2(3)Hydrolysis

Hydrolysis

is the splitting up of a molecule with water, the –OH group of water becoming part of one molecule and the hydrogen atom becoming part of the other

Hydrolysis

Ester + water → carboxylic acid + alcohol

Esterification

carboxylic acid + alcohol → ester + water

Ester Hydrolysis

Amide hydrolysis

Hydrolysis

Types of Reactions:

Cocaine, Aspirin, Enalapril

Ester Hydrolysis

Amide Hydrolysis

Lidocaine, Procainamide, Indomethacin

Amide Hydrolysis

PHASE II or

CONJUGATION REACTIONS

Convert the Phase I metabolites to more polar and water-soluble products.

methylation and acetylation

do not generally increase water solubility but mainly 2. serve to terminate or attenuate pharmacological activity.

Detoxification

can be regarded as detoxifying

pathways

Glutathione

For Detoxification

Glycine, Cysteine, glutamate

Peptide of Glutathione

N-acetyl cysteine

Cysteine present in

N-acetyl cysteine

Antidote for paracetamol toxicity

N-acetyl cysteine

Precursor of glutathione

Mucolytic agent

N-acetyl cysteine use

Glucuronidation

In neonates and children, this processes are often not developed fully. accumulation of drug leading to toxicity

neonatal hyperbilirubinemia

inability of newborns to conjugate bilirubin with glucuronic acid

gray baby syndrome

inability to metabolize chloramphenicol

Acetylation

For drugs containing Nitrogen

Sulfonamides, Isoniazid,

Hydralazine, Procainamide

Acetylation

● Examples:

Systemic Lupus Erythematosus

❌ enzyme Acetyl transferase

O-glucuronide conjugate

Acetaminophen

In adults major metabolite

O-sulfate conjugate

Acetaminophen

In infants and young chidren (ages 3-9 years)

~ main urinary product

Glycine conjugate

Aspirin

Main metabolite

Salicylic acid

Aspirin

A greater proportion of the drug appears in the urine as

Glucuronidation and sulfation

Paracetamol undergoes

Glutathione

Paracetamol is conjugated with

1. Chemical Structure of Drug

2. Genetic Differences

3. Diet & Environmental Factors

4. Physiologic Stress or Disease

5. Age

6. Gender

7. Drug Interactions

Factors Affecting Drug Metabolism

CYP1A enzyme

Charcoal broiled foods and CRUCIFEROUS vegetables induce

CYP3A

Grapefruit juice inhibit

Enzyme induction

Cigarette smoking

Workers exposed to some pesticides

Excretion

The removal of drugs from the body

▪ A drug or metabolite must be polar or

water-soluble.

Half-Life

The time it takes for one half of the original amount of a drug in the body to be removed.

Half-Life

A measure of the rate at which drugs are removed from the body.