Paracetamol / Acetaminophen
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Welcome everybody to another episode of Dr. Matt and Dr. Mike's Medical Podcast. I'm your host, Dr. Mike Todorovich, and I'm joined by my co-host, Jean-Claude Van Damme, his fine, Dr. Matthew Barton. How are you, Matty? All right. Today, we are talking about paracetamol, also known as acetaminophen. Paracetamol or acetaminophen, I wish I could use it for the pain I'm experiencing right now from sitting across from you doing this podcast. And I'm going to be talking about paracetamol, which is a

So paracetamol, aka acetaminophen, has many different names. AKA N-acetylparaminophenol. Wow, I'm surprised that you're the one that said the chemical name and you did it well. So Matty, I just want to say that paracetamol is one of the most widely used analgesics and antipyretic medications globally. Globally. So if it was in the school of pharmacology, what class would it be in?

Well, you could say it's an analgesic. It's simple analgesic. So it's in the lower level class. Okay. With the simpletons. Analgesic 101 and antipyretic. So it's a firefighter. All right. So good for fevers. Yeah. Very good. To reduce fevers. But...

But let me say this because we're going to talk about this a little bit more. Not a very good anti-inflammatory. No, it wouldn't be classed as one. No. And that's an important distinction because there's other drugs, which we will allude to and we'll do episodes on them, that people probably confuse paracetamol with and take them interchangeably that are far better anti-inflammatory drugs.

And that's important distinction because often inflammation can cause pain and fever. And in some instances, it might be better to take the anti-inflammatory than this one. Right. But let's first go back a little bit. You classed it.

very simple analgesic. What else should people know about the class? So they're the class. Yeah, that's the class. What else should people know just as a basic when it comes to paracetamol? Are we going to call it paracetamol or acetaminophen? Paracetamol. Okay. I'm sorry, but that's just how it's used more broadly throughout the world. You don't have to apologize to me, mate. What else should people know? Actually, just with that,

Going back to the chemical name, N-acetylparaminophenol, the only difference between paracetamol and acetaminophen is they've just derived parts of the word from the same chemical name differently. But it's the same thing. Same thing.

Okay, anyway, so the clinical, so we've done the class, simple analgesic for mild to moderate pain and an antipyretic, antifever. Yeah. Now, when you look at clinical indications- Oh, wait, wait, wait. Brand names. What do people know this drug as? Oh, so in Australia, it would be Panadol, Panamax. Yeah. But I'm going to, that's actually a good point. I'll come to this in a second. In America, Tylenol. I think Tylenol was really how it was first marketed. And I think it was marketed as a kid's drug.

anti-fever medication. Really? I think initially it was for children. Now, the reason for that is because what was, when it came into use, probably around the 1950s, was, 1960s, what was its main competitor? Aspirin? Aspirin. Yeah. And so for why Tylenol came about was because you can't use aspirin really often.

children's fevers because of the risk of Reye's syndrome. Which we spoke about in the aspirin episode. And so just very quickly, what is that? Reye's syndrome is basically when you take aspirin, the way that it's metabolized in the liver, it starts to cause uncoupling within the liver mitochondria, which can lead to

liver cell injury, which then impacts the way that the liver cells process amino acids. So the de, what is it called? Deamination. Deamination. Okay. And so that means that the amino acids, because as we know, amino acids have a nasty end to them. Do they? Being the, I've got a mind blank.

Not the carboxyl on the other end. Amine end. Amine end, which becomes potentially ammonia. Right. And so if the liver can't do that anymore, ammonia products will start to build up, which then will go to the brain and cause like an ammonia-based encephalopathy, which is swelling of the brain. Brain stops working, coma, die. That's essentially...

With the Reye syndrome, this is liver into brain issue. More so when they are infected with a viral infection concurrent. Okay. So it's too big of a risk. Aspirin for kids. So the company that introduced Tylenol, they did it for this reason. Whilst the Panadol form, paracetamol, was...

Do you remember going back to your... Do you remember the ads going back when you were a kid? How did they market paracetamol? Do you remember? Was it for fever or for pain? No.

Do you remember they always used to say it's gentle on the stomach? Do you remember that? Yeah. So paracetamol was the alternative to aspirin for those that couldn't tolerate aspirin because of its GIT. And aspirin is an NSAID, a non-steroidal anti-inflammatory drug, which is an umbrella term for not just aspirin, but ibuprofen,

Salabrex, Duclofenac, and many of them, some of their most common side effects are gastric upset. And like you said, this is Panadol or Tylenol or acetaminophen has been marketed as an alternative that seems to be better for gastric

avoiding the gastrointestinal upset. And so just Tylenol is, you know how you said paracetamol and acetaminophen are basically just from the N-acetylparaminophenol. It's just taking different parts of it. Tylenol is the same. It's taken from the acetyl. It takes the TYL from acetyl. It takes the...

The EN from phen and then it takes the OL from phenol. Phenol, phen. So Tylenol is just like making acetaminophen and paracetamol. Yeah.

Just as a side point, which I came across in doing a bit of research, the Australian Pharmaceutical Regulatory Body, which we call the TGA, the Therapeutic Goods Association, which is equivalent to the FDA in America, they recently have reclassified, to some degree, paracetamol. In what regard? What is it? It's been shown... Well, paracetamol is a very safe drug in therapeutic...

Limits. Therapeutic dosage. But if it's exceeded, it can be very dangerous. Now, in Australia, but I'm assuming this is pretty much worldwide, one of the biggest causes of acute liver failure. Now, the reason for this, we'll get into the actual mechanism shortly, but basically, if you were to take this in high doses, it can be very liver toxic, which can result in your liver being knocked off, and then that can be

disastrous for the individual. Yes. Now, that can be done, not intended, but also it's the most common in terms of adolescents and young adults, the most commonly used medication for self-harm. Right. Probably because of its... Accessibility. That's right. Now, what the TGA has decided to do is make it more difficult to obtain medication

High amounts of it. Right. So by February 2025, which is two months time. That's soon. It's soon. Yeah. What they're going to do is restrict the amount of tablets per packet from 20 to 16. Yep. And that's probably going to go to speak to if you were to take a whole packet, it wouldn't be...

liver destroying. Well, I mean, the thought is that... It's still going to be excessive, but it potentially won't knock the whole liver off in one go. It's still not good for you. Don't do it. Do not do it. Whereas the other formulations, and this is... Remember we had that conversation with that head pharmacist at one of the conferences we spoke at? Yeah. She was...

the head pharmacist in one of the hospitals in Brisbane. And she spoke about how the health literacy of individuals in society, they don't really understand that paracetamol is in so many different formulations. So you, it could be like, there was like 12, no, there was 20 pages of different formulations of paracetamol in the textbook that I looked at, the online textbook. And so, so many of the formulations are with other things. So you could take,

paracetamol in all different release forms like quick release, easy absorbed, all those packaged different forms of Panadol.

That you've come across. And then there's the effervescent types where you chuck it into the water and it will bubble away and then it's just clear. Yeah. There's those. Then there's Lemsip, which is you take it with a tea. It's like a tea. Yeah. Cold and flu tablets. Then there's suspension-based ones. Then there's with codeine. So like Panamax. Not like Panamax with codeine. Panadine. Panadine Fort. Then there's even ones with caffeine now and that's for more headache-based pain. Then there is with...

and then you can have it in your cold and flu remedies. So with the more stimulants like Sudafedrine. So wait, you're saying that it sounds like Panadol, acetaminophen, paracetamol, Tylenol,

can be found in many different drug concoctions and that people probably don't necessarily realise that when they're taking a pain relief medication that they are taking acetaminophen. And now usually the formulation is such that each tablet's 500 milligrams and the dosage recommended per four hours is one gram, not exceeding, I think...

6 to 8 grams per 24-hour period. Now, if you had, let's just say, a really bad influenza case and you've got a splitting headache, you might go, I'm going to just take a couple of Panadols for the headache. Then you might go, well, I've still got these cold and flu symptoms, so I might go now have this cold and flu tablet. Exactly. And now it's got...

another gram of paracetamol in it and then you say oh i really feel like a warm cup of tea i'll have a limb sip there's another gram yeah and then you might have something else with codeine and not realize that you've now had four to five grams of paracetamol in one go has to deal with this that's right and it's and again not not good and like matt said earlier um

Acetaminophen is the leading cause of acute liver failure in the US and UK. One, because people don't realize how much they are taking over the period of time. Like Matt said, it is safe within its therapeutic recommended doses, but outside of this, it can be quite damaging. So-

So that kind of speaks to why the TGA, and also if you wanted to get the bigger boxes, you have to have that given to you by a pharmacist in a pharmacy. So you can't get those from the supermarkets anymore. Yeah. So these are just restricting the likelihood of having too much in one go. Now, so that's, we've spoken about the class, the clinical indications basically all...

analgesic based indications like headaches, back pain, toothache, muscle pain, sometimes arthritis. So, you know, they may have it in, what is it?

Osteopanadol, I think. Panadol-Osteo. Panadol-Osteo. I think that's just, again, one gram of paracetamol. And then cold and flu. But obviously fever. Very, very useful. I've used it extensively with my kids. For fever. For fever. Wonderful. Very, very beneficial. Made a huge difference when they have anything from flu-like symptoms to even teething. Yes. They get kind of fevers associated with it. Discomfort. Discomfort.

They won't sleep, so paracetamol, very effective. But interestingly, for pain, it tends to depend like how successful it is or useful it is for pain. It seems to depend on, one, what pain situation you're using it for and, two, the individual. So there's a bit of complexity here in the sense that there's some evidence out there that it's pretty crappy for pain

Yeah. It's pretty crappy for both acute and chronic back pain and not that great for arthritic pain. All right. But there's a low level of evidence to use it for things like headaches, post-surgical pain. And also in conjunction with other...

analgesics like codeine or morphine or things like that. Or even just in conjunction with NSAIDs. Right? So, yeah, interestingly, the pain one is... All right, we're going to go down a little bit of a rabbit hole here and just... Just about how it works. Yes. Okay. Because it's difficult. Yeah, we don't... Okay, well, to begin with, we don't know how it works. No,

Not completely. Not completely. We have ideas. Now, often people contrast and compare paracetamol with the NSAIDs, the non-steroidal anti-inflammatory drugs. We spoke about one aspirin previously, and we said that it works through the inhibition of Cox enzymes. And these enzymes synthesize prostaglandins, and prostaglandins are used all throughout the body to do many things,

You've got two major types of prostaglandins, broadly speaking. Those that are constitutively activated, which means they play housekeeping roles, maintain your gut mucosa, renal perfusion, blood pressure, and so forth. And then the others which are stimulated upon tissue damage. And these are the prostaglandins that stimulate inflammation, pain, fever, right? Now,

The thought originally was that paracetamol inhibited these COX enzymes as well. And then they started to realize that it doesn't really inhibit these COX enzymes.

However, there might be- At least peripherally. At least peripherally. That's the big one. And then they said, well, maybe there's a third Cox enzyme that inhibits. Because they thought, look, it has such similar effects to these NSAIDs that maybe it's inhibiting just another Cox enzyme and maybe somewhere else. And that's when they started to think about Cox 3. Yeah, because I think they found that it was a variant, a splice variant of Cox 1.

Within the central nervous system. So some of the experiments done, they found... So where it came to was we know downstream by the activation of the Cox enzymes, we're getting products known as prostaglandins, which could be things like PGE2 or PGI2. Now, peripherally, Panadol does not reduce those levels in your peripheral system. That means outside the central nervous system. But...

If you were to take paracetamol or close enough relatives of it, they found that somehow PGE2 is reduced in the central nervous system, brain spinal cord. So something is happening centrally,

for the reduction of prostaglandins within that system. Yeah, and it seems that the paracetamol's analgesic effects, which is to reduce pain, are largely independent of Cox inhibition. And we can talk about what mechanisms paracetamol leverages to reduce pain, but its antipyretic effects, its ability to reduce fever, might involve pain.

The COX enzymes and reducing PGE2. Because what we do know is that fever is regulated by pyrogens. So these are basically chemicals that stimulate... So either exogenous or endogenous. That's right. Mmm, I love ravioli. Oh, tanta fame. Since when do you speak Italian? Since we partnered with SAP Concur. Their integrated travel and expense platform and breakthrough solutions with AI gave me time back to dive into our financial future. We expand into Europe in 2027, so...

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And we may do an episode on fever in the near future, but just quickly chemicals can change the thermostat level of the hypothalamus. So instead of it setting it at 37 degrees Celsius, it can raise it up to say, Hey, I want the body to be a little bit hotter and cytokines and, um, uh,

are pyrogens that can do this, but the way they do this often is by playing around with PGE2, which is a prostaglandin.

in the central nervous system that boosts it up. And so fever is how it was discovered, the drug. Yeah, yeah. So yes, its ability to reduce fever might be through Cox inhibition centrally through the central nervous system, potentially through a Cox 3 maybe, but its ability to attenuate pain as an analgesic, we don't really know how it does it, but we've got some theories, some hypotheses. And also likely to be centrally inhibited.

Yes, yes, that's exactly right. So one of the main, it's probably not a hypothesis, we know that paracetamol can produce a metabolite called AM404.

And that's formed from paracetamol after it being decitylated in the liver into something called P-aminophenol. And that can cross the blood-brain barrier. And that's converted to something else called fatty acid amide, hydrolase, blah, blah, blah, blah, blah. But effectively, this AM404 is an active metabolite that seems- Like a radio station. That's right. Welcome to AM404. Whoa, hot dog. We have a wiener. What, what?

That's right, ladies. Okay. So, should we talk about how... I've got a couple of things here about how AM404 can reduce pain. Yep. You want me to jump in? Go for it. Okay. So...

We know that when it comes to nociception, the objective sensation of picking up nox, so the objective detection of noxious stimuli, things that can cause pain, we have certain receptors called TRIP receptors. TRIP-1s. That's right. TRP-V1 channels. And there's...

located peripherally and centrally. So AM404 is a potent activator of TRIP V1 receptors, which is interesting, but it is an activator of it in the central nervous system.

Now, TRIP-B1 receptors in the peripheral nervous system act differently to those in the central nervous system. So for example, sorry, not peripheral nervous system, just peripheral, so in the tissues of the body, right? So TRIP-B1 receptors

If you activate a TRIP receptor in your periphery, you've experienced pain. It transmits nociception. But if you activate it in the central nervous system, it suppresses the sensation of pain. And so AM404 seems to work centrally at activating the TRIP receptors, which ends up suppressing the nociceptive signal. So that's one bit of evidence that we have.

And we know this because studies showed reduced analgesic effects of paracetamol in TRPV1 knockout mice, so mice that no longer have TRPV1 receptors. That's right. It also seems to indirectly modulate calcium channels. And we know that if you throw calcium into a nociceptor, a neuron that carries a pain signal, that you experience pain. But if you stop this, then you can mitigate the transmission of that nociceptive signal.

Um, and AM404 seems to activate the cannabinoid receptors. And so the cannabinoid receptors are involved in, uh, the endocannabinoid. Oh, sorry. Well, yeah, basically that, that potential actually potentially there's a whole episode there. That's why you smoke your paracetamol, right? All right. Uh, editor we'll cut. Yeah. We'll cut that part. We'll cut that part. Uh,

There's also the paracetamol seems to increase serotonin, which is 5-HT. That's the chemical. Oh, okay. Yes. And that has a descendant modulating effect in the pain pathway too, right? Yes. That's the endogenous opioid system. So serotonin can suppress a nociceptive signal or quote unquote. Why would you want to do that?

Like, why would your body want to do that? Like just... Suppress a painful stimulation normally. Without any drugs. Yes, yes. Well, because this is the interesting thing about pain. Pain is a subjective experience. And often if we were to experience pain, it can be both physical and emotional and involves both aspects, plus social, if you want to get technical. If you have broken a bone...

and you're experiencing pain, that painful experience might be telling you, hey, avoid using that broken leg because we need to heal. But at the same time, your body doesn't need to constantly experience that pain. And in the moment...

If you're in a fight or flight situation, you might need to run away on a broken leg. Or just get out of that dangerous zone. So you could have a fight or flight triggering, which triggers both the noradrenaline and serotonin. The noradrenaline gives you the fight or flight, you know,

blood flow to the muscles, more oxygen, increased heart rate, all that sort of stuff that allows for you to fight or run away. But then the serotonin stimulation can make you not experience or reduce the pain. So at least in that moment, you can get away. And they all kind of all also act on the opioid system as well, don't they? Yeah, so adrenaline does as well. Adrenaline, serotonin. Particularly centrally, like in the brainstem, for example. Yeah.

So for example, if you watch football players, right? They go, at least if you're watching rugby, you'd watch the rugby. You see a bloke run headfirst into another bloke. His head is gashed open. Blood is just pouring from his eyebrow and he's just sitting there fine. They're stapling his eyebrow together. He seems absolutely fine. You would, but if right now in this situation, I were to knock you on the head with a brick to, to,

recapitulate that injury and then staple. You'd be in a lot of pain, but he's not noticeably showing the pain. And that's probably because he's in a war-like, you know, he's in his arena, his gladiatorial arena. So that's just the modulating pathway that we have intrinsically in our body. And what you're saying is the paracetamol potential analgesic effect is

Working in this system, maybe. Yeah, maybe. We don't definitively know, but we know that there's evidence that paracetamol increases serotonin levels. And the thought is that that contributes to the endogenous opioid system. So reducing or modulating an incoming pain signal or nociceptive signal. So it seems to be that...

The way that paracetamol suppresses pain is through a non-cox effect. And the way that it suppresses fever is through a cox effect. Right. Enzymes. And the cox would be centrally. If you're going to say that it has any kind of cox inhibition, it would be only in the central nervous system, not peripherally. Yeah, potentially in the hypothalamus itself. Yeah. Okay. So that's...

Basically the mechanism of action of the drug is

Do you want me to quickly give you the history of discovery? Yeah, absolutely. So it really came about serendipitously. That's not a word, is it? No, but that's okay. You could say serendipitously. That's what I was after. So this was in 1866 and there was a drug that was accidentally given for a patient that was being treated for an infection with intestinal worms. They were trying to give a drug, but they accidentally gave...

A different drug. This drug was acetylnyloid. And it's a white crystal drug. So instead of the kind of parasitic medication, they gave acetylnyloid. And what it did to the patient was their fever disappeared. Can I ask, what was that drug used for?

Why did they have that drug preparation? Yeah, I couldn't find that. Apparently what I came across that was similar in appearance. In those days it wouldn't have been, oh, here's your packet of tablets. It would have just been go into the chemical lab and there's

A jar of white powder. There's another one. We gave the wrong one. This was supposed to be for something else. Yeah. And I assume it wasn't locked away in a cabinet in which, you know, two nurses need to double check. That's right. That's right. The six rights. So what happened was the... Probably didn't help getting rid of the intestinal worms, but their fever disappeared. So they were like, wow, something's...

Working here, let's investigate this drug a little bit further. Now, unfortunately, the side effect of this drug was they developed cyanosis. Meaning? They went blue. Oh. So what happened was... Like Tobias of Arrested Development. Not quite. Not that blue? Not that blue. So what it did was...

caused a condition called methemoglobin, which basically changed the structure of the hemoglobin or the red blood cell. So it wasn't effective in carrying oxygen. So they were blue because they were cyanotic. That's right. Okay. Meaning didn't have enough oxygen. Yep. All right.

So they thought, well, there's something here, but we need to refine it if we want to use it as an anti-fever medication. So they started to play around with compounds related to that. They came to something called phenacetin, which was a close brother to paracetamol. Paracetamol was also thrown around the mix at this point as well. Again, the phenacetin was effective at the fever, but it...

caused mild hemolytic anemia, so red blood cells were still getting knocked off, and still some cyanosis. But then they kind of started to focus a little bit more on paracetamol, and then the turn of the 20th century, it became a more common medication. But they found in the 1940s, both that acetonilide and the phenacetin

It was actually the metabolic by-product that made it effective in its fever was actually paracetamol. Right. So they thought, let's just bypass. Right. So then paracetamol was first branded in 1956. There you go. And then from that point onwards, it's used as it currently is. Very cool. So it's been used...

You know how when aspirin was first discovered, it was used as an antipyretic, analgesic, anti-inflammatory? For a long time now, like thousands of years. Until we realized it's probably more useful as an antithrombotic, right, to reduce platelets. Paracetamol is not like that in the sense that we haven't discovered another use for it that is as useful or more useful, right? It's sort of been used as it was originally designed for as an antipyretic. Yeah, and analgesic, that's right.

So now we get to the kind of the point where it's the biggest or the most concerning aspect of paracetamol, which is its liver toxicity. Yes. So really quickly, I'll explain what's happening here. Usually when you take paracetamol, it's going to be metabolized by the liver. Now, the way that liver metabolizes it in, I think, two phase metabolic modification, it tries to make it more water soluble.

If you make a drug more water-soluble, it's easier to get rid of through the kidney. So the way that it does that, the liver, it adds a sugar group to it or a sulfide group to it. And so that is primarily paracetamol is modified to get rid of, particularly in therapeutic doses.

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However, there is a small degree that there are some enzymes in the liver that is different to those two enzymes group. And this is a cytochrome P450. But only a small percentage of paracetamol is used through this enzyme. But this enzyme...

Paracetamol into a long word. I'll attempt it. Good luck. Actually, I need to find it first because that's actually the name of it. Okay, here we go. So it converts it into N-acetyl-B-benzoquinone-imine. Right. Or easy to call it napki. Okay, so you're saying that the liver converts...

paracetamol into napki or can. Is that what you're saying? Yes, that's right. In small, small, small, small amounts. Now, napki is highly, highly toxic to the liver. Oh, okay. They're highly toxic. However, luckily, in the liver, we have a special molecule called glutathione that deactivates it quickly. So it kind of just turns it off. Because I think it's a...

It's an oxidant agent, so it causes free radical formation and toxicity to the liver. It's napki. Oh, yes, so glutathione can reduce that. That's right. Reduces that and turns it off. Yeah. So in therapeutic doses... That's fine. It's fine. The only problem is...

you either take too much of it, so if you overload the liver with too much paracetamol, so this would be the overdose amounts, you're going to toxicity, you've overloaded the enzymes that

that are trying to make it more water soluble. And therefore, more of the liver is going down the pathway, the cytochrome P450. Therefore, you're making more napki and you haven't got enough stores of glutathione to deactivate it. That's right. So now it starts building up and causes toxicity. Yes. And that's where the acute liver failure comes from. That's right. Now, there are some individuals that have lower glutathione levels

So the elderly are more prone because they have less reserves. Plus there are some genetic diseases where you just allow in that. So you may have to be careful with the amount of paracetamol you are taking. Well, I mean, this is the thing. It is a drug and...

just because it's available over the counter doesn't mean it's all safe, right? I think a lot of people go, oh, if I can get it over the counter, it means I can basically not get sick from it. I can take as much as I want. And obviously that is not true. The

And that's not true in anything. Like even if you went with vitamins. Yeah, that's right. You can have toxic overdoses. If you've got some spare time, watch Chubby Emu, the YouTube. He's great. And he goes through conditions of people who have

on a whole range of things. So there's people who... People say things like, I drank 100 energy drinks in 24 hours. This is what happened to my heart. That's right. That's sort of the... And so there's people who have overdosed in multivitamin gummy bears. Yes.

Yeah. Or zinc or something like that. So everything. Yes. What's the adage, you know, the famous saying, everything's poison, it's just a dose. That's right. That's right. Yeah. And again, don't be fooled by the fact that if some of something is good, more of something is better. That's, again, when it comes to, this is why you, I always think in medicine, the most important concept to understand is homeostasis, is that everything has a happy, healthy balance. Yeah.

Too little, not good. Too much, not good. So you need to find that happy, healthy balance. And that's why, same with everything. Bore is not better. So we know that...

It can cause liver toxicity if it's taken in too high dosage or taken for prolonged periods of time at a relatively high dosage. Well, you're still exceeding that kind of 24-hour maximum dosage amount. But also if you had...

Certain other medications could because, again, all medications are generally metabolized by the liver. So if there's other medications that you're taking that are depleting those glutathione stores, that could impact the toxicity. Or if it's just activating that cytochrome P450 enzyme, which makes more, let's say, more paracetamol is getting pushed in that pathway, that could be also problematic. Or if a person had...

liver injury already. They may have to be careful. It's a good point. It's a very good point that I don't think people realize is because your liver metabolizes probably most drugs that if you're already on... And not only drugs, going back to what we said with... Yeah, foods and stores. When you said about grapefruit, like that's one of the biggest interactor with metabolism because grapefruit juice, which just seems benign and innocuous, that has to be metabolized as well. Yeah, yeah.

Yeah. And so if your liver's already busy doing something, that it might get overwhelmed by having to do many things...

in a short period of time. And this does not mean, and I know that our listeners aren't necessarily the type of people who think this, but it's important. This does not mean, oh, I better take something to boost my liver's function. You can't. There's nothing out there that's going to make your liver more efficient. It doesn't work like that. The things that could make your liver more efficient is reducing alcohol intake and sleeping well and all those types of things.

But you can't improve your liver's function by taking something if you're already a relatively normal, healthy, happy person. Another point I want to highlight before we move towards the end of the episode is

I just want to talk a little bit more about people confusing paracetamol with NSAIDs. NSAIDs are defined as non-steroidal, so they don't use steroids, anti-inflammatory drugs. Their mechanism of action is to be anti-inflammatory. They stop the inflammatory process or processes, which include vasodilation, increased vascular permeability, swelling of tissues, pain,

heat, temperature, fever, all those types of things are associated with inflammation. Now, if you damage vascularized tissue, you'll get inflammation. So often trauma or infection can cause inflammation. And if you're experiencing pain or fever associated with it because as a result of inflammation, then an NSAID might be what's recommended to you by your healthcare provider, right?

But sometimes we can have a fever for unknown reason or pain and it could be viral, for example, and you could say, well, that's an infection and there might be some inflammation involved there. Very true. But often when it comes to reducing pain or fever due to known inflammation, the NSAIDs tend to be what's recommended first.

But however, again, there's caveats for everything. If you have pre-existing risks like gastrointestinal or renal, for example, then maybe NSAIDs won't be something that is prescribed to you. Maybe your healthcare provider will prescribe to you paracetamol, right? There are people who will...

have post... They'll go through surgery and they'll have post-operative pain. And there's a range of analgesics that can be given, but some people may not be able to handle the opioids. Opioids, right? So then they might be given NSAIDs, but then they might not be able to tolerate NSAIDs because they've got a pre-existing ulcer in their stomach or maybe they've already got pre-existing kidney disease or whatever. So then they might be given... So...

It's so complex, even though it might seem simple, that this is why you always need to seek God.

your advice from your healthcare provider. And again- Yeah, and they need to know your history. They need to know your history. So again, and I know I say it every episode, we are not telling you what to do and what not to do. We are not giving you advice as to what drug is better than another drug. We're simply providing you with an understanding as to what is the drug? What's its mechanism of action? What is the various adverse effects? Why is it used? Things like that. We are not here-

You shouldn't be listening to an episode going, I have X, Y or Z conditions. I'm going to listen to this episode to determine what drug I'm going to take next. Bad decision. We are not the people that you can or should be listening to for that advice. We are educators and that is it. And not very smart educators at that, to be honest, especially Matt. I make up for him. But...

Anything else you'd like to chuck in when it comes to acetaminophen or paracetamol? No, no, I think we've covered it. I think the main take-home point is...

It's a very effective drug. It's a very safe drug, but it does have its concerns in higher dosage. Generally, its side effect profile is very low, so it doesn't have the side effects that you would encounter with the other NSAIDs. But generally, it's a drug that's been created and been a very successful medication, safe medication, very useful medication. So we should be...

Pleased with its discovery and the fact that we have access to it today, but we have to be mindful and cautious with its use. Absolutely. Thank you. And we'll see you soon.

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