Pharmacology: Pharmacokinetics, Autonomics and Therapeutics
Pharmacology questions combine numerical pharmacokinetics with clinical drug choice and adverse effects. Expect loading-dose calculations, half-life reasoning, autonomic receptor pharmacology, antimicrobial spectrum and toxicology antidotes.
Core rules
- Zero-order kinetics: phenytoin, ethanol, high-dose salicylate and theophylline. Steady state is reached after four to five half-lives.
- Cytochrome inducers include rifampicin, phenytoin, carbamazepine and phenobarbitone; inhibitors include macrolides, azoles, valproate and cimetidine.
- Loading dose = (Vd x target concentration)/bioavailability; maintenance dose = clearance x target concentration.
- Organophosphate poisoning: atropine titrated to drying of secretions, plus pralidoxime before enzyme ageing; avoid succinylcholine because pseudocholinesterase is inhibited.
Worked example
A 70 kg patient needs a drug with Vd 0.5 L/kg, target concentration 20 mg/L, clearance 3 L/h and complete intravenous bioavailability. Vd = 0.5 x 70 = 35 L. Loading dose = 35 L x 20 mg/L = 700 mg. Maintenance infusion = 3 L/h x 20 mg/L = 60 mg/h. Had oral bioavailability been 0.5, the loading dose would need to double to 1400 mg to achieve the same concentration.
Traps
- Mixing up inducers and inhibitors under time pressure.
- Using atropine as the sole endpoint in organophosphate poisoning without checking for adequate drying of secretions.
- Forgetting that rifampicin reduces the effect of oral contraceptives and many antiretrovirals.