Pharmacology: kinetics you can compute, mechanisms you can name
Pharmacology items split into pharmacokinetics, which is numerical and therefore highly scorable, and pharmacodynamics plus systems drugs, which is recall-driven. The examiner's favourite trap is giving you everything needed for a calculation and watching units or bioavailability get dropped.
Core rules
- Volume of distribution = dose / plasma concentration. Loading dose = (Vd x target concentration) / bioavailability.
- Clearance = rate of elimination / plasma concentration; maintenance dose = (clearance x steady-state concentration) / bioavailability.
- Half-life determines time to steady state (about four to five half-lives) but not the size of the steady-state level.
- First-order kinetics means a constant fraction is eliminated per unit time; zero-order means a constant amount, as with ethanol, high-dose aspirin and phenytoin at saturation.
- Inducers (rifampicin, carbamazepine, phenytoin, chronic alcohol) lower levels of co-administered drugs; inhibitors (erythromycin, ketoconazole, cimetidine, grapefruit) raise them.
Worked example
A patient needs a target plasma concentration of 20 mg/L of a drug with a volume of distribution of 40 L and bioavailability 1.0. Loading dose = (40 x 20)/1 = 800 mg. If the same drug has clearance 4 L/h and you want to keep 20 mg/L, maintenance = (4 x 20)/1 = 80 mg/h. Note what each parameter does: doubling Vd doubles the loading dose but leaves the maintenance rate unchanged, and doubling clearance halves the maintenance rate but leaves the loading dose unchanged.
Traps that cost marks
- Forgetting to divide by bioavailability when the drug is given orally.
- Confusing half-life with duration of action; a drug can have a short half-life and long effect if it binds irreversibly.
- Antidote pairs asked as a set: organophosphate and atropine plus pralidoxime, opioid and naloxone, paracetamol and N-acetylcysteine, warfarin and vitamin K.
- Beta-blockers are not interchangeable: cardioselectivity and intrinsic sympathomimetic activity differ.