Drugs exert their therapeutic effects by interacting with specific biological targets within the body. This interaction is highly selective, akin to a "lock and key" mechanism.

Receptors
Many drugs act by binding to receptors, which are typically large protein molecules (often embedded in cell membranes or located within the cytoplasm/nucleus). Receptors have specific binding sites for natural signaling molecules (ligands) such as hormones or neurotransmitters.

• Agonists: Drugs that bind to a receptor and mimic the action of the natural ligand, thereby activating the receptor and eliciting a biological response. For example, some pain relievers act as opioid receptor agonists.
• Antagonists: Drugs that bind to a receptor but do not activate it. Instead, they block the binding of the natural ligand or agonist, thereby preventing a biological response. For example, beta-blockers act as adrenergic receptor antagonists to lower blood pressure.

Enzymes
Enzymes are biological catalysts (proteins) that facilitate specific biochemical reactions. Drugs can modulate enzyme activity:

• Enzyme Inhibitors: Drugs that bind to an enzyme and reduce or stop its catalytic activity. This can block a disease-causing metabolic pathway.
• Competitive Inhibition: The inhibitor resembles the enzyme's natural substrate and binds to the active site, competing with the substrate. This inhibition can often be overcome by increasing substrate concentration.
• Non-competitive Inhibition: The inhibitor binds to an allosteric site (a site other than the active site), causing a conformational change in the enzyme that reduces or eliminates its ability to bind the substrate or catalyze the reaction. Increasing substrate concentration will not overcome this inhibition. Example: ACE inhibitors (for high blood pressure) block the angiotensin-converting enzyme.
• Enzyme Activators: Drugs that enhance enzyme activity. These are less common but do exist.

Intermolecular Forces in Drug-Target Binding (HL)
The binding of a drug molecule to its target (receptor or enzyme) involves various non-covalent intermolecular forces. These interactions must be specific enough to ensure selectivity and strong enough for the drug to exert its effect.

• Hydrogen Bonding: Occurs between hydrogen atoms covalently bonded to highly electronegative atoms (like O or N) and lone pairs on other electronegative atoms. Crucial for specific recognition and binding.
• Van der Waals Forces (London Dispersion Forces, Dipole-Dipole Interactions): Weak, short-range attractive forces arising from temporary or permanent dipoles. They are significant in cumulatively holding a drug within a binding pocket, especially for hydrophobic regions.
• Ionic Interactions (Electrostatic Interactions): Occur between oppositely charged groups (e.g., protonated amine and deprotonated carboxylate). These are strong and highly specific interactions, often playing a role in initial binding.
• Hydrophobic Interactions: Non-polar parts of the drug and target tend to associate in an aqueous environment to minimize contact with water, driven by entropic factors. These interactions are vital for binding of lipophilic drugs within hydrophobic pockets.
• Covalent Bonds: While most drug-target interactions are non-covalent and reversible, some drugs (e.g., irreversible enzyme inhibitors like aspirin, which acetylates cyclooxygenase) form permanent covalent bonds with their targets. These drugs have very long-lasting effects as the target protein must be resynthesized.