OIA1013 (TERMS) DRUG METABOLISM

Drug Elimination

Irreversible removal of drug from the body.

Excretion

Removal of intact drug from the body.

Biotransformation

Chemical conversion of drug to metabolite.

First-pass effect

Metabolism in liver reduces active drug availability.

Phase I Metabolism

Involves oxidation, reduction, or hydrolysis reactions.

Phase II Metabolism

Conjugation of metabolites to enhance water solubility.

Cytochrome P450

Key enzyme family in drug metabolism.

CYP450 Enzymes

Over 50 enzymes metabolizing 90% of drugs.

Hydrophilic Molecules

More polar molecules for easier elimination.

Prodrugs

Inactive drugs converted to active forms post-metabolism.

Oxidation

Addition of oxygen or removal of hydrogen.

Reduction

Removal of oxygen or addition of hydrogen.

Hydrolysis

Addition of water to break down compounds.

Enzyme Induction

Increases P450 enzyme activity and drug metabolism.

Enzyme Inhibition

Decreases P450 enzyme activity and increases drug effects.

Grapefruit Juice

Causes suicide inhibition of CYP3A4 enzymes.

Renal Excretion

Primary route for drug elimination via urine.

Clinical Relevance

Understanding metabolism impacts drug efficacy and safety.

Liver Activity

Primary site for drug metabolism (100% activity).

Tissue Distribution

Metabolism occurs in liver, lungs, kidneys, etc.

NAPQI

Toxic metabolite of paracetamol causing liver damage.

Glucuronidation

Phase II process making drugs more water-soluble.

Gray Baby Syndrome

Toxicity in neonates due to glucuronyl transferase deficiency.

Active Metabolite

Converted active drug prolonging therapeutic effects.

Inactive Metabolite

Converted active drug resulting in termination of action.

Microsomal Enzymes

Located in endoplasmic reticulum, involved in metabolism.

Non-microsomal Enzymes

Present outside endoplasmic reticulum, catalyze various reactions.

Factors Affecting Metabolism

Include enzyme induction, inhibition, and genetic factors.