General Principles of Toxicology: Toxicokinetics, Risk Assessment, Decontamination, and Supportive Care
Toxicokinetics drives decisions
Volume of distribution (Vd) predicts whether extracorporeal removal can work. Large-Vd, highly protein-bound toxins (digoxin, tricyclics, verapamil, chloroquine) are not meaningfully removed by hemodialysis, whereas small-Vd, poorly bound toxins (lithium, methanol, ethylene glycol, salicylate, theophylline) are. Elimination order matters too: first-order elimination removes a constant fraction per unit time with a stable half-life, while zero-order (saturable, Michaelis–Menten) elimination - ethanol, high-dose salicylate, phenytoin - removes a fixed amount per time, so half-life lengthens as concentration rises and small dose increments cause disproportionate level increases.
Risk assessment
Regulatory toxicology uses NOAEL/LOAEL, benchmark dose, reference dose (RfD), and uncertainty factors (typically 10 for animal-to-human extrapolation and 10 for human variability). LD50 is a crude potency index, not a human threshold. Genotoxic carcinogens are modeled with low-dose linear extrapolation, whereas non-genotoxic effects generally assume a threshold.
Decontamination and supportive care
Airway, breathing, circulation, and treatment of seizures, hyperthermia, and hypoglycemia always precede decontamination. Activated charcoal binds many drugs but is contraindicated for caustics, hydrocarbons with aspiration risk, metals, alcohols, and an unprotected airway. Whole-bowel irrigation suits sustained-release products and body packers. Skin decontamination with soap and water matters for organophosphates and corrosives.
Rule of thumb
When the anion gap, osmolar gap, or reported level does not fit the clinical picture, question the timing and the assay before you question the patient.
Worked example
Lithium toxicity (Vd ~0.6–1 L/kg, minimal protein binding) with renal failure is a dialysis candidate; a tricyclic overdose with the same acidosis is not - treat it with sodium bicarbonate.