Analgesic Poisoning
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Direct answer
Paracetamol heads nearly every Indian household's medicine shelf and heads the analgesic poisoning list with it: above roughly 150 milligrams per kilogram taken acutely (lower with alcoholism, malnutrition or enzyme-inducing drugs), the drug saturates glucuronidation and sulphonation, shunting metabolism to cytochrome P450 and generating N-acetyl-p-benzoquinone imine (NAPQI), which exhausts glutathione and necroses the liver in a centrilobular pattern over two to four days. Salicylate poisoning runs the other course — tinnitus, hyperventilation, early respiratory alkalosis, then a high anion gap metabolic acidosis, dehydration and hyperpyrexia — and threatens children dosed repeatedly for fever. The two antidote lines decide everything: N-acetylcysteine replenishes glutathione for paracetamol (guided by the Rumack-Matthew nomogram treatment line), and sodium bicarbonate alkalinises urine and tissue for salicylates, with haemodialysis reserved for the severe and deteriorating.
What you must remember
- Paracetamol toxicity threshold: acute ingestion around 150 milligrams per kilogram or 7.5-10 grams in adults; chronic or co-ingested alcohol lowers it substantially.
- Mechanism in one line: overload of conjugation routes drives cytochrome P450-mediated NAPQI formation, glutathione depletion, and centrilobular hepatic necrosis.
- Clinical course: 24 hours of nausea or silence, then rising aminotransferases peaking at 72-96 hours, coagulopathy and encephalopathy — the quiet first day is the trap.
- Antidote: N-acetylcysteine, most effective within 8-10 hours, still beneficial later; oral loading 140 milligrams per kilogram followed by 70 milligrams per kilogram every four hours (intravenous protocols are standard in Indian hospitals).
- Nomogram: the Rumack-Matthew treatment line beginning at 150 micrograms per millilitre at four hours separates patients needing the antidote — plot only single acute ingestions with known timing.
- Salicylate syndrome: tinnitus, deafness, hyperventilation, sweating, hyperpyrexia; mixed acid-base disorder with respiratory alkalosis followed by high anion gap metabolic acidosis.
- Salicylate treatment: activated charcoal early, sodium bicarbonate to alkalinise urine (targeting urinary pH around 7.5-8) trapping salicylate as its ion, and haemodialysis for severe intoxication, seizures or falling pH.
- Reye syndrome: aspirin in children with viral illness is linked to this hepatic encephalopathy — the reason paediatric aspirin use collapsed.
Working through an overdose timeline
A 22-year-old woman swallows thirty 500-milligram paracetamol tablets at midnight after an exam result and reaches hospital at eight in the morning with only vomiting. The timing is gold: a four-hour-post-ingestion level is already behind, so treatment starts on exposure history alone — fifteen grams in a 50-kilogram adult is double the toxic threshold. N-acetylcysteine begins immediately while a level is awaited, and the level, when plotted on the Rumack-Matthew nomogram, sits well above the treatment line. The first twenty-four hours she looks insultingly well; on day two the ALT climbs into the thousands, the prothrombin time stretches, and on day three early encephalopathy appears with hypoglycaemia — the centrilobular necrosis declared on standard kinetics. Because the antidote was given inside ten hours, recovery is the expected outcome; had she presented on day three, the same units would be discussing transplantation criteria. Salicylate cases write a different file: the child dosed hourly for two days arrives already hyperventilating and acidotic, and the treatment is alkalinisation with bicarbonate while monitoring urine pH, potassium (alkalinisation wastes it) and clinical sedation — dialysis stands ready if the level, the mental state or the acidosis deteriorates.
Where the viva probes
The classic probe is why the paracetamol patient looks well on day one while the salicylate patient looks ill from the first hours — the expected answer contrasts direct pharmacological stimulation by salicylate with delayed toxic metabolite injury by NAPQI. The second favourite is the nomogram's limits: it cannot be used for staggered ingestions, chronic toxicity or unknown times — in those, treat on history and follow transaminases. Examiners also expect the alcoholism question (induced P450 plus depleted glutathione lower the threshold dangerously) and the forensic angle: paracetamol is a common co-ingestant in impulsive self-poisoning in India, and the doctor's duty includes psychiatric referral once the liver is safe, since repeatability is the real risk.
Frequently asked questions
What is the toxic dose of paracetamol in acute overdose?
Approximately 150 milligrams per kilogram or 7.5-10 grams in adults, with a lower effective threshold in alcoholics, malnourished patients or those on enzyme inducers.
How does N-acetylcysteine work as an antidote?
It replenishes glutathione stores, detoxifying NAPQI before it binds hepatocytes; it is most effective within 8-10 hours but still helps later.
What acid-base disturbance characterises salicylate poisoning?
Early respiratory alkalosis from direct stimulation of the respiratory centre, followed by a high anion gap metabolic acidosis — the classic mixed picture.
When is haemodialysis indicated in salicylate poisoning?
Severe or symptomatic intoxication with high levels, refractory acidosis, seizures, encephalopathy or renal failure despite bicarbonate therapy.
What is the medicolegal significance of analgesic overdose?
Paracetamol dominates impulsive self-poisoning in India, so every case is an intentional-overdose assessment until proven otherwise, with documentation, psychiatric evaluation and poisoning reporting.