Drug Poisoning & Antidotes

Toxicology is a perennial NEET PG favourite, and the single most exam-dense slice of it is the poison-to-antidote match. This module gives you the high-yield antidote table, the mechanism behind each rescue drug, the clinical clues that betray the poison, and the management flows examiners reward.

Why antidotes matter (and the general approach)

An antidote is any agent that counteracts the toxic effect of a poison by neutralising it, displacing it from its target, blocking its formation of toxic metabolites, or competing at the receptor. Only a minority of poisonings actually have a specific antidote — the vast majority are managed by supportive care + decontamination + enhanced elimination. The exam, however, loves the small list that does have a specific antidote, so master it cold.

The universal stepwise approach to any poisoned patient:

Resuscitate (ABCDE) → Identify the toxidrome → Decontaminate (activated charcoal / gastric lavage where indicated) → Give specific antidote if available → Enhance elimination (urinary alkalinisation, haemodialysis) → Supportive care & monitoring.

High-yield: Activated charcoal is the decontamination method of choice for most ingested poisons, ideally within 1 hour. It does NOT bind: iron, lithium, lead, potassium, alcohols (methanol/ethanol/ethylene glycol), acids, alkalis, hydrocarbons, cyanide — remember the mnemonic "PHAILS" (Pesticides/Petroleum, Hydrocarbons, Acids/Alkalis/Alcohols, Iron, Lithium/Lead, Solvents).

The master antidote table

This is the table that wins you marks. Learn the poison, the antidote, and the mechanism together.

Poison	Specific antidote	Mechanism of antidote
Paracetamol (acetaminophen)	N-acetylcysteine (NAC)	Replenishes glutathione; substrate for conjugation of toxic NAPQI
Opioids (morphine, heroin, fentanyl)	Naloxone	Competitive μ-opioid receptor antagonist
Organophosphates / carbamates	Atropine + Pralidoxime (2-PAM)	Atropine blocks muscarinic; pralidoxime reactivates acetylcholinesterase
Benzodiazepines	Flumazenil	Competitive GABA-A benzodiazepine site antagonist
Iron	Desferrioxamine	Chelates ferric (Fe³⁺) iron
Digoxin / cardiac glycosides	Digoxin-specific antibody Fab fragments	Bind free digoxin, removed renally
Methaemoglobinaemia	Methylene blue	Cofactor for NADPH-methaemoglobin reductase; reduces Fe³⁺ → Fe²⁺
Methanol / ethylene glycol	Fomepizole (or ethanol)	Inhibits alcohol dehydrogenase → blocks toxic metabolite formation
Cyanide	Hydroxocobalamin / Sodium thiosulphate + Sodium nitrite (Amyl nitrite)	Induces methaemoglobin which scavenges cyanide; thiosulphate → thiocyanate
Heparin	Protamine sulphate	Forms inactive complex with heparin
Warfarin	Vitamin K (phytonadione) ± FFP/PCC	Restores clotting factor synthesis
Dabigatran	Idarucizumab	Monoclonal antibody fragment binds dabigatran
Apixaban / Rivaroxaban	Andexanet alfa	Decoy factor Xa molecule
Beta-blockers	Glucagon	Bypasses β-receptor; raises cAMP via own receptor
CCB overdose	Calcium + insulin-dextrose (HIET)	Restores Ca influx; improves myocardial glucose use
Lead	Calcium disodium EDTA, DMSA (succimer), BAL (dimercaprol)	Chelation
Arsenic / mercury / gold	BAL (dimercaprol), DMSA, DMPS	Chelation
Copper (Wilson's)	D-penicillamine, Trientine	Chelation
Methotrexate	Folinic acid (leucovorin)	Bypasses dihydrofolate reductase block
Isoniazid	Pyridoxine (B6)	Replenishes GABA synthesis cofactor
Carbon monoxide	100% O₂ / hyperbaric O₂	Displaces CO from haemoglobin
Anticholinergics	Physostigmine	Centrally-acting cholinesterase inhibitor
TCA overdose	Sodium bicarbonate	Narrows QRS; protein binding + Na channel effect
Snake bite (viper/cobra)	Polyvalent anti-snake venom (ASV)	Neutralising antibodies

High-yield: Examiners love the "reverse" question — which poison does this antidote treat? Be equally fluent in both directions, especially for pralidoxime (OP only, not carbamate routinely), flumazenil (benzodiazepine), fomepizole (toxic alcohols), and glucagon (beta-blocker).

Paracetamol poisoning & N-acetylcysteine

The classic, most-tested overdose.

Pathophysiology: Most paracetamol is conjugated (glucuronidation/sulfation). A small fraction is oxidised by CYP2E1 to the toxic electrophile NAPQI (N-acetyl-p-benzoquinone imine), normally detoxified by glutathione. In overdose, glutathione is depleted → NAPQI binds hepatocyte proteins → centrilobular (zone 3) hepatic necrosis.

Clinical phases:

1. 0–24 h: Nausea, vomiting, malaise (or asymptomatic).
2. 24–72 h: RUQ pain, rising transaminases.
3. 72–96 h: Peak hepatotoxicity — fulminant hepatic failure, encephalopathy, coagulopathy, AKI.
4. 4 days–2 weeks: Recovery or death.

Investigation: Serum paracetamol level at ≥4 h post-ingestion, plotted on the Rumack-Matthew nomogram to decide NAC therapy. Also monitor INR, LFTs, creatinine, ABG, glucose.

High-yield: NAC is most effective if given within 8–10 hours of ingestion but is still beneficial later. It works by replenishing glutathione and acting as a glutathione substitute. King's College Criteria predict need for liver transplant (pH <7.3, or the triad of INR >6.5 + creatinine >300 µmol/L + grade III/IV encephalopathy).

Opioid poisoning & naloxone

Toxidrome: The diagnostic triad of pinpoint (miotic) pupils + respiratory depression + CNS depression/coma. Bradycardia and hypotension may accompany.

Antidote — Naloxone: Pure competitive μ-opioid antagonist, very short half-life (~30–60 min), so repeat dosing or infusion is often required because most opioids outlast it. Reversal can precipitate acute withdrawal (lacrimation, mydriasis, piloerection, diarrhoea). Naltrexone is the long-acting oral analogue used for maintenance, not acute reversal.

High-yield: Pinpoint pupils that do NOT respond — think also of pontine haemorrhage and organophosphates. But pupillary constriction + respiratory depression reversed by naloxone = opioid.

Organophosphate poisoning

The Indian exam favourite (agricultural insecticide self-harm).

Mechanism: OPs irreversibly inhibit acetylcholinesterase → accumulation of acetylcholine → cholinergic crisis. Over hours, the enzyme-OP bond undergoes "ageing", after which pralidoxime cannot reactivate it — hence give 2-PAM early.

Toxidrome — remember the muscarinic mnemonic "DUMBBELS":

• Diarrhoea, Urination, Miosis, Bronchorrhoea/Bronchospasm, Bradycardia, Emesis, Lacrimation, Salivation.
• Nicotinic features: fasciculations, muscle weakness, paralysis (respiratory failure kills).

Management flow:

Decontaminate (remove clothes, wash skin) → Atropine (titrate to dry chest/secretions, doubling dose every 5 min) → Pralidoxime (reactivates enzyme before ageing) → Ventilatory support.

High-yield: Atropine treats muscarinic + central effects but NOT nicotinic (muscle weakness) — only pralidoxime reverses nicotinic signs. End-point of atropinisation is drying of bronchial secretions, not pupil size or heart rate.

Feature	Organophosphate	Carbamate
AChE binding	Irreversible (ages)	Reversible (spontaneous hydrolysis)
Pralidoxime	Indicated (give early)	Generally not needed/avoid
CNS penetration	Marked	Limited
Duration	Prolonged	Shorter

Intermediate syndrome: 24–96 h after OP poisoning — proximal muscle and cranial nerve weakness, respiratory failure; pralidoxime-unresponsive.

Iron poisoning & desferrioxamine

Common paediatric accidental ingestion.

Five phases: GI (haemorrhagic gastroenteritis, 0–6 h) → latent (6–24 h) → metabolic acidosis & shock → hepatic necrosis → late gastric/pyloric stricture.

Investigation: Serum iron at 4–6 h; abdominal X-ray may show radio-opaque tablets. Toxicity correlates with anion-gap metabolic acidosis and serum iron >500 µg/dL.

Antidote — Desferrioxamine: Chelates free ferric iron; the ferrioxamine complex gives urine a characteristic "vin rosé" (orange-pink) colour.

High-yield: Activated charcoal does NOT bind iron — whole-bowel irrigation with polyethylene glycol is the decontamination of choice for iron tablets.

Digoxin toxicity & digoxin-specific Fab

Features: Nausea/vomiting, confusion, xanthopsia (yellow-green vision), and almost any arrhythmia — classically bidirectional ventricular tachycardia and PAT with block. Toxicity worsened by hypokalaemia, hypomagnesaemia, hypercalcaemia, renal failure.

High-yield: Hyperkalaemia in acute digoxin toxicity is a marker of severity and an indication for Digibind (Fab). Do NOT give calcium for the hyperkalaemia (risk of "stone heart"). Digoxin-specific Fab is the definitive antidote.

Benzodiazepine poisoning & flumazenil

BZD overdose → CNS depression, but respiratory depression is mild unless co-ingested with opioids/alcohol; pupils usually normal.

Flumazenil reverses sedation but is used cautiously — it can precipitate seizures in chronic users or mixed TCA overdose and unmask arrhythmias. Hence supportive care is often preferred.

Methaemoglobinaemia & methylene blue

Met-Hb forms when haem iron is oxidised Fe²⁺ → Fe³⁺, which cannot carry oxygen. Causes: nitrites, dapsone, local anaesthetics (benzocaine, prilocaine), aniline dyes, sulphonamides.

Clues: Cyanosis unresponsive to oxygen, "chocolate-brown" blood, and a saturation gap (low SpO₂ but normal PaO₂).

Antidote — Methylene blue: Acts as a cofactor for NADPH-methaemoglobin reductase. Contraindicated in G6PD deficiency (ineffective + risk of haemolysis; use ascorbic acid/exchange transfusion).

High-yield: Pulse oximetry in methaemoglobinaemia tends to read ~85% regardless of true saturation because of the absorption characteristics of met-Hb.

Toxic alcohols & cyanide

Methanol → metabolised by alcohol dehydrogenase to formic acid → visual loss/blindness, putaminal necrosis, high anion-gap metabolic acidosis. Ethylene glycol → oxalic acid → calcium oxalate crystals, AKI, hypocalcaemia. Antidote: Fomepizole (preferred) or ethanol — both inhibit alcohol dehydrogenase, blocking toxic metabolite formation. Folate (methanol) and pyridoxine/thiamine (ethylene glycol) are adjuncts; haemodialysis removes the alcohol and corrects acidosis.

Cyanide inhibits cytochrome c oxidase (complex IV) → histotoxic hypoxia, lactic acidosis, bitter-almond breath, cherry-red skin, normal venous oxygen (arterialised venous blood). Antidote: Hydroxocobalamin (binds CN → cyanocobalamin) is first-line; alternatively the cyanide kit: amyl/sodium nitrite (induce methaemoglobin to bind CN) + sodium thiosulphate (provides sulphur for rhodanese → thiocyanate).

Key differentials — telling poisons apart by toxidrome

Toxidrome	Pupils	Key signs	Example agents
Cholinergic	Miosis	Wet (salivation, sweat, diarrhoea), bradycardia	Organophosphates
Anticholinergic	Mydriasis	Dry, hot, flushed, delirium, urinary retention	Atropine, antihistamines, TCAs
Opioid	Miosis	Respiratory depression, coma	Heroin, morphine
Sympathomimetic	Mydriasis	Tachycardia, hypertension, agitation, sweating	Cocaine, amphetamine
Sedative-hypnotic	Normal	CNS depression, normal vitals	Benzodiazepines, barbiturates

High-yield mnemonic (anticholinergic): "Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter" — and the heart runs alone (tachycardia).

Enhanced elimination essentials

• Urinary alkalinisation (sodium bicarbonate) → salicylates (aspirin) and phenobarbitone (weak acids; ion-trapped in alkaline urine).
• Haemodialysis → mnemonic "I-STUMBLE": Isopropanol, Salicylates, Theophylline, Uraemia, Methanol, Barbiturates, Lithium, Ethylene glycol.

Recently asked / exam angle

• Single best match questions: "Antidote for organophosphate?" → Atropine + pralidoxime; "Antidote for methotrexate?" → Folinic acid (leucovorin); "Antidote for INH overdose seizures?" → Pyridoxine.
• Mechanism-based: "NAC acts by ___" → glutathione replenishment. "Fomepizole inhibits ___" → alcohol dehydrogenase.
• Image/clinical vignette: chocolate-brown blood + cyanosis not improving with O₂ → methaemoglobinaemia → methylene blue (and the G6PD caveat).
• Contraindication traps: Flumazenil in chronic BZD/TCA co-ingestion (seizures); methylene blue in G6PD deficiency; calcium in digoxin toxicity.
• Charcoal exceptions ("which is NOT adsorbed by activated charcoal?") → iron/lithium/alcohols.
• Newer anticoagulant reversals: Idarucizumab (dabigatran), Andexanet alfa (apixaban/rivaroxaban) — increasingly tested.
• Digoxin toxicity ECG: bidirectional VT; hyperkalaemia indicating Fab therapy.

Rapid revision

1. NAC for paracetamol — best within 8 h; works by replenishing glutathione; nomogram = Rumack-Matthew.
2. Naloxone for opioids — short half-life, repeat/infuse; toxidrome = miosis + respiratory depression.
3. Organophosphate: atropine (muscarinic) + pralidoxime (nicotinic, give before ageing); end-point = dry secretions.
4. Iron: desferrioxamine → vin rosé urine; charcoal useless, use whole-bowel irrigation.
5. Digoxin: Fab fragments; hyperkalaemia = severity marker & indication; bidirectional VT.
6. Methaemoglobinaemia: methylene blue; chocolate-brown blood; contraindicated in G6PD.
7. Methanol/ethylene glycol: fomepizole/ethanol (block alcohol dehydrogenase) + dialysis; methanol → blindness, ethylene glycol → oxalate crystals + AKI.
8. Cyanide: hydroxocobalamin / nitrite + thiosulphate; inhibits cytochrome oxidase; bitter-almond breath.
9. INH seizures → pyridoxine; methotrexate → leucovorin; paracetamol → NAC.
10. Heparin → protamine; warfarin → vitamin K; dabigatran → idarucizumab; apixaban/rivaroxaban → andexanet alfa.
11. Beta-blocker → glucagon; CCB → calcium + high-dose insulin (HIET); TCA → sodium bicarbonate.
12. Dialysable poisons = I-STUMBLE; urinary alkalinisation for salicylates & phenobarbitone.