Pharmacodynamics Lecture Notes

Definition

• Pharmacodynamics: Study of what a drug does to the body (opposite of pharmacokinetics).
• Drugs interact with cell receptors to create signals, leading to biological effects.

Types of Receptors

1. Ligand-Gated Ion Channels

   • Have ligand binding sites.
   • Ligand binds → channel opens briefly → ions (Na+, K+, Cl-, Ca2+) pass through.

2. G Protein-Coupled Receptors (GPCRs)

   • Also known as seven-transmembrane receptors.
   • Three subunits: alpha, beta, gamma (together form G protein).
   • Inactive alpha subunit has GDP; becomes active with GTP when ligand binds.
   • Types of G Proteins:
     • Gs: Stimulates adenylyl cyclase → increases cAMP (second messenger).
     • Gi: Inhibits adenylyl cyclase → decreases cAMP.
     • Gq: Activates phospholipase C (PLC) → produces DAG and IP3.
   • Capable of signal amplification.

3. Enzyme-Linked Receptors

   • Have extracellular ligand binding site.
   • Often tyrosine kinase type.
   • Ligand binding leads to dimerization and auto-phosphorylation.

4. Intracellular Receptors

   • Located inside the cell; ligand must cross membrane.
   • Ligand-receptor complex moves to nucleus to affect gene expression.

Receptor Life Cycle

• DNA codes for receptor proteins which embed in cell membrane.
• Downregulation: Reduces receptor number and sensitivity to signals.
• Upregulation: Increases receptor number and sensitivity.

Drug-Receptor Interaction

• EC50: Concentration producing 50% of maximal effect; indicates potency.
• Emax: Maximum efficacy; all receptors occupied.

Drug Activity Types

• Full Agonist: Produces maximal effect.
• Partial Agonist: Cannot produce maximal effect even if all receptors are occupied.
• Inverse Agonist: Stabilizes inactive receptor form; reduces basal activity.
• Antagonist: Binds receptor but blocks action.
  • Competitive Antagonist: Shifts agonist dose-response curve right; affects potency.
  • Non-Competitive Antagonist: Covalently binds, reducing efficacy (Emax) without affecting potency (EC50).
  • Allosteric Antagonist: Binds different site inducing conformational change; reduces Emax without affecting EC50.

Therapeutic Index (TI)

• Measures drug safety: ratio of toxic dose (TD50) to effective dose (ED50).
• Graph shows therapeutic and toxic responses.

• Note: Therapeutic index provides safety range for drug dosages to avoid toxicity while achieving therapeutic effect.