Learning Objective
By the end of this section, students should be able to identify the specific antidotes or treatments for common drug and toxin overdoses, a high-yield topic for USMLE Step 1 pharmacology and toxicology.
Specific Toxin Treatments
| Toxin / Drug | Treatment / Antidote | Notes / Mechanism |
|---|---|---|
| Acetaminophen | N-acetylcysteine | Replenishes glutathione to detoxify NAPQI |
| AChE inhibitors, organophosphates | Atropine > pralidoxime | Atropine blocks muscarinic effects; pralidoxime regenerates AChE |
| Antimuscarinic / Anticholinergic agents | Physostigmine (crosses BBB), supportive care | Controls hyperthermia, reverses CNS symptoms |
| Arsenic | Dimercaprol, succimer | Chelation therapy |
| Benzodiazepines | Flumazenil | Competitive GABA-A receptor antagonist |
| β-blockers | Atropine, glucagon, IV fluids | Glucagon increases cAMP independently of β-receptor |
| Carbon monoxide | 100% O₂, hyperbaric O₂ | Displaces CO from hemoglobin, improves tissue oxygenation |
| Copper | Penicillamine, trientine | Chelation therapy (“3 copper pennies”) |
| Cyanide | Hydroxocobalamin, nitrites + sodium thiosulfate | Binds cyanide → forms non-toxic complex |
| Dabigatran | Idarucizumab | Direct antidote for thrombin inhibitor |
| Digoxin | Digoxin-specific antibody fragments | Binds digoxin, neutralizing its effect |
| Direct factor Xa inhibitors (e.g., apixaban) | Andexanet alfa | Acts as decoy receptor for factor Xa inhibitors |
| Heparin | Protamine sulfate | Binds and neutralizes heparin |
| Iron (Fe) | Deferoxamine, deferasirox, deferiprone | Chelation therapy for iron overload |
| Lead | Penicillamine, calcium disodium EDTA, dimercaprol, succimer | Chelation therapy; succimer preferred in pediatrics |
| Mercury | Dimercaprol, succimer | Chelation therapy |
| Methanol, Ethylene glycol (antifreeze) | Fomepizole > ethanol, dialysis | Inhibits alcohol dehydrogenase; dialysis removes toxin |
| Methemoglobinemia | Methylene blue, Vitamin C | Reduces Fe³⁺ → Fe²⁺ in hemoglobin |
| Methotrexate | Leucovorin | “Rescue” therapy; bypasses DHFR inhibition |
| Opioids | Naloxone | μ-opioid receptor antagonist |
| Salicylates | NaHCO₃, dialysis | Alkalinizes urine to enhance excretion |
| Tricyclic antidepressants (TCAs) | NaHCO₃ | Stabilizes cardiac membranes; prevents arrhythmias |
| Warfarin | Vitamin K (delayed), PCC/FFP (immediate) | Reverses anticoagulation |
Activity
USMLE Step 1 Pearls
- N-acetylcysteine → acetaminophen
- Physostigmine → anticholinergic toxicity (crosses BBB)
- Fomepizole → methanol & ethylene glycol
- Digoxin-specific Fab → digoxin overdose
- NaHCO₃ → salicylates, TCAs
- Andexanet alfa → direct factor Xa inhibitors
- Flumazenil → benzodiazepines (caution: may precipitate seizures in chronic users)
