Ever wondered how Paracetamol (or Acetaminophen for our American friends) works? Well, wonder no more. Here’s the explainer with the what, how, why, side effects and history and pharmacology to boot (two advanced sections in the 2nd half).
Paraacetylaminophenol. that’s far too complicated to say so we call it acetaminophen if you’re from the us or japan or paracetamol if you’re from pretty much everywhere else in the world. now, it’s a really common awesome amazing painkiller and you might also know it by its common brand names like tylenol, calpol, or
Panadol. why do you need it? well it’s a really awesome painkiller and it’s step one on our painkiller ladder. it’s also good at treating fever because it reduces your body temperature just a little bit as well. it’s so good in fact that it’s the most commonly used painkiller in the world and is on the who list of
Essential medicine. now i mentioned the pain ladder earlier that’s a concept from the world health organization from about 1986 where they said ‘these are the painkillers you start on and then if they don’t work you add these in, and then these, and then these’ and so on and so on. it’s a pretty good concept and we still
Kind of use it today. note that i said add in that’s the key to good pain relief so often painkillers are additive you always look to start simple and then you add others in over time. how does it work? well i mean… have a couple of guesses but in order to explain how a painkiller works i probably need to
Explain a little bit about pain. so what is pain? sensory or emotional experience associated with degree of your pain is not just the pressure it’s also things like personality and emotion can go into it as well, but it’s awesome – pain keeps us with nociceptors – that’s the fancy name for the receptors which are
Responding to things and you have a ton of them and loads of them work in loads of different ways – some respond to pressure and hard pressure soft pressure, some to heat, to cold, to spice and so on. when a receptor is activated it shoots off a signal to your spinal cord and when that happens well number one there’s a
Reflex which tends to move your hand or something else – away from the pain, and two it shoots off more signals to your brain and your brain perceives the pain and turns the signal into an experience. now paracetamol probably works centrally in the brain and the spinal cord activating pain inhibiting pathways and blocking
Receptors which trigger pain signals… but like i said we’re not entirely sure how it works. side effects – well it can cause pretty safe drug. that is when it’s taken in the right dose. overdosing on paracetamol is extremely dangerous – it leads to acute liver failure if you don’t catch that early and sometimes
Even if you do it can lead to extremely unpleasant symptoms and sometimes even death. it’s worth pointing out that some people have had acute liver failure just from a little overdose it’s not like they’ve been like chugging the bottle or anything, they’ve just taken a few doses too many. often the maximum dose of
An adult is about four grams a day so don’t go over that, oh and another word of warning – what we see pretty commonly in hospital is that some drugs contain paracetamol and you might not know it and that leads to accidental overdoses. a really common drug is co-codamol – that’s a stronger painkiller because it contains an
Opioid called codeine but the ‘co’ in co-codamol is paracetamol and some people don’t know that and they take their dose, so don’t make that mistake! but look, as always if you don’t feel right when you’re taking a drug just talk to your doctor. of you but please do subscribe before you go! okay for those of you
Who are sticking around here’s the history and the pharmacology – two sections which i’m putting in because most people, even a lot of doctors don’t know where these drugs came from or what they actually do to you. so the history – well the story of paracetamol isn’t one of systematic research and cautious evaluation
But rather one of serendipity, errors and failure. whippersnapper medics asked their famous professor of their patients who had a ton of ailments which included a worm infestation. now kussmaul suggested that they try naphthalene which was thought of as a gut disinfectant. it didn’t work, but much to their surprise
The patient’s fever subsided shortly after being given that drug. now that was unusual that never happened before but out that the pharmacy had mixed up the drugs and instead of giving them naphthalene it had given them acetanilide. now research began on acetanilide and it bloody worked! yeah you had this
Weird side effect where the skin turned a bit blue but don’t worry about that it was mass produced of course later on it was found that the bluish skin was actually the drug destroying your hemoglobin, so later on search for a safer chemical synthesized a compound called phenacetin. following this scientists tried
To find another drug with a better side effect profile and voila they didn’t use that because when testing it one of the scientists saw that it turned your blood blue like before so set it aside. this on hindsight years later people realize there’s probably an error because of that scientist but whatever
Paracetamol was put on the back burner until about 1946 when a few american scientists realized that paracetamol was actually the main metabolite of phenacetin and it was actually much safer and more active than the other one. i mean it did produce a biproduct called napqi – a very dangerous reactive chemical but
Don’t worry about that we’ll come back to that later. indeed phenacetin was becoming a bit too dangerous anyway as watchmakers in switzerland who took a lot of it to deal with the headaches from staring at those tiny mechanics all day long ended up dying of kidney failure. so paracetamol took off but it was only decades
Later when people realized that paracetamol causes liver failure in overdose because of that napqi bastard, and i know i said paracetamol was pretty safe earlier but as time goes on we’re actually beginning to learn of the more negative side effects of paracetamol especially when you take it long term. so it is
Paracetamol for too much longer in fact probably wouldn’t approve it for human use! like i said we don’t know for sure. less than inhibits prostaglandin produced by cox, not only in the central nervous system but also in the peripheral tissues. now what does that mean? so when your tissues get damaged they
Break and release a ton of inflammatory mediators and those mediators lead to pain – some of those mediators are fully formed and they’re good to go, some are like precursor chemicals which need to react with an enzyme to turn them into a mediator which then signals the pain. prostaglandins are little lipid
Hormones which are one of those potent mediators. once your prostaglandin is going you’re going to feel pain but they have to be made and those paracetamol interferes with the cox enzymes which reduces your pain. it doesn’t interfere in it that’s why they’re known as a weak painkiller but they’re a painkiller
Nonetheless. paracetamol also seems to break down in the central nervous system forming something called am404 which seems to interfere with your cannabinoid receptors and that’s what cannabis hits, which explains some of the pain relief as well. and while here it also reduces the production of il-1 which is a cytokine
Which leads to increased temperature in fever so helping to reduce fever as well by cutting off il-1. the key issue we spoke about is that about napqi and that’s highly reactive and dangerous. your liver can deal with a little bit because it’s got a substance called glutathione in it but in overdose you use up all
The glutathione which means the napqi starts burning away the liver. in the uk it causes about 200 deaths per year so don’t overdose kids. and there you go – paracetamol a really interesting painkiller discovered by luck that we still don’t really sell it to you over the counter. lots more drug explainers in
This series so see you next time please do like and subscribe. toodles!
Transcribed from video
What is Paracetamol and how does it WORK? – Acetaminophen, Calpol, Tylenol By Stealth Health
