enzymes, resulting in
increased metabolisms of other drugs that are substrate for those enzymes.
 Example:- Phenobarbitone, Rifampicin (CYP3A4 inducer), Smoking (IA2 inducer i.e..,
Theophylline), DDT, Alcohol, Phenytoin (CYP2C9 Inducer)
Drug Induction
Auto induction
If a drug
induces its own
metabolism =
Auto induction
Eg :-
Carbamazapine
Foreign induction
If the induction
by other
compound =
foreign induction
Eg :-
Griseofluvin.