Pharmaceutical Agents: Antidotes, Toxidromes, and Overdose Management
High-yield antidote pairs
Acetaminophen: NAPQI accumulates when glutathione is depleted; N-acetylcysteine replenishes precursors. Apply the Rumack–Matthew nomogram only to single acute ingestions timed at 4 hours or later; for repeated supratherapeutic ingestion or unknown timing, treat empirically using level plus transaminases. Salicylates cause mixed respiratory alkalosis and anion-gap metabolic acidosis with tinnitus and altered mentation; treat with sodium bicarbonate for urinary alkalinization (urine pH 7.5–8.0) and hemodialysis for severe acidosis, CNS toxicity, renal failure, or levels above the dialysis threshold.
Cardiovascular drugs
Beta-blockers and calcium-channel blockers cause bradycardia, hypotension, and conduction delay. Escalate from fluids and calcium (for CCB) to glucagon, high-dose insulin euglycemia therapy, vasopressors, and lipid emulsion for lipophilic agents. Digoxin toxicity produces hyperkalemia, bradyarrhythmias, and visual disturbances; give Fab fragments and avoid calcium. Sulfonylureas cause prolonged hypoglycemia: dextrose plus octreotide.
Sodium-channel and CNS agents
Tricyclic antidepressants widen the QRS and cause hypotension and seizures; give sodium bicarbonate 1–2 mEq/kg for QRS >100 ms and avoid flumazenil and physostigmine in these patients. Serotonin syndrome (clonus, hyperreflexia, hyperthermia) versus neuroleptic malignant syndrome (lead-pipe rigidity, hyporeflexia, onset over hours to days) is a classic distinction. Metformin causes lactic acidosis managed with dialysis; valproate-associated carnitine depletion is treated with L-carnitine; theophylline causes tachycardia, hypokalemia, and seizures treated with benzodiazepines and possibly hemodialysis.
Rule of thumb
Ask what was prescribed, what was on the nightstand, and what the pill count says - the ingested dose, not the first level, triages the unstable patient.
Worked example
QRS 120 ms with hypotension after an overdose: 1–2 mEq/kg sodium bicarbonate boluses, repeated until the QRS narrows and pressure improves.