Pharmacology and Toxicology: Kinetics, Dynamics and Antidotes
What the domain tests
This section checks whether you can reason from pharmacokinetic parameters and receptor pharmacology to bedside decisions, and whether you know the antidotes and toxidromes. Numerical items on half-life, volume of distribution and loading dose are common, as are classification items on autonomic, CNS, cardiovascular and antimicrobial drugs.
Core rules to hold
- Kinetic relationships: t½ = 0.693 × Vd / CL; loading dose = Vd × target concentration; maintenance rate = CL × target concentration; bioavailability matters for the oral route because of first-pass metabolism.
- Order of kinetics: first-order for most drugs; zero-order (saturated) for phenytoin, ethanol and high-dose aspirin, where a constant amount is eliminated per unit time.
- Receptor families: G-protein-coupled, ligand-gated ion channels, enzyme-linked (insulin receptor tyrosine kinase) and nuclear receptors.
- Antagonism: competitive antagonism shifts the dose–response curve right with unchanged maximum; non-competitive depression lowers the maximum.
- Antidotes: organophosphate - atropine plus pralidoxime; paracetamol - N-acetylcysteine; methanol/ethylene glycol - fomepizole; opioid - naloxone; benzodiazepine - flumazenil; warfarin - vitamin K; cyanide - sodium nitrite then sodium thiosulphate.
Worked example
A drug has Vd 40 L and a target plasma concentration of 2 mg/L. Loading dose = 40 × 2 = 80 mg. If clearance is 4 L/h, the maintenance infusion is 4 × 2 = 8 mg/h. With t½ = 0.693 × 40/4 ≈ 6.9 h, a steady state is reached in roughly five half-lives, about 35 hours.
Traps that cost marks
Giving flumazenil in a mixed tricyclic–benzodiazepine overdose, where it can precipitate seizures; assuming phenytoin follows first-order kinetics at high doses; forgetting that theophylline, digoxin, lithium and warfarin have narrow therapeutic indices requiring monitoring.