Pharmacodynamics: Receptors, Agonists & Dose-Response in Detail

If pharmacokinetics is “what the body does to the drug,” pharmacodynamics is “what the drug does to the body.” It explains how a drug binds its target and how the response changes with dose — and the dose–response curve below is where it all comes together.

Drug targets & receptor families

• Ligand-gated ion channels — fastest (milliseconds): nicotinic ACh, GABA-A, glutamate.
• G-protein coupled receptors (GPCRs) — the largest family; act via second messengers (cAMP, IP₃/DAG, Ca²⁺): adrenergic, muscarinic, opioid, dopamine.
• Enzyme-linked (kinase) receptors — minutes to hours: insulin, growth factors.
• Nuclear (intracellular) receptors — slowest (hours–days), alter gene transcription: steroids, thyroid hormone, vitamin D.

Agonists, antagonists & everything between

• Full agonist — binds and produces the maximal response (affinity + full efficacy).
• Partial agonist — submaximal response even at full occupancy (buprenorphine, pindolol); acts as an antagonist in the presence of a full agonist.
• Antagonist — affinity but zero efficacy.
  • Competitive (reversible): surmountable — shifts the curve right, same maximum (naloxone, propranolol).
  • Non-competitive (irreversible / allosteric): insurmountable — lowers the maximum (phenoxybenzamine).
• Inverse agonist — produces the opposite effect to the agonist on a constitutively active receptor.

Affinity vs efficacy (don’t confuse with potency)

• Affinity — how tightly a drug binds (governs the dose needed).
• Efficacy / intrinsic activity — the ability to produce a response once bound (governs the maximum achievable).
• Potency = dose required for a given effect (position on the x-axis); efficacy = the maximal effect (height of the curve). A more potent drug is not necessarily more effective.

Graded vs quantal responses

• Graded: a continuous increase with dose in one individual — used to compare potency & efficacy.
• Quantal (all-or-none): measured across a population — gives ED50, TD50, and LD50.

The safety margin

Therapeutic index (TI) = TD50 / ED50. A high TI means a wide margin; low-TI drugs (warfarin, digoxin, lithium, phenytoin, theophylline) need therapeutic drug monitoring.

Receptor regulation

• Tolerance / tachyphylaxis — diminishing response (down-regulation, desensitisation).
• Up-regulation — chronic antagonism increases receptor number, causing rebound on withdrawal (β-blocker withdrawal → rebound tachycardia).
• Spare receptors — a maximal response with only partial occupancy.

Exam tip: Competitive antagonist → curve shifts right, maximum unchanged (surmountable). Non-competitive → maximum falls (insurmountable). And remember: potency ≠ efficacy — a classic trap.

Pharmacokinetics gets the drug to the receptor; pharmacodynamics decides what happens next. Together they explain dose, timing, interactions, and toxicity across all of pharmacology.