PH1.7-9 | PH1.7-9 | Pharmacodynamics, Prototype Drug Effects and Rational Combinations — SDL Guide — Summary & Reflection

KEY TAKEAWAYS

Pharmacodynamics is what drugs do to the body — mediated primarily through receptor binding but also via enzyme inhibition, ion channel modulation, transporter blockade, and physicochemical mechanisms.

Dose-response parameters: Emax = maximal efficacy (ceiling effect); EC50 = potency (lower = more potent); therapeutic index (TI = TD50/ED50) quantifies the safety margin — narrow TI drugs (digoxin, phenytoin, lithium) require TDM.

Agonist-antagonist spectrum: full agonist (maximum Emax); partial agonist (submaximal Emax, high affinity — can displace full agonists); inverse agonist (opposite effect to agonist); competitive reversible antagonist (rightward curve shift, Emax preserved — e.g., naloxone); competitive irreversible / non-competitive antagonist (reduced Emax).

Non-receptor mechanisms: irreversible enzyme inhibition (aspirin → COX — 7-10d antiplatelet effect, not PK t½); reversible enzyme inhibition (ACE inhibitors); ion channel block (local anaesthetics Na+; CCBs Ca2+); transporter inhibition (SSRIs, SERT).

Prototype drugs: morphine (full mu-agonist), atropine (competitive muscarinic antagonist), aspirin (irreversible COX inhibitor), adrenaline (mixed alpha/beta agonist), propranolol (non-selective beta-antagonist).

Drug combinations: synergism (additive or potentiation — e.g., co-trimoxazole rational; alcohol + BZD hazardous); pharmacological antagonism (same receptor — naloxone/morphine); chemical antagonism (protamine/heparin); physiological antagonism (different receptors — adrenaline in anaphylaxis).

REFLECT

Consider a patient on long-term aspirin for secondary stroke prevention who also regularly uses ibuprofen for arthritis pain. From what you now know about aspirin's irreversible COX inhibition versus ibuprofen's reversible inhibition, what pharmacodynamic interaction would you predict? What would you counsel this patient? Write two or three sentences applying the concept of competitive reversible vs irreversible inhibition to this real prescribing scenario.