Paracetamol Overdose

Paracetamol Overdose

What is Paracetamol?

Paracetamol is a very common drug for treating fever and mild to moderate pain. In all the countries these are available as over-the-counter drug. That means you don’t need a doctor’s prescription for purchasing paracetamol.

How Does It Work?

• For fever: They block the chemical messengers in the brain which regulate body temperature.
• For pain relief: They block the chemical messengers in the brain which give the feeling of pain.
  It takes up to an hour to start working and works for around 5 hours.

Dosage of Paracetamol

Paracetamols are available as tablets, capsules, syrup, powder and suppositories in different strengths:

• Tablet: 500mg or 1 g
• Capsule: 500 mg
• Syrup: 120 mg, 250 mg and 500 mg in 5ml.
• Powder: You have to add the prescribed amount in water.
• Suppository: It is placed in a patient’s bottom. Strength is 60mg to 1g.

For adults (>12 years of age) the dosing is 500 to 1000mg every four to six hours.
For children (1 month to 12 years)the dosing is 15 mg per kg of body weight, which can be given every four to six hours.

What Happens After Overdose of Paracetamol?

After administration of paracetamol, 20% of it is processed in the intestine and rest in the liver. It’s metabolism in liver produces a toxic byproduct N-acetyl-p-benzoquinone imine or NAPQI.
When right dose of paracetamol is administered, a small amount of NAPQI is produced and it is quickly inactivated by conjugation with glutathione.
In case of paracetamol overdose, liver produces more NAPQI and enough glutathione is not available to nullify its toxicity. As a result, liver gets damaged severely and it may lead to renal failure and death also.
For first 24 hours, a patient remain asymptomatic or can have non-specific symptoms like nausea, vomiting etc.
Paracetamol is the most common drug responsible for intentional and unintentional poisoning and toxicity.
Intentional overdose: Since it an OTC drug, people can collect huge number of paracetamol pills from pharmacy. For committing suicide, people swallow them altogether.
Unintentional overdose: People intake extra paracetamol to get relief from intense pain or high fever.
In case of children, caregiver may give overdose by mistake.

When Overdose Starts?

For adults ingestion of 150mg per kg of body weight or higher can lead to serious adverse effects. The effect of overdose vary for different persons depending on their age and co-morbidities.
When a person intakes total around 12g of paracetamol, the result is fatal.

How to Treat Paracetamol Overdose?

There are many ways to treat this:

• Decreasing absorption: The interventions like gastric lavage, activated charcoal, and ipecacuanha (ipecac syrup, an emetic) reduce paracetamol absorption in the gastrointestinal tract.
• Preventing the production of NAPQI: Cimetidine is an antidote that is able to stop production of further NAPQI in the liver.Detoxifying NAPQI: Methionine, cysteine, cysteamine, dimercaprol, or acetylcysteine are antidotes those can detoxify NAPQI.
• Procedures to remove paracetamol from bloodstream: Intermittent haemodialysis, intermittent haemoperfusion, continuous renal replacement modalities, or charcoal haemoperfusion are the techniques used for this purpose.

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References:

1. Jóźwiak-Bebenista M, Nowak JZ. Paracetamol: mechanism of action, applications and safety concern. Acta Pol Pharm. 2014 Jan-Feb;71(1):11-23. PMID: 24779190.
2. https://www.nhs.uk/medicines/paracetamol-for-adults/how-and-when-to-take-paracetamol-for-adults/
3. https://www.tga.gov.au/news/news/recommended-paracetamol-doses
4. Chiew AL, Gluud C, Brok J, Buckley NA. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev. 2018 Feb 23;2(2):CD003328.