Pharmacology
Drug antidote
| Drug/Toxin | Antidote | Mechanism | Key Points |
|---|---|---|---|
| Opioids (heroin, morphine, fentanyl, methadone) | Naloxone | Competitive opioid receptor antagonist | IV dose 0.04-4 mg; onset <2 min IV; duration 20 min-2 hrs (shorter than most opioids - re-dosing often needed). Intranasal 4 mg spray is widely used. |
| Benzodiazepines | Flumazenil | GABA-A receptor competitive antagonist | Short duration; may precipitate seizures in chronic users or mixed TCA/BZD overdose - use with caution |
| Barbiturates | Supportive + urinary alkalinization (NaHCO3) for phenobarbital | Enhances renal elimination | No direct antidote; alkalinizing urine to pH 7.5-8.0 increases phenobarbital excretion |
| Drug/Toxin | Antidote | Mechanism | Key Points |
|---|---|---|---|
| Organophosphates / nerve agents (sarin, VX, insecticides) | Atropine + Pralidoxime (2-PAM) | Atropine: muscarinic receptor antagonist. 2-PAM: regenerates acetylcholinesterase | Atropine 2 mg IV, doubled every 5 min until secretions dry. Dose may reach 200-500 mg in 1st hour. 2-PAM: 30 mg/kg IV bolus then 8-10 mg/kg/hr infusion. Atropine does NOT reverse nicotinic (skeletal muscle) effects |
| Carbamates | Atropine (2-PAM controversial) | Same as above | Pralidoxime less useful since carbamate-AChE binding spontaneously reverses |
| Anticholinergic toxidrome (atropine, antihistamines, TCAs) | Physostigmine | Reversible AChE inhibitor; crosses BBB | Used in antimuscarinic poisoning; 30-39% of patients need re-dosing within 5.5 hrs |
| Drug/Toxin | Antidote | Mechanism | Key Points |
|---|---|---|---|
| Digoxin | Digoxin-specific Fab antibody fragments | Binds and inactivates digoxin | Dose based on serum level or estimated ingestion. Reverses toxicity within 30-60 min |
| Beta-blockers | Glucagon, high-dose insulin (HIE), IV lipid emulsion | Glucagon activates adenylyl cyclase bypassing beta receptors; insulin improves myocardial glucose uptake | High-dose insulin 1 unit/kg bolus + infusion is now preferred over glucagon |
| Calcium channel blockers | Calcium, high-dose insulin (HIE), IV lipid emulsion | Calcium overcomes blockade; insulin as above | CaCl2 or Ca gluconate; HIE is cornerstone of severe CCB overdose |
| TCAs / sodium channel blockers (cocaine, quinidine, thioridazine) | Sodium bicarbonate | Alkalinization + sodium loading reverses Na-channel blockade | Target serum pH 7.50-7.55; given as 1-2 mEq/kg bolus; monitors QRS narrowing |
| Warfarin / anticoagulants | Vitamin K1, Fresh Frozen Plasma, PCC | Restores clotting factor synthesis | Vitamin K1 (phytonadione) is specific antidote; FFP/PCC for emergent reversal |
| Heparin | Protamine sulfate | Binds and neutralizes heparin | 1 mg protamine per 100 units heparin; risk of anaphylaxis |
| Drug/Toxin | Antidote | Mechanism | Key Points |
|---|---|---|---|
| Acetaminophen (paracetamol) | N-acetylcysteine (NAC) | Replenishes glutathione; direct sulfhydryl donor; detoxifies NAPQI | Most effective within 8 hrs of ingestion. IV or oral. Rumack-Matthew nomogram guides antidote use. Hemodialysis not routinely used since NAC is highly effective |
| Salicylates | Sodium bicarbonate (urinary alkalinization) + dialysis if severe | Traps ionized salicylate in urine; prevents CNS penetration | Target urine pH 7.5-8.0; target serum pH 7.50-7.55. Treat as acute medical emergency |
| Methanol / Ethylene glycol | Fomepizole (4-MP) or Ethanol + Folic acid / Leucovorin (methanol); Pyridoxine (ethylene glycol) | Competitively inhibits alcohol dehydrogenase, preventing formation of toxic metabolites | Fomepizole preferred; pyridoxine 500 mg IV theoretically enhances elimination of ethylene glycol metabolites |
| Toxin | Antidote | Route | Treatment Endpoint |
|---|---|---|---|
| Lead | Succimer (DMSA), EDTA, DMPS | Oral (succimer); IV (EDTA) | BLL <70 µg/dL; resolution of encephalopathy |
| Arsenic | Succimer (DMSA), BAL (Dimercaprol) | Oral / IM | 24-hr urine arsenic <50 µg/L |
| Mercury | Succimer, DMPS, BAL | Oral / IM | 24-hr urine mercury <20 µg/L |
| Iron | Deferoxamine | IV infusion | Resolution of toxicity, urine clears from "vin rose" color |
| Copper (Wilson's disease) | Penicillamine, Trientine, Zinc | Oral | Normalize copper levels |
| Cyanide | Hydroxocobalamin or Sodium nitrite + Sodium thiosulfate | IV | Hydroxocobalamin is now first-line (safer); thiosulfate donates sulfur for rhodanese reaction |
| Drug/Toxin | Antidote | Notes |
|---|---|---|
| Isoniazid (INH) | Pyridoxine (Vitamin B6) | 1 g IV per gram of INH ingested; essential for INH-induced seizures |
| Methotrexate | Leucovorin (folinic acid) | Bypasses DHFR blockade; given within 24 hrs |
| Lipophilic drugs (TCAs, CCBs, local anesthetics - bupivacaine) | Intravenous Lipid Emulsion (ILE) | Sequesters lipophilic drug away from cardiac tissue ("lipid sink") |
| Envenomations - Crotaline snakes (rattlesnakes, copperhead) | Crotalidae Fab antivenom | Better safety than older equine-derived antivenoms |
| Black widow spider | Latrodectus antivenom | For severe pain unresponsive to opioids; IV calcium is ineffective |
| Heparin / LMWH | Protamine | Only partially reverses LMWH |
| Dabigatran | Idarucizumab | Specific monoclonal antibody fragment |
| Factor Xa inhibitors (rivaroxaban, apixaban) | Andexanet alfa | Recombinant Xa decoy molecule |
Sources: Goldman-Cecil Medicine (Table 96-6), Rosen's Emergency Medicine (Chapters 151-152), Lippincott Illustrated Reviews: Pharmacology