Toxicology & Poison Antidotes
1. What this chapter covers, and how NEET PG actually tests it
Toxicology stems give a cluster of signs and ask for the poison, the antidote or the immediate management step.
The organising principle is that the toxidrome names the mechanism, and the mechanism names the antidote.
A toxidrome is the constellation of vital signs, pupils, skin and mental state produced by a class of agents acting on one receptor system.
| Toxidrome | Pupils | Skin | Other |
|---|---|---|---|
| Cholinergic | Constricted | Sweating, wet | Salivation, bronchorrhoea, bradycardia, fasciculation |
| Anticholinergic | Dilated | Dry, flushed | Fever, retention, delirium, tachycardia |
| Opioid | Pinpoint | Normal | Respiratory depression, coma |
| Sympathomimetic | Dilated | Sweating | Hypertension, tachycardia, agitation |
| Sedative-hypnotic | Normal or small | Normal | Depressed consciousness, preserved vitals |
Wet and dry separates the two that look most alike. Cholinergic patients are drenched and their pupils are small; anticholinergic patients are dry, flushed and febrile with large pupils.
2. General management
2.1 The order of priorities
Resuscitation always precedes identification of the poison, because most deaths are from airway loss, hypoxia, arrhythmia or seizure rather than from the specific toxin.
The universal antidote does not exist, and the older combination sold under that name is obsolete and harmful.
Only a small number of poisons have a specific antidote, so supportive care remains the mainstay in most poisonings.
Every case of poisoning is a medicolegal case, so the police must be informed and the entry made in the register, but treatment is never delayed for either step.
The clothing, vomitus, any container brought with the patient and the first sample of gastric aspirate should all be preserved, because they are frequently the only material that identifies the agent.
2.2 Decontamination
Gastric lavage is now used sparingly, chiefly within about one hour of a life-threatening ingestion in a patient with a protected airway.
Lavage is contraindicated after corrosive ingestion and after hydrocarbon ingestion, because a corrosive will injure the oesophagus a second time on the way up and a hydrocarbon carries a high risk of aspiration pneumonitis.
Activated charcoal adsorbs most organic poisons and is most effective within the first hour.
It does not adsorb metals, alcohols, corrosives, or the common ions, which is worth remembering as a short list.
| Not adsorbed by charcoal |
|---|
| Iron, lithium and other metals |
| Alcohols including methanol and ethylene glycol |
| Corrosive acids and alkalis |
| Cyanide, boric acid and simple ions |
2.3 Enhancing elimination
Urinary alkalinisation with sodium bicarbonate traps weak acids in the urine and is used for salicylate and phenobarbitone.
Haemodialysis is effective for small, water-soluble molecules with low protein binding and small volume of distribution, which is why methanol, ethylene glycol, lithium, salicylate and metformin are dialysable and tricyclics are not.
Multiple-dose activated charcoal interrupts enterohepatic recirculation and is used for carbamazepine, dapsone, phenobarbitone, quinine and theophylline.
2.4 Samples for analysis
The chemical examiner can only find what the doctor sends, in a state fit for testing, so sampling is examined as a topic in its own right.
At autopsy the routine viscera are the stomach with its contents, a portion of small intestine with contents, a piece of liver, one kidney, and blood and urine where available.
Saturated saline is the preservative for viscera and rectified spirit for blood, and formalin must never be used, because it fixes tissue and destroys or masks most poisons.
Rectified spirit is also unsuitable where alcohol, paraldehyde or acetic acid is suspected, since the preservative would confound the very analysis being requested.
Blood for alcohol estimation is preserved with sodium fluoride, which inhibits glycolysis and prevents both loss of alcohol and its generation by fermentation, together with potassium oxalate as an anticoagulant.
Hair and nails are collected where chronic heavy metal poisoning is suspected, because arsenic and other metals bind keratin and persist there for months.
Each container is separately sealed, labelled and accompanied by a sample of the preservative itself, so that any contamination in the preservative can be excluded.
2.5 Alcohol
Ethanol is the most commonly encountered intoxicant in casualty and in road traffic work.
It is absorbed rapidly, distributed in total body water, and eliminated by zero-order kinetics at roughly 15 to 20 milligrams per hundred millilitres per hour once the enzyme is saturated.
The legal limit for driving in India is 30 milligrams per hundred millilitres, well below the level at which most people feel impaired.
Clinical assessment of drunkenness records gait, speech, pupils, nystagmus, the smell of the breath and the ability to perform simple coordinated tasks, and must always consider head injury, hypoglycaemia and other poisonings as alternative explanations.
The Widmark formula relates the quantity consumed to the expected blood concentration through body weight and a distribution factor, and it is used to work backwards to the level at the time of an incident.
3. Poisons that dominate Indian practice
3.1 Organophosphates
Organophosphate insecticide is the commonest serious poisoning in rural India.
It inhibits acetylcholinesterase irreversibly, so acetylcholine accumulates at every cholinergic synapse and the clinical picture is simply excess acetylcholine everywhere.
Muscarinic effects give the classical picture of salivation, lacrimation, urination, defaecation, gastrointestinal cramps, emesis, bronchorrhoea, bradycardia and miosis.
Bronchorrhoea and bronchospasm kill, not the bradycardia, which is why atropine is titrated to drying of secretions rather than to heart rate.
Nicotinic effects give fasciculation, weakness and eventually paralysis, and these do not respond to atropine at all.
Pralidoxime reactivates the enzyme by removing the phosphate group, but only before ageing, the irreversible loss of an alkyl group that locks the enzyme permanently.
Ageing occurs within hours for some compounds, which is why pralidoxime must be given early to be of any use.
Two later syndromes are examined. The intermediate syndrome appears one to four days later with proximal and neck flexor weakness and respiratory failure, and organophosphate-induced delayed neuropathy appears two to three weeks later as a distal sensorimotor neuropathy.
Carbamates inhibit the same enzyme but reversibly and without ageing, so the illness is shorter and pralidoxime is generally unnecessary.
3.2 Aluminium phosphide
The rice tablet used as a grain fumigant is among the most lethal poisons in India, with mortality that has remained high for decades.
On contact with moisture and gastric acid it releases phosphine gas, which inhibits cytochrome c oxidase and blocks cellular respiration.
The classic clues are a garlic odour on the breath, vomiting, profound refractory shock and severe metabolic acidosis.
There is no antidote, and management is supportive, with early ventilation, aggressive haemodynamic support and correction of acidosis.
Gastric lavage with potassium permanganate is used to oxidise residual phosphide, and coconut oil is described as a means of reducing further phosphine release.
3.3 Corrosives and hydrocarbons
Acid ingestion causes coagulative necrosis with a limiting eschar, while alkali causes liquefactive necrosis that penetrates more deeply.
Alkali therefore carries the greater risk of perforation and of late oesophageal stricture.
Neither lavage nor neutralisation nor emesis is appropriate, and endoscopy within the first day guides management.
Kerosene ingestion in children is dangerous through aspiration rather than absorption, so the risk is chemical pneumonitis and lavage is avoided.
4. Metals and their chelators
| Metal | Characteristic features | Chelator |
|---|---|---|
| Arsenic | Rice-water diarrhoea, garlic breath, Mees lines, peripheral neuropathy | Dimercaprol, succimer |
| Lead | Abdominal colic, wrist drop, basophilic stippling, gum line, encephalopathy in children | Calcium disodium edetate, dimercaprol, succimer |
| Mercury | Tremor, gingivitis, erethism, acrodynia in children | Dimercaprol, succimer, penicillamine |
| Copper | Haemolysis, hepatic and renal failure | Penicillamine |
| Iron | Vomiting and haematemesis, then a latent phase, then shock and hepatic failure | Desferrioxamine |
Arsenic is the classic homicidal poison, because it is tasteless, mimics gastroenteritis and can be given in repeated small doses.
It is detected long afterwards in hair and nails, because arsenic binds keratin, which is why those are the samples requested in exhumation cases.
Lead is the classic occupational and environmental poison, and children are affected more severely because the developing brain is more susceptible and absorption is greater.
The iron latent phase is a well-known trap: a child appears to improve some hours after ingestion and then deteriorates into shock and hepatic failure.
5. Drug overdoses that carry specific antidotes
| Poison | Antidote | Note |
|---|---|---|
| Paracetamol | N-acetylcysteine | Replenishes glutathione |
| Opioids | Naloxone | Short-acting, may need infusion |
| Benzodiazepines | Flumazenil | Rarely used, may precipitate seizures |
| Methanol, ethylene glycol | Fomepizole or ethanol | Competes for alcohol dehydrogenase |
| Digoxin | Digoxin-specific antibody fragments | For arrhythmia or hyperkalaemia |
| Warfarin | Vitamin K, prothrombin complex | Reversal depends on urgency |
| Heparin | Protamine sulphate | Forms an inactive complex |
| Cyanide | Hydroxocobalamin, sodium thiosulphate, nitrites | Binds or supplies sulphur |
| Beta blockers | Glucagon | Bypasses the beta receptor |
| Isoniazid | Pyridoxine | Restores GABA synthesis |
| Methotrexate | Folinic acid | Bypasses dihydrofolate reductase |
| Organophosphates | Atropine and pralidoxime | Atropine for muscarinic, oxime for nicotinic |
Paracetamol is hepatotoxic because a saturated conjugation pathway diverts metabolism to the reactive intermediate, which glutathione normally detoxifies until stores are exhausted.
N-acetylcysteine works by replenishing glutathione, and it is close to fully protective if given within eight hours.
Methanol and ethylene glycol are harmless until metabolised, so the antidotes work by blocking alcohol dehydrogenase and preventing the formation of formic acid and oxalate respectively.
Methanol blinds through formic acid injuring the optic nerve, and ethylene glycol produces renal failure with calcium oxalate crystals in the urine.
Tricyclic antidepressant overdose has no true antidote, and sodium bicarbonate is given for the widened QRS because sodium loading overcomes the sodium channel blockade.
Isoniazid causes seizures by depleting pyridoxine and therefore GABA, and the pyridoxine dose is matched gram for gram to the isoniazid ingested.
6. Envenomation
6.1 Snake bite
Four species account for most Indian mortality: the cobra, the common krait, Russell's viper and the saw-scaled viper.
Elapid venom is neurotoxic, producing ptosis, ophthalmoplegia, bulbar weakness and respiratory paralysis without much local reaction.
Viper venom is vasculotoxic, producing severe local swelling and necrosis, coagulopathy, bleeding and acute kidney injury.
The twenty-minute whole blood clotting test is the practical bedside investigation, since failure of a few millilitres of blood to clot in a plain glass tube within twenty minutes indicates a coagulopathic viper bite.
Indian antivenom is polyvalent against those four species, and it is indicated only for systemic envenomation or significant local progression, not for every bite.
Neostigmine with atropine benefits cobra bites specifically, because cobra venom acts postsynaptically and is therefore reversible by increasing acetylcholine.
Krait venom acts presynaptically, so anticholinesterase treatment does not help, and krait bites are notorious for painless nocturnal bites presenting with abdominal pain and paralysis on waking.
Tourniquets, incision and suction are all harmful and have been abandoned; the limb is immobilised and the patient moved quickly.
Antivenom reactions are common and are managed with adrenaline rather than by abandoning the antivenom, since untreated systemic envenomation is the greater danger.
Repeat dosing is guided by clinical response and by repeating the clotting test after six hours, because venom continues to be absorbed from the bite site.
6.2 Scorpion sting
The Indian red scorpion causes an autonomic storm with sweating, vomiting, hypertension followed by hypotension, and pulmonary oedema.
Prazosin is the specific treatment, because it blocks the alpha-adrenergic effects of the massive catecholamine surge that causes the myocardial dysfunction.
Scorpion antivenom exists and is used in severe cases, but prazosin remains the intervention with the clearest mortality benefit in Indian series.
7. Cellular poisons and the gases
Cyanide binds ferric iron in cytochrome c oxidase, so oxygen is delivered but cannot be used.
The consequences follow directly: venous blood stays bright red, arteriovenous oxygen difference collapses, and severe lactic acidosis develops within minutes despite normal saturation readings.
Sources include bitter almonds and apricot kernels, industrial electroplating, and combustion of polyurethane in domestic fires.
Hydroxocobalamin is the preferred antidote because it binds cyanide directly to form cyanocobalamin and is safe in a smoke-inhalation victim who may also have carbon monoxide poisoning.
Sodium thiosulphate supplies sulphur to rhodanese, which converts cyanide to thiocyanate for renal excretion, and nitrites work by generating methaemoglobin, which competes for the cyanide.
Nitrites are avoided in fire victims precisely because inducing methaemoglobinaemia in someone already carrying carboxyhaemoglobin removes still more oxygen-carrying capacity.
Carbon monoxide, phosphine and hydrogen sulphide belong to the same family of problems in that oxygen delivery or utilisation fails while the airway is intact, which is why pulse oximetry is unreliable across the whole group.
8. Plant poisons
| Plant | Toxin and features |
|---|---|
| Abrus precatorius | Abrin; used as a cattle poison in needle form, agglutinates red cells |
| Datura | Atropine and scopolamine; pure anticholinergic syndrome, used in highway robbery |
| Cerbera odollam and Thevetia | Cardiac glycosides; bradycardia, heart block, hyperkalaemia |
| Strychnos nux-vomica | Strychnine; glycine antagonism, opisthotonus with retained consciousness |
| Cannabis | Bhang and ganja; run amok described after heavy ingestion |
| Ricinus communis | Ricin; ribosomal inhibition, severe gastroenteritis |
Datura is the pure anticholinergic picture, and the phrase used to teach it is dry as a bone, red as a beet, blind as a bat, hot as a hare and mad as a hatter.
Strychnine is distinctive because consciousness is retained throughout the convulsions, since the toxin acts at spinal glycine receptors rather than in the brain.
9. Worked examples
Example 1. A farmer is brought unconscious with pinpoint pupils, drenched in sweat, with copious secretions and fasciculating muscles. What is the poison and the priority?
Small pupils with a wet patient is the cholinergic toxidrome, and fasciculation confirms nicotinic involvement, so this is organophosphate poisoning. Atropine is titrated to drying of secretions, with pralidoxime given early before the enzyme ages.
Example 2. A young man presents twelve hours after ingesting a grain fumigant tablet, with garlicky breath, vomiting and profound shock unresponsive to fluids. What is the antidote?
There is none. Aluminium phosphide releases phosphine, which blocks cellular respiration, and management is entirely supportive with early ventilation and haemodynamic support.
Example 3. A patient who drank illicit liquor has severe acidosis and visual blurring. What is the mechanism and treatment?
Methanol is converted by alcohol dehydrogenase to formic acid, which injures the optic nerve and drives the acidosis. Treatment blocks that enzyme with fomepizole or ethanol, with bicarbonate for acidosis and haemodialysis for severe cases.
Summary
Recognise the toxidrome first; it names the receptor system, which names the mechanism, which names the antidote.
Wet with small pupils is cholinergic; dry, flushed and febrile with large pupils is anticholinergic.
Resuscitation precedes identification, and most poisonings have no specific antidote at all.
Lavage is reserved for early life-threatening ingestion and is contraindicated after corrosives and hydrocarbons.
Charcoal does not adsorb metals, alcohols, corrosives or simple ions.
Dialysis works for small, water-soluble, poorly protein-bound poisons with a small volume of distribution.
Organophosphates cause excess acetylcholine everywhere; atropine is titrated to secretions, and pralidoxime must precede enzyme ageing.
The intermediate syndrome appears at one to four days and delayed neuropathy at two to three weeks.
Aluminium phosphide releases phosphine, blocks cellular respiration, smells of garlic and has no antidote.
Alkali causes deeper liquefactive injury than acid, and kerosene harms by aspiration rather than absorption.
Arsenic is the classic homicidal poison and is recovered from hair and nails long afterwards.
Iron poisoning has a deceptive latent phase before shock and hepatic failure.
N-acetylcysteine works by replenishing glutathione and is near-fully protective within eight hours.
Methanol and ethylene glycol are toxic only after metabolism, so the antidotes block alcohol dehydrogenase.
Sodium bicarbonate is given for a widened QRS in tricyclic overdose, and pyridoxine is matched gram for gram in isoniazid poisoning.
Elapid venom is neurotoxic and viper venom vasculotoxic; the twenty-minute whole blood clotting test identifies the latter at the bedside.
Neostigmine helps cobra bites because the venom is postsynaptic, but not krait bites, which are presynaptic.
Prazosin is the treatment for Indian red scorpion sting, because the damage comes from a catecholamine surge.
Datura gives a pure anticholinergic syndrome, and strychnine causes convulsions with consciousness fully retained.
Preserve viscera in saturated saline and blood in rectified spirit, never in formalin, and use sodium fluoride when alcohol is to be estimated.
The legal blood alcohol limit for driving in India is 30 milligrams per hundred millilitres, and elimination proceeds at roughly 15 to 20 milligrams per hour.
Cyanide blocks cytochrome c oxidase, so venous blood stays bright red; hydroxocobalamin is preferred in fire victims because nitrites would worsen oxygen carriage.
