Pharmacodynamics: Mechanisms of Drug Action covers pharmacodynamics — mechanisms of drug action for INI CET (AIIMS PG).
Pharmacodynamics (PD): What the drug does to the body — mechanism of action, dose-response, toxicity.
Mechanisms of Drug Action:
- Receptor-mediated (most common): Drug binds to a specific cellular receptor
- Agonists: Bind and activate receptor (full agonist = maximal response; partial agonist = submaximal)
- Antagonists: Bind but do NOT activate receptor
- Competitive (reversible): Competes with agonist at same binding site; surmountable with high agonist concentration
- Non-competitive (irreversible): Binds at different site or irreversibly; insurmounable
- Inverse agonists: Bind to same receptor as agonists but produce opposite effect (e.g., inverse agonist at GABA receptor → anxiogenic)
- Enzyme inhibition: Direct enzyme inhibition (e.g., ACE inhibitors, cholinesterase inhibitors)
- Ion channel modulation: Open or close ion channels (e.g., calcium channel blockers, sodium channel blockers)
- Direct receptor antagonism: Receptor blockade without activation
- Chemical antagonism: Direct chemical interaction (e.g., protamine reverses heparin)
Receptor Types:
| Type | Structure | Example |
|---|---|---|
| GPCR (G-protein coupled) | 7TM (7-transmembrane) | Adrenoceptors, muscarinic receptors, histamine receptors |
| Ligand-gated ion channels | Multisubunit (ion channel) | Nicotinic AChR, GABA-A, NMDA, serotonin 5-HT₃ |
| Tyrosine kinase receptors | Single TM, intracellular kinase | Insulin receptor, growth factor receptors |
| Nuclear receptors | Intracellular/cytosolic | Steroid receptors (cortisol, thyroid hormone), PPAR |
| Voltage-gated channels | Multisubunit pore | Na⁺, K⁺, Ca²⁺ channels |
Dose-Response Relationship:
- Graded dose-response: Effect vs dose on individual
- EC₅₀: Dose producing 50% of maximal effect (measure of POTENCY)
- E_max: Maximum achievable effect (measure of EFFICACY)
- Therapeutic index (TI): LD₅₀/ED₅₀ (or TD₅₀/ED₅₀) — higher TI = safer drug
- Warfarin TI ~2; Digoxin TI ~2; Morphine TI ~70
Quantal Dose-Response (population):
- ED₅₀: Dose effective in 50% of population
- TD₅₀: Toxic dose in 50% of population
- LD₅₀: Lethal dose in 50% of population
- Therapeutic Window: Range between minimum effective concentration and minimum toxic concentration
Receptor Regulation:
- Desensitization/Tolerance: Prolonged agonist exposure → reduced receptor responsiveness (downregulation)
- Tachyphylaxis: Rapid tolerance (e.g., indirect-acting sympathomimetics like tyramine — depletes norepinephrine stores)
- Upregulation: Chronic antagonist use → increased receptor density → supersensitivity on withdrawal
⚡ Exam Tip for INI CET (AIIMS PG): Potency (EC₅₀) vs Efficacy (E_max) — a drug can be potent (low EC₅₀) but have lower efficacy than another drug. Morphine has higher efficacy than codeine but both are opioids.