Things you should know about painkillers: Paracetamol and its toxicity

Paracetamol overdose can occur intentionally or accidentally - the latter due to the high number of combination products available over-the-counter.

Paracetamol (more commonly known as acetaminophen) is so popular that GPs wrote 22.5m prescriptions for it in 2013. Around 200m packets of it are sold annually, accounting for two-thirds of the UK market for over-the-counter painkillers. It is widely viewed as cheap, safe and effective. Packets can be bought for as little as 19p and are used by millions of people daily over the world to combat a host of common complaints. It is a key component in many medications that we all know for use against the common cold or flu, or for minor pains such as menstruation, arthritis, back pain and high temperatures. Paracetamol became very popular in1960s in the wake of fears that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen could cause gastric bleeding, ulcers and other serious side-effects.

As stated it’s use is ubiquitous, particularly during winter for colds and flu, and it is safe to use in the appropriate amounts that are recommended but alarmingly it is very easy to ‘top up’ your dose without being aware of the consequences. Paracetamol overdose can occur intentionally or accidentally – the latter due to the high number of combination products available over-the-counter. This is very easy to do when you are taking a variety of remedies both day and night for a heavy cold. There are also frequent cases of accidental overdose in children due to inappropriate dosage due to their lower body weight (toxicity can occur at 250mg/kg bodyweight)

The normal dose for adults is 1 to 2 normal strength tablets (500mg to 1,000mg) every 4 to 6 hours. You should not take more than 8 normal strength tablets in 24 hours (4,000mg).

If levels exceed the above paracetamol can cause liver damage (hepatotoxicity) if you take larger doses than recommended. Adults must not take more than 4000 mg in a 24-hour period.

Potentially paracetamol can cause serious side effects, such as extreme fatigue, fever, difficulty urinating, yellowish skin or eyes (jaundice), discoloured urine or stool, bloody stool or bloody vomit, lightheadedness, bruising, and symptoms of an allergic reaction, such as rashes, swelling and difficulty breathing. Taking too much paracetamol together with alcohol might actually damage your liver.

After taken orally, paracetamol is well absorbed and it reaches  peak plasma concentration in about one hour after consumption but this may be 30 minutes if taken in liquid form. Paracetamol is eventually mainly inactivated by the liver by two metabolites; glucuronide or sulfate after which it is excreted through your urine.

• When taken in overdose this pathway can become flooded, causing paracetamol to be metabolised by a backup different pathway.

• Glutathione, acting as a secondary emergency pathway, quickly stops any harm by inactivating excess paracetamol.

• But when glutathione is itself depleted to less than approximately 30% this leads to cell death in the liver and in the kidney.

In order to reduce the incidence of paracetamol overdose, legislation was passed in the UK in 1998 to limit the number of tablets that could be bought in one purchase: 16 tablets at present (up to 32 tablets in pharmacies). Limiting pack size has reduced sizes of overdoses and numbers of deaths and liver transplantations in England and Wales.