Скачать или смотреть Paracetamol (Acetaminophen) Overdose And Toxicity Explained | How It And Alcohol Destroy Your Liver

Paracetamol or acetaminophen poisoning is one of the most common causes of fatal and non-fatal liver damage.

And it’s also one of the most common questions that people would call a pharmacy late at night to ask about.

Paracetamol is widely available in supermarkets and pharmacies worldwide and is commonly used to treat mild pains from things such as headaches and body aches, and also to reduce fever.

It’s also got some other uses such as an opioid sparing agent.

Overdosing appears to be very frequent due to people not interpreting the instructions on how to use paracetamol correctly, failing to recognise that it’s found in many different products, or feeling that their pain isn’t controlled after 1 or 2 tablets in an hour so they take more.

Conversely, it’s a popular pill that people like to try and “end themselves”.


When paracetamol enters the body, the liver breaks it down into many different metabolites or smaller molecules that go on and have exerted effects in the body.

Majority of these metabolites are non-toxic, broken down as a result of phase 2 metabolism with conjugation reactions involving sulfate and glucuronide.

However, a small portion of paracetamol is metabolised by our biggest liver enzyme system known as the cytochrome p450 system.

Specifically it requires 2 enzymes known as CYP2E1 and CYP3A4.


When these 2 enzymes, 2E1 and 3A4 metabolise paracetamol, they produce a highly reactive metabolite known as N-acetyl-p-benzoquinone imine, or NAPQI for short.

Under normal conditions, such as taking the recommended dose, and not being intoxicated by certain drugs such as alcohol, the body rapidly detoxifies this so that it causes no damage to our liver.

In the case that we overdose on paracetamol by taking too many pills i.e. dosing every hour instead of 4 to 6 hours, or taking 6 pills at once.

The normal systems involving sulfate and glucuronide are overwhelmed and so the body employs more of the p450 system using 2E1 and 3A4 to get rid of it.

As a result of more 2E1 and 3A4 being deployed, more of this NAPQI substance is being produced. And with that, the system that would normally detoxify this and get rid of it before any damage occurs, also gets overwhelmed through a rate limiting reaction.


Therefore more NAPQI is just sitting in your liver, highly reactive and eyeing off all the cells surrounding it, and begins attacking your liver cells, resulting in acute liver necrosis or damage.


That’s the mechanism in a nutshell, it does have a few variables such as the actual dose of paracetamol taken, the levels of glutathione in the liver (this is the molecule that makes NAPQI unreactive), as well as person’s history with other substances namely alcohol.

Now you’re probably wondering what’s alcohol got to do with paracetamol poisoning so let me break it down.


Ethanol as we know as alcohol is broken down in the body to a highly toxic compound known as acetaldehyde which is what causes damage to your body when you have drunk too much.
It also contributes to all the sensations you feel if you get drunk due to it being toxic to your brain, as well as contributing to hangovers.

So naturally, your body wants to get rid of your unhealthy habit quickly, and it uses that little enzyme we spoke about before, CYP2E1.

Now it wants to get rid of the toxin very quickly so if you are within the “standard drinks per hour” guideline then its likely your body will be neutralising the toxin as it is forming.

But if you go beyond that and drink more, this enzyme has to work harder. So you’re body does the ingenious thing and produces more 2E1, a lot more.

But now, if you take paracetamol with that extra pile of 2E1 sitting in your liver ready to go, you metabolise the paracetamol much quicker and using more of the p450 system than you otherwise would need, resulting in more NAPQI being produced quicker, and potentially overwhelming your body again.



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