Paracetamol or acetaminophen poisoning is one of the most common causes of fatal and non-fatal liver damage.
What’s up guys tom here and today let’s talk about paracetamol poisoning paracetamol or acetaminophen depending on what country you live in 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 up a pharmacy late at night to ask about paracetamol is widely available in pharmacies
And supermarkets around the world and is commonly used to treat things such as mild pains from a headache or body aches as well as to help reduce fevers from colds and flus it’s also got some other uses such as an opioid sparing agent but that’s a bit too technical and for another video but only if you like and subscribe with the notification belt on overdosing
Appears to be very frequent in people who don’t seem to interpret the instructions clearly so they follow their own set of instructions or people who take one to two tablets and expect their pain to go away within an hour and when it doesn’t they take more or in people who fail to recognize that paracetamol is actually available in a large number of different
Products that you can buy over the counter conversely it’s also a popular pill for people who are trying to end themselves but if you watch the rest of this video you’ll find out why it’s actually a really terrible choice so how does it kill us when paracetamol enters the body the liver breaks it down into many different smaller molecules known as metabolites
Each that will go and exert some sort of effect on the body such as the ones i mentioned above majority of these metabolites are non-toxic and if you’re a science buff like me they are broken down as a result of phase two metabolism using conjugation reactions which involve sulfates and glucuronide however a small portion of paracetamol is metabolized by our
Liver’s biggest enzyme system which is known as the cytochrome p450 system specifically it requires two enzymes in this overarching system and they are known as sip2e1 and sip 3a4 which i’ll refer to as 2e1 and 3a4 for short when these two enzymes 2e1 and 3a4 metabolize paracetamol they produce a highly reactive metabolite known as n-acetyl p benzoquinone imine
Also known as napqi for short under normal conditions such as taking the recommended dosages and not being intoxified by other drugs such as alcohol the body will very rapidly metabolize this and remove it before any damage occurs in the case that we overdose on paracetamol either by taking our doses every hour or every two hours or taking six pills at once the
Normal systems involving this sulfate and glucuronide are actually overwhelmed so when this happens the body will employ more of these 2e1 and 3a4 enzymes to come and take up some of the slack and this is since our body really doesn’t like all the random that we put in it and it will see everything we ingest as either a toxin or food so if it’s a toxin it’ll
Try and get rid of it as quick as it can as a result of more 2e1 and 3a4 being used more of the napqi product is being produced and at a more rapid rate and at a rapid rate so that it starts to accumulate and because of this accumulation there’s actually a system which involves glutathione which actually helps to react and pretty much make the nap qr inert or
Unreactive this system then becomes overwhelmed due to another rate limiting step as well as depletion of the actual molecule glutathione therefore we have more of this snap qi in our system wandering around eyeing off all of the liver cells that are looking back at it so it does what any other small molecule with an inferiority complex would do and it starts to
Randomly attack all of your liver cells and cause a huge amount of acute liver damage so that’s the mechanism in a nutshell it does have a few other variables that can affect how someone responds to this such as how much paracetamol they’ve taken do they have any other drugs or things such as alcohol in their system or their history with alcohol for that matter
And how much glutathione they naturally have present as an antioxidant in their liver now you’re probably wondering what the hell is your alcohol got to do with paracetamol and causing liver poisoning and death well let me try and break it down simplistically for you ethanol when it enters the body is broken down into a highly toxic compound known as acetaldehyde
Which causes a lot of damage to your body and is contributed to that drunk sensation you’re feeling essentially because it’s quite toxic to the brain and it causes damage as well as contributing to the hangover feelings that people get the next day so naturally your body wants to get rid of this unhealthy habit that you keep putting into it and so it uses the
Little enzyme we spoke about before sip 2e1 now in terms of how fast you get rid of the toxin the standard rule that most guidelines follow is that if you have one standard drink per hour that should be enough for your liver to be able to break down and get rid and remove all of the acetaldehyde that’s formed but generally people tend to have a couple more drinks
In that first hour and then they have a couple more drinks after that and in certain circumstances people like to just drink a lot of alcohol so how does the body react to that well your liver does this ingenious but very simple thing and it just produces more of the 2e1 enzyme last one standing winds well no because as much as that contributes to people
Building up a tolerance to their alcohol it actually has a very detrimental effect when they take paracetamol because now if you were to take paracetamol you have a large pile of this 2e1 enzyme sitting in your liver ready to go so that more and more of this enzyme system that otherwise wasn’t used as much is now being employed because it’s there and ready to
Go resulting in more of the napqi toxic product being produced which can lead to overwhelming that rate limiting step involving glutathione which then results in the napq sitting in your body for longer and then results in liver damage hence why a lot of doctors and medical professionals will recommend that anyone who’s a known alcoholic should avoid paracetamol
Or take a reduced dose simply because we don’t actually know how their body will react based on the level of enzymes they have so after all this you’re probably thinking i never want to take paracetamol again and the good news is if it’s a small overdose or even to some extent a large deliberate overdose if it’s caught within a couple of hours usually with the
Treatments provided there’s minimal effect on the liver and minimal repercussions to the body if it progresses beyond that time say past one or two days the liver will start to rapidly shut down due to all of the damage it’s incurred and eventually that’ll continue to progress very painfully until the liver finally gives out and death occurs unless you’re lucky
Enough to find someone who can transplant part of their liver to you so that you can actually survive so on a final note if you are taking paracetamol or it is recommended to you just remember to take it as prescribed by your doctor or your pharmacist or your medical professional just remember to let them know that if they have a youtube channel you’ll like their
Video and subscribe until next time i hope you enjoy your week do remember to follow me on instagram as well all the details are down in the description i’ll see you in the next one
Transcribed from video
Paracetamol (Acetaminophen) Overdose And Toxicity Explained | How It And Alcohol Destroy Your Liver By Tom Ryan Health and Medicine Explained
