Pharmacology and Toxicology: Receptors, Kinetics and Antidotes
Pharmacology and Toxicology tests receptor theory, pharmacokinetics, systemic pharmacology and poisoning management. Numerical pharmacokinetics and antidote-matching items are common.
Core rules
- Receptors: ligand-gated ion channels (nicotinic), G-protein coupled (β-adrenergic, muscarinic), kinase-linked (insulin) and nuclear (steroid, thyroid).
- Dose–response: ED50, LD50, therapeutic index = LD50/ED50; potency versus efficacy; competitive antagonism shifts the curve right without reducing maximum response.
- Pharmacokinetics: Vd = Dose/C0; t½ = 0.693/k; CL = k × Vd; Css = infusion rate/CL; loading dose = Vd × target concentration.
- Non-linear kinetics: phenytoin, ethanol and high-dose salicylate show saturation, so small dose increases produce large level rises.
- Antidotes: atropine plus pralidoxime for organophosphate poisoning; N-acetylcysteine for paracetamol; naloxone for opioids; desferrioxamine for iron; dimercaprol for arsenic; penicillamine for copper; methylene blue for methaemoglobinaemia.
Worked example
A 500 mg intravenous dose gives an initial concentration of 25 mg/L, so Vd = 500/25 = 20 L. If k = 0.1 h⁻¹, t½ = 0.693/0.1 = 6.93 h and CL = 0.1 × 20 = 2 L/h. An infusion of 20 mg/h therefore reaches Css = 20/2 = 10 mg/L. To reach 10 mg/L immediately, a loading dose of 20 L × 10 mg/L = 200 mg is required.
Traps
Vd is an apparent volume, not an anatomical one; first-order elimination does not apply to phenytoin at therapeutic doses; rifampicin induces CYP enzymes and lowers drug levels, while erythromycin and ketoconazole inhibit them; and atropine treats muscarinic effects of organophosphate poisoning but not the neuromuscular blockade.