Pharmacokinetics and Toxicokinetics
This domain tests whether you can predict how a concentration changes over time, and use that prediction to choose an intervention. In overdose the assumptions that hold at therapeutic doses - linearity, complete and rapid absorption, constant clearance - frequently fail, and the exam rewards candidates who notice when a calculation is being applied outside its assumptions.
Parameters that matter
- Volume of distribution: Vd = amount in body ÷ plasma concentration. It is a proportionality constant, not an anatomical space. Values above roughly 1 L/kg imply tissue sequestration and predict poor extracorporeal removal.
- Clearance: CL = dose/AUC, and t½ = 0.693 × Vd/CL. A long half-life may reflect a very large Vd rather than slow metabolism, which is why half-life alone must not dictate dialysis decisions.
- First-order elimination removes a constant fraction per unit time. Zero-order (saturable) elimination removes a constant amount, so half-life lengthens as concentration rises - ethanol, phenytoin, and salicylate at high doses are the classic examples.
Absorption in the overdose setting
Delayed gastric emptying, pharmacobezoars, sustained-release formulations and anticholinergic co-ingestants prolong absorption, so a level drawn at two hours may not be the peak. Enterohepatic recirculation can produce secondary peaks and a late rise in concentration.
Extracorporeal clearance
Dialysis adds to intrinsic clearance: CL_total = CL_body + CL_HD. Only unbound drug in plasma is removed, so a drug that is highly protein-bound or has a huge Vd is a poor dialysis candidate regardless of how toxic it is.
Worked example. A 70 kg patient ingests 20 g of a drug; the initial concentration is 200 mg/L. Vd = 20,000 mg ÷ 200 mg/L = 100 L (1.4 L/kg). Intermittent haemodialysis achieves a clearance of 100 mL/min for 4 hours, so the cleared volume is 0.1 L/min × 240 min = 24 L, removing roughly 24 L × 200 mg/L ≈ 4.8 g, or about a quarter of the dose - and less in practice as the concentration falls. Because the drug is largely extravascular, dialysis is an adjunct, not a definitive treatment: supportive care and repeated dosing matter more.
Traps that cost marks
- Confusing Vd with plasma volume, or assuming a large Vd means the drug is not toxic.
- Calculating half-life from a single level, or ignoring that half-life changes when kinetics saturate.
- Recommending haemodialysis for a highly protein-bound or high-Vd drug.
- Forgetting that protein binding, not molecular weight alone, limits removal.