PharmacologyTier 1Medical Sciences concept

Specific antidotes in poisoning/overdose

Core concept

Antidotes work by one of four mechanisms - knowing which explains the timing and the endpoint

Mechanism	Examples
Receptor antagonism	Naloxone, flumazenil, atropine, glucagon
Enzyme reactivation or bypass	Pralidoxime, methylene blue, hydroxocobalamin
Substrate repletion / competition	NAC, folinic acid, ethanol/fomepizole, glucarpidase
Binding / chelation	Digoxin Fab, desferrioxamine, DMSA, activated charcoal, idarucizumab, andexanet, intralipid

Key detail

Poison	Antidote	Note
Paracetamol	N-acetylcysteine	Glutathione precursor; fully protective <8 h
Opioid	Naloxone	Titrate to respiratory rate; t-half shorter than most opioids
Benzodiazepine	Flumazenil	Rarely indicated - seizures, contraindicated with TCA co-ingestion
Digoxin	Digoxin-specific Fab fragments	Indications: K >5-5.5, life-threatening arrhythmia, haemodynamic instability, massive ingestion
Iron	Desferrioxamine	Chelation; treat on level and clinical stage
Methanol / ethylene glycol	Fomepizole (or ethanol) + dialysis	Blocks alcohol dehydrogenase; give folate/folinic acid (methanol), thiamine and pyridoxine (ethylene glycol)
Organophosphate	Atropine + pralidoxime	Atropine to dry secretions; pralidoxime before "ageing"
Beta-blocker	Glucagon, high-dose insulin-euglycaemia, calcium	Glucagon bypasses the beta-receptor to raise cAMP
Calcium channel blocker	Calcium, high-dose insulin-euglycaemia, vasopressors
Methaemoglobinaemia	Methylene blue 1-2 mg/kg	Contraindicated in G6PD deficiency -> use ascorbic acid or exchange transfusion
Cyanide	Hydroxocobalamin (or dicobalt edetate)	Turns urine and skin red
TCA / Na channel blocker	Sodium bicarbonate	Titrate to QRS narrowing
Warfarin	Vitamin K + prothrombinex (PCC)
Dabigatran	Idarucizumab
Factor Xa inhibitors	Andexanet alfa or PCC
Heparin	Protamine	Full reversal for UFH, ~60% for LMWH
Methotrexate	Folinic acid, glucarpidase	Folinic acid bypasses DHFR blockade
Isoniazid	Pyridoxine (gram for gram)	INH depletes pyridoxine -> refractory seizures
Local anaesthetic / lipophilic drug	Intralipid 20%	"Lipid sink"
Sulfonylurea	Octreotide (+ dextrose)
Lead / heavy metals	DMSA, dimercaprol, EDTA
Botulism, snake, spider	Antivenom / antitoxin	Australian snake antivenom by syndrome and region

Activated charcoal 50 g within 1-2 h for most ingestions with a protected airway
- Does not adsorb: metals (iron, lithium), alcohols, acids/alkalis, hydrocarbons
Multiple-dose charcoal for carbamazepine, dapsone, phenobarbital, quinine, theophylline
Enhanced elimination - urinary alkalinisation (salicylate, phenobarbital), haemodialysis (Lithium, Isopropanol, Methanol, Ethylene glycol, Salicylate - "I STUMBLED"/low Vd, low protein binding)

Clinical relevance

Antidotes are the minority of poisonings - supportive care, airway and time save most patients
Every deliberate ingestion: BSL, ECG (QRS, QTc), paracetamol level
Australian Poisons Information Centre 13 11 26 and the Toxicology Handbook risk assessment framework
Digoxin Fab dosing differs between chronic toxicity (2 vials empirically) and acute ingestion (dose from the amount ingested or the level) - the serum digoxin level becomes uninterpretable after Fab
Naloxone in a chronic opioid user: small titrated doses to avoid precipitating acute withdrawal and agitation
The mechanism predicts the endpoint - atropine to secretions, bicarbonate to QRS, naloxone to respiratory rate, NAC to ALT and INR

Correlations

Toxidrome recognition; TCA overdose
N-acetylcysteine mechanism in paracetamol toxicity
Dialysability of drugs in overdose
Anticoagulant reversal agents
Digoxin mechanism of action; methaemoglobinaemia

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