[PHARM-01] General Pharmacology: Receptor Theory, Dose–Response Relationships & Signal Transduction
PHARM-01 • 2. PharmacologyLearning Objectives
Differentiate affinity, intrinsic activity (efficacy), potency, and therapeutic index using quantitative log dose–response curves.; Classify the 4 primary receptor superfamilies (Ligand-gated ion channels, GPCRs, Enzyme-linked RTKs, Nuclear receptors) with time-scales and canonical second messengers.; Compare competitive, irreversible/non-competitive, physiological, and chemical antagonism with clinical antidote pairs.; Explain receptor up-regulation, down-regulation, tachyphylaxis, and spare receptors in clinical pharmacotherapy.
Chapter Overview & Core Explanation
Drugs work mostly by binding to specialized molecular locks called receptors on or inside cells. Affinity describes how tightly a drug fits the lock, while intrinsic activity (efficacy) describes whether turning the key actually opens the door (agonism) or blocks the keyhole so the natural messenger cannot enter (antagonism).
Key Exam & Clinical Takeaways
- Potency (EC50) determines the milligram dose needed, whereas efficacy (E_max) determines clinical ceiling effectiveness—clinicians prioritize efficacy and safety margin over raw potency.
- Abrupt withdrawal of chronic β-blockers ([3.11] Metoprolol, [3.10] Atenolol) causes rebound angina/tachycardia due to homologous receptor up-regulation.
- Continuous exposure to β2-agonists ([4.1] Salbutamol) or nitrates ([3.28] Nitroglycerin) induces β-arrestin-mediated receptor desensitization or thiol depletion (tachyphylaxis), requiring nitrate-free intervals.