The document discusses biotransformation, which is the chemical alteration of drugs in the body. The body treats drugs as foreign substances and converts them into more polar, water soluble compounds through biotransformation so they can be excreted through the kidneys. Biotransformation occurs primarily in the liver and involves two phases - phase I reactions change the drug through processes like oxidation and phase II involves conjugating the drug to make it inactive so it can be excreted. Factors like other drugs, food, and an individual's characteristics can impact the biotransformation of drugs through inhibition or induction of the enzymes involved.
5. Introduction
Body treats most drugs as foreign substances and tries to
inactivate them and eliminate them.
They convert the drugs into more polar , water soluble
compounds so that they can be easily excreted through the
kidneys.
6. Biotransformation of drugs
Chemical alteration of the drug in the body
Drugs may be
Excreted unchanged
Metabolized by enzymes
Spontaneously changed
7. CONSEQUENCES
Inactivation
Paracetamol
Lidocaine
Propranolol
Active metabolite from an active drug
Codeine, Morphine
Activation of an inactive drug
Prodrug :- Initially inactive converted in body to active form
Advantages – Stable, better bioavailability, less toxic
Levodopa Dopamine
9. Types of biotransformation reaction
Phase I
Non synthetic/Degradative
changes drugs and creates site
for phase II
Metabolite:- Active/Inactive
Types:-
Oxidation
Reduction
Hydrolysis
Cyclization
Decyclization
Phase II
Synthetic/ Conjugation
group added to existing (or phase I
formed) conjugation site
Metabolite:- Inactive
Types:-
Glucuronide conjugation
Sulphate conjugation
Glutathione conjugation
Glycine conjugation
Methylation, Acetylation
10. ENZYMES FOR BIOTRANSFORMATION
Microsomal enzymes
Present in smooth surfaced ER of liver
Mixed functn enzymes & cyt P-450
Involved in phase I reactions & glucuronide
conjugation(Phase II)
Non-microsomal enzymes
Present in plasma, cytoplasm,mitochondria
Involved in all phase II reactions except
glucuronide
12. Inhibitors and inducers of microsomal enzymes
INHIBITORS
Inhibits Cytochrome P450-> Inhibits metabolism of certain
drugs
Eg. Cimetidine, ketoconazole, ciprofloxacin
INDUCERS
Synthesis of microsomal enzymes enhanced by certain drugs
-> Speeds up metabolism of drugs
Eg: barbiturates, carbamazepine , Alcohol, Cigarette smoke.
13. Factors affecting biotransformation
Race (CYP2C9; warfarin (bleeding) phenytoin (ataxia) Losartan
(less cleared but less activated as well); also fast and slow
isoniazid acetylators
Age (reduced in aged patients & children)
Sex (women slower ethanol metabolizers)
Species
Clinical or physiological condition
Other drug administration (induction or inhibition)
Food
charcoal grill ++CYP1A
grapefruit juice --CYP3A
First-pass metabolism
14. Summary
Definition of biotransformation
Primary site of metabolism
Prodrug
Types of biotransformation reactions
First pass metabolism
Enzyme inducers
Hoffman’s elimination