Acute PARACETAMOL Poisoning.

Acute paracetamol poisoning

Paracetamol belongs to NSAIDs (non steroidal anti-inflammatory drugs)
Paracetamol is one of the most commonly used ‘over-the-counter’ analgesic for headache,body aches, mild migraine, musculoskeletal pain, dysmenorrhoea,fever, osteoarthritis etc.
Due to its broad spectrum of action and least immedate side effects, chances of acute poisoning are more than those drugs which on intake cause seriously side effects.
Paracetamol poisoning can occur accidentally or as an attempt to end one's life.

Risk factors for toxicity include alcoholism, malnutrition, and the taking of certain other hepatotoxic medications.

Acute paracetamol poisoning occurs especially in small children who have low hepatic glucuronide conjugating ability. If a large dose (> 150 mg/kg or > 10 g in an adult) is taken, serious toxicity can occur. Fatality is common with > 250 mg/kg.

MANIFESTATIONS
Early manifestations are just nausea, vomiting, abdominal pain and liver tenderness with no impairment of consciousness.

After 12–18 hours centrilobular hepatic necrosis occurs which may be accompanied by renal tubular necrosis and hypoglycaemia that may progress to coma.

Jaundice starts after 2 days.

Further course depends on the dose taken.

Fulminating hepatic failure and death are likely if the plasma levels are above the line joining 200 µg/ml at 4 hours and 30 µg/ml at 15 hours. If the levels are lower —recovery with supportive treatment is the rule.

**Mechanism of toxicity

N-acetyl-p-benzoquinoneimine (NAPQI) is a highly reactive arylating minor metabolite of paracetamol which is detoxified by conjugation with glutathione. When a very large dose of paracetamol is taken, glucuronidation capacity is saturated, more of the minor metabolite is formed—hepatic glutathione is depleted and this metabolite binds covalently to proteins in liver cells (and renal tubules) causing necrosis. Toxicity thus shows a threshold effect manifesting only when glutathione is depleted to a critical point.

In chronic alcoholics even 5–6 g taken in one day can result in hepatotoxicity because due to alcoholism more NAPQI is produced.

Paracetamol is not recommended in premature infants (< 2 kg) for fear of hhepatotoxicity.

US-FDA (2009) has recommended to reduce the amount of this drug in any single dosage form (tab./cap.) to 650 mg (in place of 1000 mg earlier limit), and the total daily dose for an adult to 2600 mg (in place of 4000 mg earlier).

The Rumack-Matthew nomogram

Source
https://goo.gl/images/zizig7

Also known as Rumack-Matthews nomogram or the Acetaminophen nomogram is an acetaminophen toxicity nomogram plotting serum concentration of acetaminophen against the time since ingestion in an attempt to prognosticate possible liver toxicity as well as allowing a clinician to decide whether to proceed with N-Acetylcysteine (NAC) treatment or not.

**Treatment

If the patient is brought early, vomiting should be induced or gastric lavage done.
Activated charcoal is given orally or through the tube to prevent further absorption.
Other supportive measures, as needed, should be taken.

Specific: N-acetylcysteine 150 mg/kg should be infused
i.v. over 15 min, followed by the same dose i.v. over the next 20 hours. Alternatively, 75 mg/kg may be given orally every 4–6 hours for 2–3 days.
It replenishes the glutathione stores of liver and prevents binding of the toxic metabolite to other cellular constituents.

Ingestion-treatment interval is critical; earlier the better. It is practically ineffective if started 16 hours or more after paracetamol ingestion.

source: KD TRIPATI MEDICAL PHARMACOLOGY