Pharmacology and Therapeutics
Two lenses: PD and PK
Pharmacodynamics is what the drug does to the body: receptor binding, agonist / partial agonist / inverse agonist behaviour, competitive versus non-competitive antagonism, potency (EC50) versus efficacy (Emax), and the therapeutic index that separates effective from toxic exposure. Pharmacokinetics is what the body does to the drug: absorption and bioavailability (F, first-pass effect), distribution (volume of distribution, protein binding), metabolism (phase I CYP450 oxidation, phase II conjugation), and excretion. Clearance sets the maintenance dose; volume of distribution sets the loading dose.
Kinetics that examiners test
Most drugs follow first-order kinetics, so steady state arrives after roughly 4–5 half-lives, and the plasma level rises by half the plateau with each half-life. Zero-order (saturated) kinetics apply to phenytoin, ethanol, high-dose salicylates and theophylline in overdose: small dose increases cause disproportionate level jumps, and half-life arithmetic fails.
Common traps
- Confusing a loading dose (depends on Vd only) with a maintenance dose (depends on clearance).
- Forgetting enzyme inducers (rifampin, carbamazepine, phenytoin, St John's wort) lower CYP3A4 substrate levels, while inhibitors (clarithromycin, ketoconazole, grapefruit) raise them.
- Overlooking prodrugs requiring activation, e.g. clopidogrel via CYP2C19 - poor metabolisers get less antiplatelet effect.
- Missing disease-state changes: renal impairment accumulates renally cleared drugs; cirrhosis raises free fraction of highly bound drugs.
Rule of thumb with worked example
Loading dose = (Vd × target concentration) / F. For Vd 50 L, target 20 mg/L, F = 1: 50 × 20 ÷ 1 = 1000 mg. Maintenance = CL × target concentration × interval. Always sanity-check units before calculating.