Organic Isomers, Drug-Receptor Interactions, and Metabolism: Key Concepts for Pharmacology

Isomers

Compounds with the same formula but different structures

Structural isomers

Same formula, atoms connected differently

Tautomers

Interconvert by hydrogen shift + double bond shift

Stereoisomers

Same connectivity, different 3D arrangement

Conformational isomers

Rotation around single bonds

Configurational isomers

Cannot interconvert without breaking bonds

Enantiomers

Mirror images, non-superimposable

Diastereomers

Stereoisomers that are not mirror images

Optical activity

Ability to rotate plane-polarized light

Max # stereoisomers

2ⁿ (n = # of chiral centers)

Three-point attachment concept

Explains why enantiomers interact differently with receptors

Receptor

Macromolecule drug binds to for response

Examples of receptors

Proteins, enzymes, transport proteins, structural proteins, nucleic acids

Complementarity

Shape, size, polarity, charges match between drug & receptor

Forces involved

Van der Waals, dipole-dipole, hydrogen bonding, ionic, hydrophobic, covalent

Salt bridge

Ionic bond often stabilized by cations/anions

Hydrophobic effect

Entropy-driven exclusion of water increases binding

Covalent bonds

Rare but irreversible binding (e.g., phenoxybenzamine)

Drug metabolism

Biochemical modification to aid elimination

Phase I reactions

Functionalization (oxidation, reduction, hydrolysis)

Phase II reactions

Conjugation (glucuronidation, sulfation, etc.)

First-pass effect

Reduced drug bioavailability due to liver metabolism

Enzyme system

Cytochrome P450 (major oxidizer)

Enzyme induction

Increases metabolism (shorter drug action)

Enzyme inhibition

Decreases metabolism (longer drug action, possible toxicity)