Speaker 1: On that September day, the postal worker picked his daughter up,
Speaker 1: as he often did, from preschool, at our lady of
Speaker 1: the wayside in the Chicago suburb of Arlington Heights, Illinois.
Speaker 1: They stopped at a nearby grocery store on the way home.
Speaker 1: Cassia always loved running errands with her dad. She wanted
Speaker 1: to go everywhere he did. She remembers walking with him
Speaker 1: down the aisles of jewel Osco that day. He picked
Speaker 1: out a bouquet of gladiolas for her mother. Cassia paused
Speaker 1: to point out a travel sized bottle of mouthwash. She
Speaker 1: loved how it fit in her hand so easily. That's
Speaker 1: when her dad picked up the bottle of extra strength Tylanol.
Speaker 1: They headed home together. She didn't know then it would
Speaker 1: be the last time.
Speaker 2: Oh, that's awful.
Speaker 3: It is it is so.
Speaker 1: That is from a CNN article titled Transformed by Tragedy
Speaker 1: by Catherine E. Schochet, published September twenty fourth, twenty twenty two.
Speaker 1: And that is about the tailand all murders, which we
Speaker 1: will chat about later in the episode. It is horrible. Yeah, yeah, Hi.
Speaker 1: I'm Aaron Welsh.
Speaker 2: And I'm Erin Allman.
Speaker 3: Updank and this is this podcast will kill You.
Speaker 2: And today we're talking about tilan all we are well
Speaker 2: because benefici paracetamol, the whatever, not to use the trade
Speaker 2: name or well it's It's also really difficult because I
Speaker 2: feel like there are like why are there two generic
Speaker 2: names for it? There are two official like chemical like
Speaker 2: short names for it, but why why Because two different
Speaker 2: people decided they wanted to name it, no joke, but like.
Speaker 1: Couldn't we come to a consensus, like for the coin,
Speaker 1: let's just know with I think mostly I use paracetamol
Speaker 1: in this.
Speaker 2: And I usually use the CEDAMNIFFM because that's what we
Speaker 2: call it in the US.
Speaker 1: Yeah, I don't know why I use paracetamol. I think
Speaker 1: it was the papers I read must have been UK
Speaker 1: based or something.
Speaker 3: You're at the post.
Speaker 2: It's good to know that paracetamol is the same thing,
Speaker 2: because it's definitely worldwide the more common term.
Speaker 3: Okay, that must be why it was in the papers too.
Speaker 2: Yeah, yeah, yeah, So a cedamniff in paracetamol today.
Speaker 1: Yeah, it's going to be a really interesting one and
Speaker 1: I can't wait to get to it. But first, it's
Speaker 1: quarantine any time, certainly is what are we drinking this week?
Speaker 1: We're drinking the chills Pills.
Speaker 3: Nice? Get it nice?
Speaker 1: Yeah? Pretty good is when you have chills, often a cedamtafin.
Speaker 1: Paracetamol is one of the drugs that you reach for.
Speaker 2: Yeah, and as we'll talk about, there might be other
Speaker 2: mechanisms by which it chills you out, but.
Speaker 3: I'm interesting, we'll get there.
Speaker 1: And the Chills Pills is based on a very classic
Speaker 1: cocktail called the Painkiller, which we also could have gone with,
Speaker 1: but like, I don't know, we wanted to put our
Speaker 1: own little spin on it.
Speaker 2: I suppose as we do.
Speaker 3: But it is a.
Speaker 1: Delicious set of ingredients. It has rum, pineapple juice, orange juice,
Speaker 1: cream of coconut. Pretty sure we haven't done this, but
Speaker 1: we've probably done something very similar.
Speaker 2: It's inevitable after six seasons. Yes, we'll post the full
Speaker 2: recipe for that quarantine, as well as our non alcoholic
Speaker 2: plusy Brita on our website, this podcast, wikill you dot Com,
Speaker 2: and all of our social media channels.
Speaker 1: We certainly will. On our website you can find all
Speaker 1: sorts of cool things, like the sources for each and
Speaker 1: every one of our episodes, transcripts, our bookshop dot Org
Speaker 1: affiliate account, our Goodreads list, merch music by Bloodmobile Patreon.
Speaker 3: So you check it out? Are you post it on
Speaker 3: our website? Actually? So, I'm just scrolling over the top. Men.
Speaker 2: You see your eyes like flicking back and forth. Those
Speaker 2: nice well done.
Speaker 1: I was like, Wow, finally I don't have to just
Speaker 1: like somehow bring this to the surface of.
Speaker 3: My brain to rank here. Anyway, check it out.
Speaker 2: It's great stuff, It's really great stuff. Well with that,
Speaker 2: shall we get into paracetamol aceta benefit.
Speaker 1: Let's do it right after this break.
Speaker 2: N acetyle para amino phenol.
Speaker 1: Huh oh, I'm already that's already too much.
Speaker 2: Well, then that's why they shortened it. It's aka acedamnifin,
Speaker 2: aka paracetamol. Both of those names are just literal shorthand
Speaker 2: for that chemical name and a style para amino phenol.
Speaker 2: Acetamnafin or paracetamol also in the literature, often called a
Speaker 2: pap aka brand name tailanol. In the US, I'll probably
Speaker 2: call it acetaminofin for most of this section, and it
Speaker 2: sounds like erin. You'll call it paracenamol, And both are
Speaker 2: entirely correct in pretty much every single paper I read,
Speaker 2: acetaminifin is cited as the most popular and widely used
Speaker 2: over the counter medication, possibly of any class, but certainly
Speaker 2: of analgesic anti pyretic medications, that is, pain relievers and
Speaker 2: fever reducers. And this is like worldwide, worldwide. Is true,
Speaker 2: it's a very common medication on its own, but it's
Speaker 2: also very common in combination medications. Like all of those
Speaker 2: coffin cold mixes that you buy, almost all of those
Speaker 2: have acetaminifin in them. Some studies suggest that nearly eighty
Speaker 2: percent of for example, the US general population use acetaminifin
Speaker 2: at some point in their lives, if not on the regular.
Speaker 2: And because of this, acetaminifin is also in many countries
Speaker 2: the most commonly used drug in intentional overdoses, as well
Speaker 2: as responsible for the most unintentional medication over in a
Speaker 2: lot of countries. And we'll talk about why that's so
Speaker 2: important in terms of the dangers of acetamenifin. But first,
Speaker 2: like what does it actually do? Like what what does
Speaker 2: the ceeda menafin do? What is it? What does it
Speaker 2: do to you? No one knows, That's what's the answer,
Speaker 2: as always on this podcast. So like I mentioned, it's
Speaker 2: bought and sold as an antipyretic meaning a fever lowering
Speaker 2: and an analgesic meaning pain reducing medication. So it reduces
Speaker 2: pain and it reduces our fever. And like you said,
Speaker 2: as it turns out, we don't fully know how it
Speaker 2: actually does this, and that fact alone still blows my mind.
Speaker 2: Like I knew that we didn't fully know the mechanisms
Speaker 2: of acetamenifin, but it was astounding to read so many
Speaker 2: papers about the potential theoretical mechanisms of this drug and
Speaker 2: have them all be like, so, just what we hypothesize
Speaker 2: on other people hypothesize this so well, who knows?
Speaker 1: It's like I feel like it's really interesting, and I
Speaker 1: think that when I tell you the origin story of
Speaker 1: acetum it might make a bit more sense. Why we
Speaker 1: don't know?
Speaker 2: Oh okay, I can't wait, it's gonna be fun. I
Speaker 2: know nothing except like, well, yeah, I know essentially nothing.
Speaker 2: So let's get into what we do know and what
Speaker 2: is hypothesized in the literature, shall we?
Speaker 3: Mm hm.
Speaker 2: The thing about pain that I will grant everyone trying
Speaker 2: to figure out the mechanisms of acetamenofin, and the thing
Speaker 2: about fever is that they're both a bit complicated to
Speaker 2: say the least, meaning it's not all just one mechanism
Speaker 2: to begin with. The other drug that we've talked about
Speaker 2: in detail on this podcast that has similar effects is aspirin.
Speaker 2: Aspirin is also a medicine that reduces pain and can
Speaker 2: be used as an antipyritic reduces temperature. In that episode,
Speaker 2: which was all the way back in season two, yeah right,
Speaker 2: yeah wow, I talked in detail about inflammation, the process
Speaker 2: of inflammation, the indicators of inflammation like redness, swelling, pain,
Speaker 2: and heat. And I talked in more detail than I
Speaker 2: realized about one of the main pathways that mediates inflammation,
Speaker 2: and this is something called the arachotonic acid pathway. I
Speaker 2: promise it's not going to be too heavy biochemistry in
Speaker 2: this episode, so please don't tune out. But I talked
Speaker 2: specifically about these enzymes called cyclooxygenase or cox enzymes, so
Speaker 2: to review that, because none of us remember, a racktonic
Speaker 2: acid is this substance that's present in all our cells.
Speaker 2: It's in our cell membranes and it is released when
Speaker 2: we have damage to our cells and then metabolized by
Speaker 2: cox enzymes into a whole bunch of different molecules like
Speaker 2: prostaglandins and leukotrienes and thromboxanes. These are different kinds of
Speaker 2: signaling molecules that induce inflammation, which again you'll have swelling
Speaker 2: and pain and heat things like that. Right when we
Speaker 2: have inflammation. En sids like aspirin and ibiprofen are what
Speaker 2: are called cocks blockers. But and in blocking these cox enzymes,
Speaker 2: they act as anti inflammatory medicines, and that is how
Speaker 2: they reduce pain and swelling and temperature. But pain is
Speaker 2: not just from inflammation, and neither is fever or rather
Speaker 2: our temperature regulation. Pain is incredibly complex and probably worthy
Speaker 2: of its entire own episode someday if we can figure out.
Speaker 3: How to do that.
Speaker 2: But I don't know how to do that. Yeah, But
Speaker 2: inflammation is just one potential cause of pain. There are
Speaker 2: a lot of other kinds of no susceptive pain, which
Speaker 2: is when we have pain from like an actual or
Speaker 2: a threatened like an almost damage to our tissue. That's
Speaker 2: called no susceptive pain. But you can also have neuropathic
Speaker 2: pain if you have damage to the nerves or what's
Speaker 2: called no subplastic pain, and this is from alterations in
Speaker 2: the way that we perceive pain, the way that pain
Speaker 2: signals are scent without any actual damage. And then we
Speaker 2: can also have mixed pain, like pain that comes from
Speaker 2: a lot of different sources. And our temperature regulation process
Speaker 2: is mostly mediated in our brain, but there are a
Speaker 2: lot of messengers and receptors that are involved in this process.
Speaker 2: So back to what we're actually talking about. Acetaminifin is
Speaker 2: not an end set. It's not like aspirin, like a coxblocker.
Speaker 2: It doesn't work directly by this Cox pathway, but it
Speaker 2: kind of works by that pathway. And the reason that
Speaker 2: I brought it all up is because we thought for
Speaker 2: a really long time that that is the way that
Speaker 2: it worked. So there is still confusion out there as
Speaker 2: to what the effects of thailanol are on inflammation. But
Speaker 2: as it turns out, thilanol doesn't affect our inflammatory pathways
Speaker 2: at all, and yet it still mediates both pain and fever,
Speaker 2: but by a different mechanism than things like iboprofen and aspirin,
Speaker 2: which is really cool.
Speaker 1: Are there other drugs that are similar to acedaminifin in
Speaker 1: that they also either reduce pain or fever, but also
Speaker 1: don't act as and SAIDs act.
Speaker 2: Yes, there are a lot of other medicines, especially for pain,
Speaker 2: that are going to act on entirely different parts of
Speaker 2: the system than things like iberprofen or aspirin when it
Speaker 2: comes to fever. I think there are at least a couple,
Speaker 2: but I'm not super familiar with them. Okay, yeah, so
Speaker 2: let's get into how thailanol actually does work, and then
Speaker 2: we'll learn a lot about some of these other ways
Speaker 2: that pain is kind of mediated. Besides inflammation, there are
Speaker 2: three main pathways by which acetaminifin probably we think exerts
Speaker 2: its effects, and one of them does in fact involve
Speaker 2: COX cyclooxygenase. So it was worth me telling you that
Speaker 2: whole story. So it turns out that we thought for
Speaker 2: a long time a cetaminifin worked very similarly to iberprofen
Speaker 2: just blocked this enzyme. It turns out, does do some
Speaker 2: COX blocking, but it's neither direct nor is it universal
Speaker 2: in our body. So rather than binding to this enzyme
Speaker 2: and blocking its activity, it seems more likely that aceenamtiphin
Speaker 2: what it does is reduce the active form of this enzyme,
Speaker 2: not like reduce the amount of it, but like oxidation reduction.
Speaker 2: Reaction donates some electrons and renders it inactive in that way.
Speaker 2: But and here's where it gets really fun and interesting.
Speaker 2: Acetamnafin seems to only do this in our central nervous system,
Speaker 2: not in all the cells in our body like most
Speaker 2: COX inhibitors.
Speaker 3: What the how I knew?
Speaker 2: You'd ask? Again. We hypothesize that it has to do
Speaker 2: with the levels of peroxide, because this is like an
Speaker 2: oxidation reduction reaction. It only works under certain conditions that
Speaker 2: are present the brain, but not in our peripheral tissues.
Speaker 1: Okay, So because it's not straight up blocking, it's just
Speaker 1: sort of interfering with this enzyme that the conditions have
Speaker 1: to be right. Okay, that's interesting and weird. And why
Speaker 1: aren't the conditions the same? Why are they different? What
Speaker 1: makes them different? What purpose does that difference serve?
Speaker 2: Those are two deep of biochemistry questions for me. But
Speaker 2: what I can tell you is that in doing this
Speaker 2: in our brain, the end result is that acetaminophin inhibits
Speaker 2: the production of prostaglandins, which are some of these molecules
Speaker 2: whose normal action is to increase our temperature and increase
Speaker 2: our sensitivity of pain receptors to various stimuli in our brain.
Speaker 2: So by blocking the production of prostaglandins, acetaminophin in our
Speaker 2: brain is reducing our temperature and reducing our sensation of pain.
Speaker 1: Fascinating Number one, I love it. Number two is it
Speaker 1: too early to ask about compare and contrast with end sets?
Speaker 3: And how like.
Speaker 1: Does aceta menafin work better than at these targeting proseglandins
Speaker 1: in your brain?
Speaker 3: Stuff like that?
Speaker 2: I love it, You know, I don't think that it's
Speaker 2: too early. We've got several more mechanisms to get through.
Speaker 3: We can just put a pin in it and come
Speaker 3: back if okay.
Speaker 2: Let's do that. We'll go through these and then ask
Speaker 2: me that again, because it's it is a really interesting question.
Speaker 3: Okay, okay, okay.
Speaker 2: But but there's more so another big mechanism by which
Speaker 2: acetamnifin seems to have an effect, and this one's really fun,
Speaker 2: also involves a rackadonic acid. That molecule that's released from
Speaker 2: our cell membranes. Turns out that a metabolite of acetaminifinn
Speaker 2: so binds up with a rackadonic acid and is then
Speaker 2: converted into something called AM four four N, a rackadinoil
Speaker 2: fenolamine huh, AM four O four it's easier. This molecule
Speaker 2: happens to be a weak but present agonist of our
Speaker 2: cannabinoid receptors in our brain, So this ends up leading
Speaker 2: to an increase in cannabinoids and has an effect on
Speaker 2: this other receptor that's related. Okay, what does that actually mean,
Speaker 2: I'm lost? Yeah, cannabinoids. Does that word sound familiar?
Speaker 1: Yeah?
Speaker 2: Sounds like cannabis. Yeah. Yeah. So cannabinoids are a group
Speaker 2: of substances, some of which are found in marijuana, cannabis,
Speaker 2: among other things. We have in our bodies and brains
Speaker 2: an entire system called the endocannabinoid system. We don't fully
Speaker 2: understand it or how it works. It's involved in a
Speaker 2: lot of different things. But some of the things that
Speaker 2: has been shown to be involved in, especially via a
Speaker 2: couple of specific receptors, is the perception of pain and
Speaker 2: our temperature regulation. Turns out that this molecule that acetamenifin
Speaker 2: can turn into in our brain AM four four acts
Speaker 2: on these receptors indirectly and increases the production of cannabinoids
Speaker 2: that interact with these systems and then mediates both pain
Speaker 2: and temperature in our brain. Through these receptors.
Speaker 1: Are these different hypotheses.
Speaker 2: Mutually exclusive, absolutely not, which is the most fascinating thing
Speaker 2: about them.
Speaker 1: Okay, So it could be through interfering with the production
Speaker 1: of prosseaglandins, or it could be by upregulating these cannabinoid
Speaker 1: receptor things.
Speaker 2: Yeah, but they're not mutually exclusive, so it's likely like
Speaker 2: all of this is happening at the same time the
Speaker 2: same time. Yeah, it's interacting with like a number of
Speaker 2: different receptors and enzymes in a number of different ways,
Speaker 2: which is probably why it's been so hard for us
Speaker 2: to pinpoint the exact mechanism if it's multifactorial, because there's
Speaker 2: one more okay, there has to be three, you know.
Speaker 2: Always acetaminefin seems to additionally activate again in our brain
Speaker 2: our descending inhibitory SARAH to nergic pathway. So many words,
Speaker 2: so much complication, but okay, let me simplify. When we
Speaker 2: have an injury or tissue damage or whatever, and pain
Speaker 2: is a result, that information of pain is transmitted from
Speaker 2: our skin or wherever that injury is through our spinal
Speaker 2: cord and through what's called the dorsal horn of our
Speaker 2: spinal cord and then up to our brain via these
Speaker 2: ascending pathways. Right, like skin, spinal cord brain, the pathway
Speaker 2: goes up. Then our brain has these other pathways that
Speaker 2: go back down through our spinal cord and then out
Speaker 2: to the periphery. These are called descending pathways. One of
Speaker 2: these descending pathways involves serotonin, which most people have probably
Speaker 2: heard of because of things like serotonin reuptake inhibitors or
Speaker 2: antidepressant medications. Serotonin is like a happy hormone, right. Serotonin
Speaker 2: via this pathway helps to mediate decrease the perception of pain. Right.
Speaker 2: So it's like our brain gets a signal, ah, we
Speaker 2: have pain, and it has these pathways to go. It's cool, man,
Speaker 2: we can deal with it. We don't have to feel
Speaker 2: the hurt. That's this very simplified way of looking at it.
Speaker 2: But by activating these inhibitory pathways, these serotonin pathways, acetamenafin
Speaker 2: likely has at least some small effect on the sensation
Speaker 2: of pain via these serotin pathways as well.
Speaker 1: So it like says, reassure this person even more that
Speaker 1: they're okay and they can handle this pain exactly okay.
Speaker 3: Interesting yeah, yeah right, interesting.
Speaker 2: I know That's why I said the chills pills thing
Speaker 2: works on so many different levels.
Speaker 3: Yeah right.
Speaker 2: It doesn't mean that tyl and ill's making everyone just
Speaker 2: feel really happy or anything. That's not how It's more
Speaker 2: complicated than that. But it's so many different little mechanisms
Speaker 2: that all of which are in our central nervous system,
Speaker 2: which I think is fascinating. So again, acidamenefin seems to
Speaker 2: pretty specifically affect pain via our central nervous system rather
Speaker 2: than peripherally or like directly at the sight of wherever
Speaker 2: that pain is coming from. And it's likely these multiple
Speaker 2: little mechanisms that all together produce the overall effect.
Speaker 1: Now, can I ask my question ages, please compare and
Speaker 1: contrast please with the following drugs, eprofen, aspirin. Those are
Speaker 1: the only two I can think of.
Speaker 2: You could even say opioids, opioids.
Speaker 3: There we go.
Speaker 2: Yeah. So, in general, acetaminefin is considered a very mild
Speaker 2: analgesic and a mild antipyritic, and mild really does seem
Speaker 2: to be the keyword. Most studies have shown it results
Speaker 2: in about like a point two two point four degree
Speaker 2: I believe that's fahrenheit decrease in human body temperature, which
Speaker 2: is even less than I would have thought based on
Speaker 2: my personal usage of it.
Speaker 3: Yeah, that's that seems really low.
Speaker 2: It's really minor. Yeah, it's a minor decrease in overall temperature,
Speaker 2: but it might be enough to make you feel a
Speaker 2: lot better Nutuh.
Speaker 3: Yeah.
Speaker 2: Yeah. Pain is something that's obviously very difficult to quantify
Speaker 2: and measure. But one thing that's interesting at least about
Speaker 2: the pain relieving effects of acetaminophin in comparison to end sense,
Speaker 2: is that it's not having any anti inflammatory activity. So
Speaker 2: if the pain is primarily and directly from the process
Speaker 2: of inflammation, it's generally not well treated with tailanol, and
Speaker 2: that's been shown in some studies. Things like rheumatoid conditions
Speaker 2: and things are not very well treated with something like acetaminifin.
Speaker 2: In some things like osteoarthritis, which is more of a
Speaker 2: direct pain rather than an inflammatory pain. Some studies have
Speaker 2: shown it's about equivalent or maybe a little less effective
Speaker 2: than something like n sets for that kind of purpose.
Speaker 2: So in general, it's considered pretty similar in terms of
Speaker 2: pain reduction to something like an ibiprofen. Okay, some studies
Speaker 2: show that it does fairly well at things like cancer pain,
Speaker 2: at least mild cancer pain, not severe cancer pain. And
Speaker 2: migraine headaches, though I feel like a lot of people
Speaker 2: with migraines would disagree with that, and is less good
Speaker 2: for things like tension headaches. So it's like very specific
Speaker 2: types of pain that it seems to be more effective
Speaker 2: versus less effective.
Speaker 1: Well, I would imagine that just person to person variation
Speaker 1: is probably pretty big.
Speaker 2: One thousand percent.
Speaker 1: Yes, yeah.
Speaker 3: Interesting.
Speaker 2: The other interesting thing is that because of the dominifin
Speaker 2: as a mild analgesic and a mild antipyretic is considered
Speaker 2: very similar to something like ibiprofen, which is another over
Speaker 2: the counter medication. Again is working via a different anti
Speaker 2: inflammatory pathway. Ibiprofen is an end said, a non steroidal
Speaker 2: anti inflammatory. They're very similar in terms of used to
Speaker 2: treat mild pain mild fevers. The difference often is cited
Speaker 2: as the risk of these two medicines, and depending on
Speaker 2: what paper you read and who you talk to, you
Speaker 2: might think that one is very risky and the other
Speaker 2: is not. But which one might be up in the
Speaker 2: air for a long time By a lot of people.
Speaker 2: Acetaminifin was considered very, very, very safe and safer compared
Speaker 2: to n sets. The reason for this is because n
Speaker 2: sets do have a significantly increased risk of GI side effects,
Speaker 2: specifically bleeding from the gastrointestinal tract, and that is because
Speaker 2: of their effects on cocks peripherally and in our stomach.
Speaker 2: That's a whole episode on its own, but it greatly
Speaker 2: does increase the risk of gastrointestinal bleeding more so than
Speaker 2: a seedaminifin. However, that's not to say that a cetaminifin
Speaker 2: is without risk. And so I think in recent years,
Speaker 2: as we've learned more and more about acetaminophin, the risk
Speaker 2: benefit calculus for some people and in some of the
Speaker 2: studies that I read, has perhaps shifted. And so especially
Speaker 2: if you're talking about short term versus long term use
Speaker 2: and degree of severity of the possible side effects, one
Speaker 2: could argue that a setaminifin might be more dangerous than
Speaker 2: hyberprofen and some people do argue that in the literature.
Speaker 2: So let's talk about the adverse effects of acetaminifin.
Speaker 1: Yeah, it's also it's interesting that I feel like sometimes
Speaker 1: the mechanism of a drug is figured out, at least
Speaker 1: in part by looking at adverse effects.
Speaker 2: Yeah, that's a good point.
Speaker 1: And so it's it's interesting that that doesn't seem to
Speaker 1: be the case with a seedaminifin.
Speaker 2: Yeah, not at all. Okay, Yeah, I don't know. It's
Speaker 2: a good question, So let's talk about it, shall we. Yeah,
Speaker 2: despite being so widely used, cannot overstate just how widely
Speaker 2: used a ceedaminifin paracetamol is worldwide. And despite it being
Speaker 2: considered in general a very safe medication that's used over
Speaker 2: the counter so frequently, it is incredibly toxic to the
Speaker 2: liver if too much is ingested. So how does this
Speaker 2: toxicity occur? If this medicine is super safe, and if
Speaker 2: all of the effects that I talked about with a
Speaker 2: ceedaminifin are in the brain, why is the liver involved
Speaker 2: all of a sudden, Well, our liver metabolizes acetaminafin unsurprising,
Speaker 2: our liver does that for most things, and the majority
Speaker 2: of a cedaminifin is metabolized in a way that produces
Speaker 2: the various substances that we talked about that cross into
Speaker 2: our blood brain barrier and exert their effects and help
Speaker 2: us feel better. Right, most of the way that our
Speaker 2: liver metabolizes a seedaminifin is all great, but our liver
Speaker 2: is complicated, and it actually has multiple pathways by which
Speaker 2: it metabolizes a seedaminifin. It's not just one and one
Speaker 2: of these pathways, which most papers I read say, accounts
Speaker 2: for about five to fifteen percent of the total metabolism
Speaker 2: of acetamenifin, uses one of our systems in our liver
Speaker 2: called the cytochrome P four fifty system, and this results
Speaker 2: in an incredibly toxic metabolite called nap qi. I'm not
Speaker 2: going to try and say the real name. And it
Speaker 2: turns out that this specific metabolite is really toxic to
Speaker 2: our liver cells. So when that is produced, it can
Speaker 2: then just kill off the liver cells right around where
Speaker 2: it's produced. Now, most of the time, we have enough
Speaker 2: of another molecule hanging out in our liver called glutathione
Speaker 2: that neutralizes this toxic metabolite, So no problem, we make
Speaker 2: a little bit of it, but we can neutralize it.
Speaker 2: But if this metabolite is produced in excess, say from
Speaker 2: too much a sedaminifin that we take too much at
Speaker 2: one time, we run out of this gluteithione, so then
Speaker 2: we can't neutralize this toxic napqi, and then this molecule
Speaker 2: literally starts killing our liver cells. And resulting in liver
Speaker 2: necrosis very bad.
Speaker 1: Is this why there are warning labels on acetamenifin products
Speaker 1: that are like do not take with alcohol or if
Speaker 1: you consume more than this number of alcoholic drinks today?
Speaker 2: Yes, because not only can chronic or high amounts of
Speaker 2: alcohol damage your liver, which can just affect the way
Speaker 2: that your liver metabolizes things. To begin with, alcohol also
Speaker 2: interacts with our cytochrome P four fifty system in a
Speaker 2: way that can directly alter the metabolism of acetaminifhin specifically
Speaker 2: as well. So do a number of other drugs, and
Speaker 2: so there's other drugs that have potential interactions with acetaminifin.
Speaker 2: But yes, that is the reason for those warnings. Okay,
Speaker 2: So when you have acetaminifin toxicity, there's kind of four
Speaker 2: stages of disease that you can have. First, probably unsurprisingly,
Speaker 2: since this is a medicine you're ingesting, you can have nausea, vomiting,
Speaker 2: maybe some stomach pain a lot of times though in
Speaker 2: the early stages people might be entirely asymptomatic. But then
Speaker 2: what we start to see in terms of lab numbers
Speaker 2: is that liver enzymes start to increase. These are a
Speaker 2: marker of liver damage, and this starts to show usually
Speaker 2: within twenty four hours, sometimes within twelve hours of ingestion,
Speaker 2: and then continue to increase over the next three to
Speaker 2: five days. And this can become so severe depending on
Speaker 2: how much acetamenefin was ingested, that it can progress to
Speaker 2: fulminent liver failure, complete liver failure, which can result in
Speaker 2: things like hepatic encephalopathy, which is when your brain begins
Speaker 2: to swell and not function because of all of the
Speaker 2: other things that are building up in your body because
Speaker 2: your liver has stopped working. We can see hyperbilirubinemia. This
Speaker 2: is an elevation in the breakdown products of our red
Speaker 2: blood cells that our liver is supposed to take care of.
Speaker 2: We can see lactic acidosis, or our blood becomes acidic.
Speaker 2: We can have profound hypoglycemia because our liver can't produce
Speaker 2: more glucose. You can have thrombocytopenia, so we're not able
Speaker 2: to make platelets, which can lead to bleeding, and then
Speaker 2: this can progress to shock and eventually death or the
Speaker 2: need for a liver transplant.
Speaker 1: And so the damage can happen or keep happening, or
Speaker 1: increase even after you stop taking a setamnifin.
Speaker 2: Yeah, we can see this kind of lag in maybe
Speaker 2: when those toxic metabolites had started to build up, and
Speaker 2: then when the liver is being the most affected, if
Speaker 2: that makes sense. On top of that, once our liver
Speaker 2: starts to fail and have severe liver damage, this can
Speaker 2: then cause additional damage to the kidneys what's called renal
Speaker 2: tubular necrosis. So we have now death of the cells
Speaker 2: lining the tubules of our kidneys because that's where acetaminifin
Speaker 2: and its metabolites are excreted. We pee out the metabolites
Speaker 2: of acetaminifin, So if these toxins build up, then it
Speaker 2: can end up affecting our kidneys as well. So this
Speaker 2: is obviously very severe and can and often is fatal
Speaker 2: if it's untreated. There is kind of an antidote, a
Speaker 2: treatment available. It's called n acetyl cysteine or KNACK, and
Speaker 2: it can prevent fulminent liver failure if it's given early enough.
Speaker 2: Early enough usually means within eight hours of ingestion, but
Speaker 2: it can also help prevent like complete liver failure even
Speaker 2: if it's given later than that, depending on how severe
Speaker 2: the damage has been to begin with. So the question
Speaker 2: really is how much does it take to do this right?
Speaker 2: Like how much does it take to have these severe
Speaker 2: side effects? And the answer to that question is why
Speaker 2: In more recent years, I think there has been a
Speaker 2: larger push I guess, or maybe chorus of papers that
Speaker 2: I found online saying maybe we should rethink how safe
Speaker 2: we consider acetam inifin most countries and most manufacturers list
Speaker 2: a maximum daily dose of a cetam in for adults,
Speaker 2: not talking about children as four grams. So as an example,
Speaker 2: extra strength tile and all that you can buy in
Speaker 2: the US is five hundred milligrams, So that's like taking
Speaker 2: two of those four times a day or every six
Speaker 2: hours in a twenty four hour period. And a lot
Speaker 2: of the older literature used to cite, based on data
Speaker 2: from intentional acute overdoses, that we don't see toxicity to
Speaker 2: the liver until we get to doses like ten or
Speaker 2: twelve grams, so you'd have to take quite a lot
Speaker 2: to overdose. But more recent data, especially data from people
Speaker 2: who perhaps weren't intentionally overdosing, but we're unintentionally taking slightly
Speaker 2: more than was recommended over the course of several days
Speaker 2: or a week, like maybe the time period in which
Speaker 2: you've got the flu. We have seen evidence of very
Speaker 2: severe hepatotoxicity or liver toxicity, including leading to death at
Speaker 2: much lower daily doses, like six or eight grams in
Speaker 2: twenty four hours, which is only a couple pills more
Speaker 2: than the maximum recommended dose. So I'm going to talk
Speaker 2: a little bit more about this in the current event
Speaker 2: section because I think it's one of the main stories
Speaker 2: with how we think about acetaminifin today. But this potentially
Speaker 2: small margin of error between the maximum daily recommended dose
Speaker 2: and a potentially incredibly toxic dose has become pretty controversial,
Speaker 2: especially because of how many other medicines acetamnafin can be
Speaker 2: found in that you may not know that acetamnafin is there,
Speaker 2: right right, So yeah, and that's all kind of just
Speaker 2: the acute toxicity in terms of chronic use. It also
Speaker 2: used to be thought that acetamnifin overall was much safer
Speaker 2: than other things like eybiprofen or n sids, aspirin, et cetera,
Speaker 2: because we know those definitely increase the risk of GI bleeding.
Speaker 2: Turns out it's a little more complicated because acetamenifin definitely
Speaker 2: has a significantly lower risk of GI bleed than en sids,
Speaker 2: but it's not non existent because there might be some
Speaker 2: peripheral COX activity going on, who knows. But there also
Speaker 2: is some mounting evidence that there's potential for other long
Speaker 2: term risks of large amounts of acetaminifin use over the
Speaker 2: long term, even if it's below that four gram threshold,
Speaker 2: and that is things like cardiovascular side effects, maybe a
Speaker 2: little increase in blood pressure. But in general, these data
Speaker 2: are not very well fleshed out at this point, which
Speaker 2: is really interesting considering how how long acetaminifin has been around,
Speaker 2: which I know you'll talk about. Yeah, interesting, it's very
Speaker 2: interesting in general, it is so, Yeah, that sounds very
Speaker 2: scary when it comes to acute, especially overdose of acetaminifin.
Speaker 2: I don't want to fear monger because this is a
Speaker 2: medication that we have a ton of data to show
Speaker 2: that when it's used as directed, which is below that
Speaker 2: four gram threshold for adults, or some countries have further
Speaker 2: reduced it to three grams just to like increase that
Speaker 2: margin of error, it does remain a very safe medication
Speaker 2: without this liver toxicity. Right.
Speaker 3: Yeah, So even though.
Speaker 2: Those numbers are not that much higher than what's recommended.
Speaker 2: They are higher than what is recommended. So yeah, anyways,
Speaker 2: that's a setum inefin paracetamol. And how it works, it's uh.
Speaker 1: It's mysterious and interesting.
Speaker 2: It remains so, doesn't it.
Speaker 3: Yeah, so tell me erin.
Speaker 2: How did we find it? How do we come up
Speaker 2: with it?
Speaker 3: Okay?
Speaker 2: How did we get here? Like where? We still don't
Speaker 2: know very much, and you know, tell me all the
Speaker 2: depressing things.
Speaker 1: Yeah, there, there is some of that, and I'll get
Speaker 1: to it all right after this break. The history of
Speaker 1: paracetamol slash acedamnifin slash tilotoll slash panadoll is a fascinating one.
Speaker 1: I'm sure there are more brand names out there I'm missing,
Speaker 1: and it's one that I want to tell in two
Speaker 1: main parts.
Speaker 2: Okay.
Speaker 1: The first is, of course, a history of discovery, of
Speaker 1: happy accidents and necessity acting as the mother of invention
Speaker 1: and all that jazz. The second is a tale of murder,
Speaker 1: of the shocking revelation that the public wasn't as safe
Speaker 1: as they thought, and the fallout from this horrific crime.
Speaker 1: Let's get started, Let's do it to help set the
Speaker 1: stage for the discovery of paracetamol. I'm going to ask
Speaker 1: you to cast your mind back to two very old episodes.
Speaker 1: Oh Malaria all the way back from our first season,
Speaker 1: and Aspirin from our second, which I know you.
Speaker 3: Revisited so I did her good to go, I'm there.
Speaker 1: And malaria because I want to talk about sinchona bark,
Speaker 1: which is where quinine is derived and which is used
Speaker 1: to treat malaria and other fevers. And aspirin because I
Speaker 1: want to talk about aspirin derived from willow bark and
Speaker 1: other plants and also used to treat fevers and pain.
Speaker 1: Full disclosure, I don't remember exactly how much I covered
Speaker 1: in either episode about this, but I'm going to talk
Speaker 1: for just a second about the enormous role that these
Speaker 1: two substances played in the development of the chemical and
Speaker 1: pharmaceutical industry in the nineteenth century. So, the plant sources
Speaker 1: of both quinine and aspirin had been used for hundreds
Speaker 1: of years to treat fevers and pain, but it wasn't
Speaker 1: until the first decades of the eighteen hundreds that the
Speaker 1: active compounds quinine and the glycoside of salcilic acid were isolated,
Speaker 1: and that was thanks to huge advancements in the field
Speaker 1: of chemistry, and what this meant, What this isolation of
Speaker 1: these chemicals meant was that the effects of these two
Speaker 1: compounds could be studied individually and in association with different dosages,
Speaker 1: and that they could be administered more accurately because you
Speaker 1: were giving a known amount of its pure form rather
Speaker 1: than a crude preparation. Because like the amount of quinine
Speaker 1: varies in different parts of the bark and from tree
Speaker 1: to tree and so on and so forth, so.
Speaker 2: You're like taking a medicine rather than just like chewing
Speaker 2: on the bark exactly.
Speaker 1: Yeah, And that's great news, right, Like having these extracts
Speaker 1: is awesome, except for the fact that getting enough of
Speaker 1: the source material, aka the plants to meet demand was
Speaker 1: a huge problem. Oh yeah, I bet and the British
Speaker 1: Empire especially wanted a ton of quinine to protect their
Speaker 1: office and administrators of tropical colonies from malaria. Quinine has
Speaker 1: been called one of the major tools of imperialism of
Speaker 1: the British Empire.
Speaker 2: I feel like I do remember you talking about that
Speaker 2: in the malaria episode.
Speaker 1: Yeah, I feel like there's so much more to that
Speaker 1: history of Sinchona bark and quinine that like I didn't cover.
Speaker 3: But anyway, look into it. It's really interesting.
Speaker 1: But this is just to show you that by the
Speaker 1: mid nineteenth century, the need for alternative painkillers or fever
Speaker 1: reducers was enormous, Like people just couldn't get enough of
Speaker 1: what would later be known as aspirin and quinine. Fortunately,
Speaker 1: improvements in technology and major intellectual advancements in all fields
Speaker 1: of science basically meant that the field of chemistry was
Speaker 1: up to this task. In this quest to find alternative
Speaker 1: painkillers or fever reducers, chemists first directed their focus towards
Speaker 1: extracting common pounds from natural sources, figuring that there had
Speaker 1: to be more plant parts like willow bark or sinchona
Speaker 1: bark that harbored potential drugs. But then with the birth
Speaker 1: and rise of industrial chemistry, chemists began to work on
Speaker 1: the synthetic production of drugs, mass producing compounds that they
Speaker 1: previously had to extract, or just creating new ones entirely.
Speaker 2: What an interesting time, I know.
Speaker 1: I you know, I feel like I have never really
Speaker 1: talked very much about or thought very much about the
Speaker 1: history of chemistry.
Speaker 3: But yeah, we should try to do more of that.
Speaker 2: I feel like you've alluded to it on several of
Speaker 2: our episodes, and it has always blown my mind every time.
Speaker 2: And so yeah, how do we do that little brainstorm?
Speaker 3: Will brainstorm? Yeah? Yeah, And because I.
Speaker 1: Have to mention germ theory, as I always do, even
Speaker 1: in an episode on paracetamol.
Speaker 2: Contractually required getting just kidding.
Speaker 1: When germ theory was introduced in the mid second half
Speaker 1: of the nineteenth century and malaria was shown to be
Speaker 1: caused by a parasitic organism and that quinine worked in
Speaker 1: part to actually attack the parasites, people began looking more
Speaker 1: towards chemical compounds to treat diseases and not just the
Speaker 1: symptoms of those.
Speaker 2: Diseases, right right, right, right right.
Speaker 1: So that does become relevant in a second here. Oh okay,
Speaker 1: but here's where the history I think gets a little
Speaker 1: bit chemical. So I'm just going to do the best
Speaker 1: that I can and taking us through without getting too
Speaker 1: bogged down in the IDEs or eins or whatever. And
Speaker 1: for those of you who want that more extensive thorough history,
Speaker 1: I'll post some great sources where you can get it.
Speaker 3: Okay.
Speaker 1: So in the eighteen eighties, a couple of young physicians,
Speaker 1: Con and Hept the University of Strasbourg had a patient
Speaker 1: come in with intestinal worms. They weren't sure how to
Speaker 1: get rid of the worms, so they went to their professor,
Speaker 1: who was the famous physician Adolf Kousmol to ask His advice.
Speaker 2: Was in kusma breathing. Wow.
Speaker 1: He suggested that they use something called naphthalene, which had
Speaker 1: been prescribed before as a quote unquote internal aniseptic. And
Speaker 1: so this is again trying to treat the worms. This
Speaker 1: is where the germ theory thing becomes relevant. They're like,
Speaker 1: we're going to try to eliminate these worms.
Speaker 2: Okay.
Speaker 1: They went to the pharmacy to get some of this
Speaker 1: naphthalene stuff, gave it to the patient, and were surprised
Speaker 1: to see their fever plummeted, which was not one of
Speaker 1: napthalene's known effects. So they were like, uh, what just happened.
Speaker 1: First of all, this is really weird. Why hasn't anyone
Speaker 1: described this before? This would be really great if we
Speaker 1: could use this as a fever reducer.
Speaker 3: Yeah.
Speaker 1: So then and they were like, all right, let's dig around,
Speaker 1: let's see like what's going on here, And they found
Speaker 1: out that the pharmacist had not in fact given them naphthaline,
Speaker 1: but rather something else entirely a compound called acid anilide
Speaker 1: that had not been used in medicine before ever, but
Speaker 1: was actually a byproduct of the organic dye industry. I sorry,
Speaker 1: don't know how what yeah what apparently that is where
Speaker 1: that's what acid analyide came from.
Speaker 2: But like, why was it at the pharmacy?
Speaker 3: I don't know.
Speaker 2: They were handing this out, They're like, it's cool, bro.
Speaker 1: What So maybe the pharmacist was more like a chemist
Speaker 1: in that sense, like you like it was wasn't just
Speaker 1: someone who only worked on medications but also just on
Speaker 1: chemicals more broadly speaking.
Speaker 2: So maybe they just like had that and by accident
Speaker 2: got it mixed up.
Speaker 3: Yeah.
Speaker 1: I think I think that that is my understanding.
Speaker 2: Oh my gosh, wow.
Speaker 1: Okay, yeah yeah, but I mean, like this story could
Speaker 1: have ended in so many other very differently, very very
Speaker 1: bad ways.
Speaker 2: Yeah. Yeah.
Speaker 1: But once the two physicians realized that not only did
Speaker 1: this acid analyde not poison people, but it was actually
Speaker 1: a super effective fever reducer, they were like, boom, we're
Speaker 1: marketing it and we're naming it antifebrin. Okay, So then
Speaker 1: they started selling it, okay, and this the success of
Speaker 1: this kicked off a ton of research into these types
Speaker 1: of compounds as potential fever and pain reducers, especially the
Speaker 1: search for ones that didn't cause some of the bad
Speaker 1: side effects that acid analyde had. So once it started
Speaker 1: to become more widely sold, people were finding that it
Speaker 1: interfered with hemoglobin's ability to carry oxygen in the blood,
Speaker 1: and so they were like, we kind of need something
Speaker 1: that doesn't do this.
Speaker 2: We kind of need to be able to carry oxygen.
Speaker 2: It's like a little importance to.
Speaker 1: Sah altitude sickness episode. But this boom and research also
Speaker 1: revealed that a metabolite of acid analyde, So a metabolite
Speaker 1: basically means something produced by the body after breaking down
Speaker 1: acid analyide that this metabolite might hold some promise. It
Speaker 1: was called paracetamol. Story over right, the end, the end, Yeah,
Speaker 1: that never is no. In eighteen ninety three, a world
Speaker 1: renowned clinical pharmacologist named Joseph von Mehring ran some trials
Speaker 1: on this metabolite, paracetamol, comparing its efficacy and safety with exacs,
Speaker 1: fever reducers or painkillers, and he was like, hey, this
Speaker 1: is great. Paracetamol reduces fever and pain, but it's actually
Speaker 1: just as dangerous as acid analyide. It also interferes with
Speaker 1: oxygen transport by hemoglobin. No one should sell it. It's
Speaker 1: not going to be a good replacement. Kind of weird, right,
Speaker 1: because we know that it doesn't do this right. And
Speaker 1: while yes, you talked about that it can be toxic
Speaker 1: in large amounts if not taken as instructed, von Mehring
Speaker 1: wasn't working with enormous doses, but like standard ones. So
Speaker 1: researchers today think that the paracetamol that he was using
Speaker 1: in these tests had been contaminated in some way, possibly
Speaker 1: with like acid analyide or one of the previous steps. Interesting,
Speaker 1: but von Mehring had such a strong reputation that no
Speaker 1: one questioned his results for fifty years. Fifty years.
Speaker 2: What had he done to be so well renowned? Man?
Speaker 3: I you know, I don't know.
Speaker 1: I also don't know if it was one of those
Speaker 1: things where they were like, oh, you know, this whole
Speaker 1: thing is toxic.
Speaker 3: Like how much interest was.
Speaker 1: There in acid analyide and paracetamol and so on?
Speaker 2: Yeah, that's so interesting.
Speaker 1: Yeah, people were like, oh, there must be other things
Speaker 1: that we could put our attention to. So I don't know,
Speaker 1: but yeah, fifty years. And I don't know what happened
Speaker 1: in the nineteen forties that prompted this, but around that
Speaker 1: time two researchers named Brody and Axelrod began a systematic
Speaker 1: study into paracetamol wow, and in nineteen forty eight they
Speaker 1: published a paper that outlined how paracetamol was actually the
Speaker 1: compound responsible for the fever reducing or pin reducing ability
Speaker 1: of acid analide, and importantly, it did not have the
Speaker 1: hemoglobin oxygen interfering effects that acid analyide had and that
Speaker 1: von Mehring was mistaken. Yeah, paracetamol also had some advantages
Speaker 1: over popular painkillers of the day. It could be given
Speaker 1: to kids as well as people with stomach ulcers, both
Speaker 1: for whom aspirin was a big no no. And Brody
Speaker 1: and Axelrod's papers on paracetamol were enough to convince the
Speaker 1: medical and scientific community that it was worth another shot
Speaker 1: and that it could and should be marketed, and so
Speaker 1: in the nineteen fifties it began to be sold, first
Speaker 1: generically in nineteen fifty three, and then as tailenol in
Speaker 1: the US in nineteen fifty five and as panadal in
Speaker 1: Britain in nineteen fifty six. So hopefully that wasn't too
Speaker 1: confusing of an origin story. But I just I feel
Speaker 1: like it is so amazing that we have this thing
Speaker 1: at all. Yeah, And I wonder whether this kind of bizarre,
Speaker 1: accidental so many things had to happen origin story may
Speaker 1: play a role in like why we still don't know,
Speaker 1: because like this thing was just here's this random chemical
Speaker 1: that somebody is getting and.
Speaker 2: Well, and then for it to be known used a
Speaker 2: little had someone say no, no, stop using it. Fifty
Speaker 2: years later, No, no, it's the safe version. Like that's
Speaker 2: a lot of like whiplash back and forth to then
Speaker 2: just be like, okay, cool, we're just we're using it. Yeah,
Speaker 2: let's not question it too hard or something.
Speaker 3: I don't know, right right. Yeah.
Speaker 1: And after this long and bizarre and kind of unexpected journey,
Speaker 1: once it was on the market, especially in the early years,
Speaker 1: it seemed like a really safe alternative to en SAIDs that,
Speaker 1: like I mentioned, we're increasingly becoming associate with ga ulceration
Speaker 1: and hemorrhage. But it wouldn't keep that super one hundred
Speaker 1: percent safe reputation for very long.
Speaker 3: In the nineteen sixties is.
Speaker 1: When reports of severe liver damage began to spring up
Speaker 1: in association primarily with intentional overdose, but the publicity of
Speaker 1: these reports did hurt the popularity of paracetamol for a while, which,
Speaker 1: like you talked about Aaron, is actually like quite a
Speaker 1: safe medication when taken properly. However, these reports were nothing
Speaker 1: compared to the infamous and heartbreaking tragedy surrounding thailanol in
Speaker 1: the early nineteen eighties. Yeah, introducing the tailanol murders. Before
Speaker 1: I get started, I want to give everyone a content
Speaker 1: warning here that I will be talking about the deaths
Speaker 1: of several individuals and you can skip ahead. I don't
Speaker 1: really know, but like maybe twenty five thirty minutes to
Speaker 1: be on the safe side if.
Speaker 2: You like not, you can always backtrack if you need.
Speaker 3: Yeah. Yeah.
Speaker 1: I also want to shout out the sources for this
Speaker 1: section right at the top here. I primarily used the
Speaker 1: online articles and podcasts produced by the Chicago Tribune. In
Speaker 1: September and October of twenty twenty two, investigative reporters Christy
Speaker 1: Getowski and Stacy Saint Clair did an amazing in depth
Speaker 1: review and investigation of this case and where we are
Speaker 1: today with it, and you should check it out for
Speaker 1: much more detail and much better storytelling than I'm about
Speaker 1: to do. The tail Nall Murders began on September twenty ninth,
Speaker 1: nineteen eighty two, a regular Wednesday morning for most of
Speaker 1: the residents of the suburbs around Chicago. Early that morning,
Speaker 1: at around six fifteen am, a twelve year old named
Speaker 1: Mary Kellerman woke up with a bad head cold. She
Speaker 1: convinced her dad to let her stay home from school
Speaker 1: that day and went into the bathroom to take a
Speaker 1: couple of extra strength tylan all that her mom had
Speaker 1: bought from the store the night before. Not more than
Speaker 1: a few seconds past when Mary's dad heard her coughing
Speaker 1: and then collapsing to the floor. He rushed in and
Speaker 1: found her on the ground, breathing shallowly and with her
Speaker 1: eyes fixed and dilated. He called the paramedics, but they
Speaker 1: weren't able to revive her. Mary's mom arrived home in
Speaker 1: time to see her only child being placed in an ambulance,
Speaker 1: and was held back from getting any closer to her.
Speaker 1: Mary was in full cardiac arrest even before reaching the hospital,
Speaker 1: and this happy, go lucky, inquisitive kind and so very
Speaker 1: loved twelve year old was pronounced dead at nine fifty
Speaker 1: six am. This was a nightmare, and it was only
Speaker 1: the beginning. That same morning, around eleven am, seven year
Speaker 1: old Adam Janis, resident of nearby Arlington Heights, was out
Speaker 1: running errands with his wife, Teresa and their young kids.
Speaker 1: This is the first hand account I mentioned. One of
Speaker 1: his stops was at a grocery store where he picked up,
Speaker 1: among other things, a bottle of extra strength tilanol. When
Speaker 1: he got home and put the groceries away, he opened
Speaker 1: the bottle of tailanol and swallowed a couple Within moments,
Speaker 1: he came out of the bathroom clutching his chest, breathing shallowly,
Speaker 1: and his wife saw that his eyes were fixed and dilated.
Speaker 3: Again.
Speaker 1: Paramedics were called, and again they couldn't do anything to
Speaker 1: save Adam. He was pronounced dead at the hospital at
Speaker 1: three point fifteen pm. No one knew what had killed
Speaker 1: him or Mary, but a massive heart attack was suspected
Speaker 1: in Adam's case, and the two deaths had yet to
Speaker 1: be linked. At three forty PM, a resident of nearby
Speaker 1: Chicagoland suburb Winfield named Mary Lynn Reiner, who was home
Speaker 1: with her six day old son Before feeding him, she
Speaker 1: took a couple of tilan All that she had bought
Speaker 1: earlier in the day to ease her headache. She began
Speaker 1: to feel dizzy and collapsed almost immediately, experiencing seizure. After seizure,
Speaker 1: she was also taken to a nearby hospital, where she
Speaker 1: was put on life support. She died the next day.
Speaker 1: Going back to the Janis family, who had gathered at
Speaker 1: the hospital where they were informed of Adam's death, Adam's wife, parents, sister, brothers,
Speaker 1: and their wives decided to gather back at Adam and
Speaker 1: Teresa's house to start planning his funeral. Adam's brother Stanley
Speaker 1: wanted to head back to his own house with his wife, Terry.
Speaker 1: They had just married three months ago. They hadn't even
Speaker 1: gotten the wedding pictures back yet because his back pain
Speaker 1: had started to flare up, but his mom convinced him
Speaker 1: to stay. When he and Terry got to Adam and
Speaker 1: Teresa's house, he said he was going to take a
Speaker 1: couple of tilan All for his back pain and headache
Speaker 1: and asked if anyone else wanted to. Everyone else said no,
Speaker 1: except for his wife, Terry, who also had a headache.
Speaker 1: He grabbed the bottle that he found in Adam and
Speaker 1: Teresa's bathroom, took two for himself and gave two to Terry.
Speaker 1: Within moments, both Stanley and Terry began complaining of chest
Speaker 1: pain and collapsed again. The paramedics were called, and they
Speaker 1: were shocked when the call came in because it was
Speaker 1: the exact same address as just a few hours before,
Speaker 1: and when they got there, it was like the most
Speaker 1: horrible deja vu. They found a frantic family huddled around
Speaker 1: Stanley and Terry, who were on the floor, breathing shallowly
Speaker 1: and with fixed and dilated eyes. What was happening? Remember,
Speaker 1: they thought that Adam might have had a massive heart attack,
Speaker 1: but it was next to impossible for two other young
Speaker 1: and healthy members of his family, one twenty five and
Speaker 1: one twenty to also have died of heart attacks within
Speaker 1: a few hours. Something was terrifyingly wrong. Oh yeah, sorry,
Speaker 1: I know that was a lot.
Speaker 3: There is there's more.
Speaker 2: Yeah, I have I mean, I have heard of this,
Speaker 2: but I don't think I've ever actually heard it all
Speaker 2: laid out side by side, and it's just, uh, it's
Speaker 2: really horrific.
Speaker 3: It is really horrific.
Speaker 1: And that's one thing that I kept feeling when I
Speaker 1: was when I was reading these articles or checking out
Speaker 1: the podcast, was just like this sensation of like terror,
Speaker 1: like to have this unfold throughout the course of a
Speaker 1: day and not know what was going on and be
Speaker 1: like where is this? How is this going to stop?
Speaker 1: Is this ever going to stop? And just like the
Speaker 1: absolute tragedy for the families, and.
Speaker 3: It's just it's just awful. Yeah.
Speaker 1: Yeah, I feel like in public health we often learned
Speaker 1: about it from like a this changed the way we
Speaker 1: package drugs, And I'm like, well, there's there's also like
Speaker 1: the lived experience of it too.
Speaker 2: That's I feel I don't know, yeah, which, and it's
Speaker 2: all of that is important, yeah yeah, yeah yeah but yeah,
Speaker 2: And so at this point it was obvious that something
Speaker 2: was really terrifyingly wrong, right, was it a deadly airborne
Speaker 2: pathogen or an environmental poison that's somehow people were exposed
Speaker 2: to because at.
Speaker 1: This point, right now, you know, only the Janice family
Speaker 1: is showing the like the link right, this is where
Speaker 1: the cluster is.
Speaker 3: That's like what is happening here?
Speaker 2: Right?
Speaker 3: The other cases have yet to be linked linked.
Speaker 2: Yeah, yeah, because it's all you mentioned, like different suburbs
Speaker 2: every day.
Speaker 3: Suburbs.
Speaker 1: Yeah, isolated cases, right, But and so, because this was
Speaker 1: happening within one family, the family, the Janis family, was
Speaker 1: rushed to the hospital to be put in an isolation room.
Speaker 2: Oh my gosh. Yeah.
Speaker 1: Can you imagine how terrifying that would be, like not
Speaker 1: knowing and while the family was in isolation, and while
Speaker 1: Stanley and Terry were fighting for their lives. In a
Speaker 1: town twenty miles away, a woman named Mary McFarland, whose
Speaker 1: single mother of two young boys, was at work with
Speaker 1: a headache. She grabbed a freshly purchased bottle of thailanol
Speaker 1: from her purse and took a couple of pills. You
Speaker 1: can guess what happened next. Moments later, she came back
Speaker 1: into the break room saying she didn't feel good and
Speaker 1: she collapsed. The paramedics, when they got there, attempted to
Speaker 1: revive her, and her friend mentioned the tilan al, but
Speaker 1: the doctors told Mary's family that they suspected a massive stroke.
Speaker 1: One more death would round out this horrifying day. Paula
Speaker 1: Prince's flight attendant for United stopped at a store after
Speaker 1: a long day of work and picked up a bottle
Speaker 1: of tailanol. When she got home, she took a single
Speaker 1: capsule from her new bottle while getting ready for bed,
Speaker 1: and her sister and friend found her body two days later.
Speaker 2: Oh No.
Speaker 1: Over the course of less than twenty four hours, seven people,
Speaker 1: Mary Kellerman, Adam Janis, Lynn Reiner, Stanley Janis, Terry Janis,
Speaker 1: Mary McFarland, and Paula Prince unsuspectingly swallowed tylan al pills
Speaker 1: that would kill them. When did people start to connect
Speaker 1: the dots? Turns out pretty quickly. After the paramedics were
Speaker 1: called to the Janis's house for the second time for
Speaker 1: Stanley and Terry, the fire department was also called because
Speaker 1: the situation was so unusual. Fire Lieutenant Chuck Kramer was
Speaker 1: one of the firefighters on the scene, and he suspected
Speaker 1: right away that something wasn't right, that these were not
Speaker 1: heart attacks, and that someone in public health should probably
Speaker 1: get involved as soon as possible, so he called his friend,
Speaker 1: the only public health official in the area, nurse Helen Jensen.
Speaker 1: She rushed to the hospital and started asking the Janis
Speaker 1: family about their day, what they had eaten, where they went,
Speaker 1: and she learned that all three of the people who
Speaker 1: had gotten sick had taken tailand al just moments before,
Speaker 1: so she then went to their house to see if
Speaker 1: she could spot anything. She looked around, found the bottle
Speaker 1: of tailan al, counted them all out and found that
Speaker 1: six were missing, two for each person who had gotten sick.
Speaker 1: Of course, no one believed her when she went back
Speaker 1: to the hospital and told a rep from the Cook
Speaker 1: County Medical Examiner's office that she thought the cases were
Speaker 1: linked to Thailand Al. She repeated herself several times, was
Speaker 1: met with skepticism each time and was like, you know what, Okay,
Speaker 1: I'm going home, But her friend fied. Lieutenant Chuck Kramer,
Speaker 1: who had called her initially, he had learned of her suspicions,
Speaker 1: and he told a friend of his, another fire Lieutenant
Speaker 1: Phil Capitelli, who mentioned that Mary Kellerman, the twelve year
Speaker 1: old who died, had also taken tylnal moments before collapsing.
Speaker 1: That seemed like too much of a coincidence to Kramer,
Speaker 1: who called the hospital where the Janices were and told
Speaker 1: their doctor, Thomas Kim, what he had found out. Doctor
Speaker 1: Kim was interested and had already suspected that the Janises
Speaker 1: had ingested some sort of poison, but this didn't seem
Speaker 1: like the other cases of paracetamol poisoning that he had
Speaker 1: treated in the past. For one, the symptoms were wildly different,
Speaker 1: and for two, paracetamol poisoning took much longer to show.
Speaker 1: There was only one poison he could think of that
Speaker 1: caused death so quickly after ingestion, cyanide.
Speaker 3: Yeah.
Speaker 1: He ordered cyanide tests to be done on blood from
Speaker 1: Stanley and Terry, And meanwhile, a police officer picked up
Speaker 1: the bottle of Tile and All from the Janice house
Speaker 1: and brought it to the hospital. The Deputy Chief Medical
Speaker 1: Examiner told his investigator, who was at the hospital, to
Speaker 1: take a whiff inside the bottle like just saw which
Speaker 1: kept not a good idea necessarily, but what he smelled
Speaker 1: was bitter almonds, which is the signature scent of cyanide.
Speaker 1: But also apparently I read that only sixty percent of
Speaker 1: the population can even smell it, So like, whoa pretty
Speaker 1: amazing yeah. Yeah, And the blood tests from Stanley and
Speaker 1: Terry came back at one point thirty in the morning,
Speaker 1: and they showed an incredible amount of cyanide, certainly the
Speaker 1: cause of death. Later analysis would show that each pill
Speaker 1: in the Janis's bottle had an amount of cyanide three
Speaker 1: times what would take to kill someone.
Speaker 3: What each pill?
Speaker 2: Each pill?
Speaker 3: Yeah.
Speaker 1: The news of the cyanide laced tailand All pills didn't
Speaker 1: break in time to be included in the next morning's newspapers,
Speaker 1: but it was broadcast on local TV, and police and
Speaker 1: public health officials went around door to door, posting flyers
Speaker 1: warning about the pills, ordering stores to pull it from shelves,
Speaker 1: and driving around using bullhorns to announce like, hey, if
Speaker 1: you bought tailan All, throw it away? Whoa yeah, And amazingly,
Speaker 1: probably due to what seems like an incredible speed with
Speaker 1: which this medical mystery was solved, no other deaths occurred
Speaker 1: from the tainted bottles, and at least three other bottles
Speaker 1: were found, but it's likely there were more because so
Speaker 1: many people just simply threw them away.
Speaker 2: That was going to be my question is did they
Speaker 2: find any other bottles?
Speaker 1: They did, Yeah, they found a handful more, only three,
Speaker 1: but like, yeah, wow, likely there were more out there,
Speaker 1: and these tainted bottles had been sold from grocery stores
Speaker 1: all around the Chicago Land area.
Speaker 2: Is so I think that's one of the weirdest parts.
Speaker 1: Yeah, like the wide distribution of them, and how it
Speaker 1: all happened like so fast.
Speaker 2: And lay all at the same time. Yeah, like what
Speaker 2: that's what? Yeah?
Speaker 3: Yeah, it's yeah.
Speaker 1: And also I think that that is sort of what
Speaker 1: helped contribute in some way to both confusion initially but
Speaker 1: also figuring out what was actually going on, because it
Speaker 1: wasn't immediately clear whether these bottles had been tampered with
Speaker 1: or contaminated sometime during the manufacturing process, in which case
Speaker 1: like whoa, we may have a nationwide problem, or did
Speaker 1: someone slip the cyanide tainted bottles onto the shelves in
Speaker 1: these stores later on?
Speaker 3: Right, And just in.
Speaker 1: Case it was the former that it was a manufacturing contamination,
Speaker 1: Johnson and Johnson, who produced tilanol, halted production, issued recalls,
Speaker 1: stopped advertising, and sent out like tons and tons of warnings.
Speaker 1: But when it was found that the bottles were from
Speaker 1: different lots entirely, it seemed much more likely that there
Speaker 1: was like an individual or a couple individuals that did this. Right,
Speaker 1: how how do they do this? How simple? Like disturbingly simple. Today,
Speaker 1: when you buy a new bottle of thilenol or any
Speaker 1: other over the counter medication or anything, really it comes
Speaker 1: in tamper proof packaging in a sealed paper box, plastic
Speaker 1: wrapped lid, foil, seal over the top, several things that
Speaker 1: would make it apparent if someone else had opened the
Speaker 1: bottle before you. Back in nineteen eighty two, that type
Speaker 1: of packaging did not exist yet. You could say, buy
Speaker 1: a couple of bottles of extra strength tile and all
Speaker 1: bring them home, take them out of the non glued box,
Speaker 1: unscrewed the cap, replace the acedum in afin inside the
Speaker 1: capsules with cyanide, put them back in the bottles, screw
Speaker 1: the cap back on, put the bottles back in those boxes,
Speaker 1: and then just walk into the store and put them
Speaker 1: back on the shelf without anyone realizing.
Speaker 2: Oh wow, the eighties.
Speaker 1: It's yeah, wow, it's kind of hard, like I think
Speaker 1: from our perspective today with literally everything that is, yeah,
Speaker 1: tamperproof packaging hard to imagine.
Speaker 2: Like mustard, like yeah, everything.
Speaker 1: Yeah, it's kind of like a loss of innocence in
Speaker 1: a way, like it's like oh wow, yeah, I don't know,
Speaker 1: it's just it seems very shocking, yeah that that was
Speaker 1: not something that you did immediately.
Speaker 2: But then when you when you think about it, it's like, oh,
Speaker 2: it's so sad that all of our everything we buy
Speaker 2: has to be like that because because people will will
Speaker 2: murder people. Yeah.
Speaker 1: Yeah.
Speaker 2: For example, as an example, not just like take a
Speaker 2: few pills, you know, like then you're getting less than
Speaker 2: you paid for or something. It's like, oh, no, we
Speaker 2: replaced all the pills with cyanide.
Speaker 3: What right?
Speaker 1: Yeah, so what the heck? Yeah, great question. Investigators knew
Speaker 1: pretty soon after the murders happened what had killed these
Speaker 1: people and how they had gotten exposed, which, honestly, like
Speaker 1: it's still I think is so amazing how fast that
Speaker 1: was solved. And I think in large part it's because
Speaker 1: the Janice family and how it was like, Okay, what
Speaker 1: is the commonality among these three individuals, and then but
Speaker 1: also like this fire lieutenant talking to this fire lieutenant
Speaker 1: calling this particular nurse who just like had that like
Speaker 1: detective work down. It's just amazing that.
Speaker 2: I think that's my favorite part is that not not
Speaker 2: only did the fire lieutenant call his buddy, but that
Speaker 2: person also had heard about the tile and all with
Speaker 2: the other person. And so then how many other fire
Speaker 2: chiefs did they call or like whoever it was that
Speaker 2: they called from the other suburbs and places like I mean,
Speaker 2: because all of these would have been very like dramatic
Speaker 2: at whatever hospital these people presented to, right, But it's
Speaker 2: still very amazing that that that information got passed around
Speaker 2: so rapidly to be able to identify all of these
Speaker 2: and then really pinpoint it so that you could get
Speaker 2: the word out everywhere and not just in the one neighborhood.
Speaker 1: Right, And and you know, different hospitals were involved in this, yeah,
Speaker 1: and then you have the doc going, oh, I think
Speaker 1: it's cyanide like, right, it's so amazing, and then all
Speaker 1: within twenty four hours, and so the number of lives
Speaker 1: I feel like that were saved. I mean, I think
Speaker 1: it's absolutely horrible that seven people lost their lives, but
Speaker 1: it's also like you could imagine how if it hadn't
Speaker 1: been solved so quickly, there could have been so many more.
Speaker 1: Ough it's just yeah, but yeah, So even though they
Speaker 1: figured this out so quickly, there were two big questions
Speaker 1: that remained.
Speaker 3: Who and why? Yeah.
Speaker 1: The short answer is, like the mechanism of a cudamnifin paracetamol,
Speaker 1: we don't know. Oh No, to this day, no one
Speaker 1: has been charged for these murders. There are a few
Speaker 1: notable suspects, one in particular, and the Chicago Tribune series
Speaker 1: is excellent if you want to get all the detail
Speaker 1: hills about who investigators suspected and why there's like a hole,
Speaker 1: it's really good. And I'll just briefly tell you about
Speaker 1: one of them that seems like the prime suspect and
Speaker 1: some of the reasons why he is.
Speaker 2: So.
Speaker 1: A week after the murders, Johnson and Johnson Headquarters received
Speaker 1: a letter saying, if you want to stop the killing,
Speaker 1: wire one million dollars to this bank account. The letter
Speaker 1: was traced to a thirty six year old man named
Speaker 1: Jim Lewis, who had ties to the Chicagoland area. At first,
Speaker 1: investigators thought that he was probably just an opportunist trying
Speaker 1: to profit off of these deaths, but they dug a
Speaker 1: little deeper and found that he had been charged in
Speaker 1: but not convicted, of a murder in Kansas City four
Speaker 1: years prior, showing that he was potentially capable of violence,
Speaker 1: and he was currently under investigation for a credit card scam.
Speaker 1: He was tried for extortion, and while he awaited sent
Speaker 1: and sing he reached out. Jim Lewis reached out to
Speaker 1: an FBI agent on the case and offered his expertise,
Speaker 1: drawing detailed sketch after detailed sketch of the logistics of
Speaker 1: poisoning the capsules, like how you would go into this
Speaker 1: store versus this store, And how you would empty out
Speaker 1: the aceta minifin with cyanide and replace it with cyanide,
Speaker 1: and all of these things, and like troubleshooting, what would
Speaker 1: happen if something went wrong? What would you do in
Speaker 1: this case versus this case? He wanted to read all
Speaker 1: the case files, like get really involved, A little bit suspect, right, circumstantial,
Speaker 1: but anyway. Ultimately, Lewis was sentenced to ten years in
Speaker 1: prison for the extortion letter, plus time for the credit
Speaker 1: card scam, and when he was released in nineteen ninety five,
Speaker 1: the FBI still had him in mind for the murders,
Speaker 1: continuing to monitor him and even running an undercover sting
Speaker 1: in two thousand and seven where an agent posed as
Speaker 1: someone writing a book about the murders and offering to
Speaker 1: clear his name. They collected lots of strong circumstantial evidence
Speaker 1: against Lewis for one motive. So he had a young
Speaker 1: daughter named Tony who died after a heart surgery her second,
Speaker 1: and an autopsy revealed that the sutures that had been
Speaker 1: used in her first heart surgery were made by Johnson,
Speaker 1: and Johnson possibly faulty, possibly contributing to her death during
Speaker 1: the second heart surgery. So maybe investigators thought that he
Speaker 1: wanted to take revenge on the company in this way.
Speaker 1: Number two is that he allegedly wanted to start a
Speaker 1: pill press business, like making pills. Number three, his timeline
Speaker 1: for being out of town and writing the letter kind
Speaker 1: of changed, so like he definitely wrote the letter, but
Speaker 1: he like when.
Speaker 3: Was it sent?
Speaker 1: Was it sent before the pills were placed on the
Speaker 1: shelves or before the news broke? Like how did that
Speaker 1: all sort of come into play? And that sort of
Speaker 1: is in question. But how much of that is like
Speaker 1: just incorrect recall, and you know, forty years have passed,
Speaker 1: I don't know, But there's been a lot of DNA
Speaker 1: testing in recent years of the bottles that are still
Speaker 1: in evidence or whatever, and none of them have linked
Speaker 1: him physically to the pills. And the investigation is still
Speaker 1: ongoing currently.
Speaker 2: Wow.
Speaker 1: Wow, Yeah, there's so much more to that case. Like
Speaker 1: really most I feel like most of what I talk
Speaker 1: about is like the first article and then like snippets
Speaker 1: of like each of the later ones. Wow, but yeah,
Speaker 1: but the title it all. Murders prompted huge changes both
Speaker 1: in the way pharmaceuticals and other products are packaged, as
Speaker 1: well as it disrupted the sense of safety or trust
Speaker 1: that the public had in these products. Two months after
Speaker 1: the murders, tamperproof packaging was introduced, and in nineteen eighty
Speaker 1: three it became a federal offense to tamper with consumer products.
Speaker 1: By nineteen eighty nine, the FDA introduced guidelines for all
Speaker 1: consumer products to have tamperproof packaging. Still, it took a
Speaker 1: long time for the public to trust tilanol and other
Speaker 1: medications again. And one of the sort of like searing
Speaker 1: things I think about this story about these cases is
Speaker 1: the horror of it all. Right, Like these these people's
Speaker 1: lives were just ripped away from them, like within moments,
Speaker 1: who were just completely out of the blue doing nothing
Speaker 1: and then one day attacked for no reason whatsoever, and
Speaker 1: then just like that was it. It's done, And it
Speaker 1: just feels like such a senseless and horrible thing. And
Speaker 1: I think the horror of it all and how scary
Speaker 1: and how this was able to happen is really you
Speaker 1: can see that in just how rapidly things changed and
Speaker 1: how much things changed in terms of like it is really,
Speaker 1: I mean, there was a before and after very starkly
Speaker 1: different in terms of like tamper proof packaging, how we
Speaker 1: approach that, how we view safety in stores, protections for consumers.
Speaker 1: And it is horrible that these deaths had to spur
Speaker 1: that on. And it's also horrible that their family members
Speaker 1: and their friends and their loved ones still don't have
Speaker 1: the resolution and closure in the form of justice.
Speaker 2: Yeah, it is remarkable how this one incident, in being
Speaker 2: so terrifying and horrific, literally changed not just an entire industry,
Speaker 2: but like how all consumer goods are packaged and how
Speaker 2: we view consumer safety in that way.
Speaker 3: That's it's massive, it really is.
Speaker 1: And I think there was at least something I read
Speaker 1: that suggested that the tilt All murders actually sort of
Speaker 1: inspired or fueled the fear surrounding Halloween candy in the
Speaker 1: early nineteen.
Speaker 3: Eighties, particularly that year, where they were.
Speaker 1: Like, oh, Halloween candy is poisoned, it's tainted, blah blah blah, wow,
Speaker 1: which is like, well, you're just yeah, so.
Speaker 3: Anyway, oh wow yeah.
Speaker 1: Okay, Well with that Aaron True Crime podcast over and
Speaker 1: back to science podcast.
Speaker 3: I'll turn it over to you to fill us in
Speaker 3: on where we are with tilin all today.
Speaker 2: Okay, we'll take a quick break and I'll do my best. So,
Speaker 2: like I said at the top, acetaminifin paracetamol remains one of,
Speaker 2: if not the most widely used over the counter medications worldwide,
Speaker 2: especially of analgesic anti poetics like pain reliever, fever reducer medication.
Speaker 2: It also, in many countries is one of the most
Speaker 2: common causes of both intentional and unintentional overdose admissions to hospitals,
Speaker 2: and in the US and the UK and Europe, one
Speaker 2: of the most common causes of acute liver failure as well.
Speaker 2: I could not get solid data on the exact number
Speaker 2: of overdoses or deaths, or even liver transplants that are
Speaker 2: due to acetominifin toxicity worldwide. Most sources that I read
Speaker 2: for the US data cited about fifty six thousand overdoses
Speaker 2: that result in emergency department visits and up to five
Speaker 2: hundred deaths annually in the US, But from what I
Speaker 2: can tell, that's data from like two thousand and five
Speaker 2: that's just still cited everywhere, so I don't know if
Speaker 2: there's more up to date data, and it seems like
Speaker 2: that might not be the most accurate because some of
Speaker 2: the numbers that I saw from the UK are quite
Speaker 2: significantly higher in terms of overdoses, like eighty to ninety
Speaker 2: thousand hospitalizations but between one hundred and fifty two hundred deaths.
Speaker 2: And obviously our population sizes are very different, so it's
Speaker 2: really hard to say how many people this is affecting worldwide,
Speaker 2: but certainly it's not an insignificant number of people that
Speaker 2: are becoming very sick or potentially dying from liver toxicity
Speaker 2: associated with the setominifin. However, there's also tens of millions
Speaker 2: of doses that are taken every single day across the globe.
Speaker 2: This is an incredibly ubiquitous medication. So again, this is
Speaker 2: something that when taken in the dosages that are recommended
Speaker 2: or below the maximum recommended doses, is quite safe. But
Speaker 2: I think that this idea of how do we determine
Speaker 2: what is safe and what a maximum dose should be,
Speaker 2: and how do we label medications and package medications to
Speaker 2: let people know what is safe and what is potentially
Speaker 2: dangerous about them. Is kind of where the story of
Speaker 2: a cetamnifin or paracetamol is going and is likely to
Speaker 2: continue to go in the future. There was a really comprehensive,
Speaker 2: very very very long article published by pro Publica from
Speaker 2: twenty thirteen, so it's fairly old now, but I found
Speaker 2: it really interesting because it really focused on the pushback
Speaker 2: from manufacturers on changing anything about the way that we
Speaker 2: label a cetamnifin to let people know that it is
Speaker 2: potentially toxic and specifically what that toxicity might look like.
Speaker 2: Because a cetamenifin toxicity because it can build up over
Speaker 2: several days, you might not know that it's happening while
Speaker 2: it's happening, so it could be asymptomatic, right, And there's
Speaker 2: been a lot of push push back or laxity from
Speaker 2: like the FDA in terms of implementing stricter safety measures,
Speaker 2: which we've seen implemented in other countries like the UK,
Speaker 2: which has much stricter requirements on how many pills can
Speaker 2: be in a package and things like that, with mixed
Speaker 2: results on whether that's actually decreased overdoses overall, but at
Speaker 2: least there's like public health attempts, if that makes sense.
Speaker 2: So I think that that's kind of an important part
Speaker 2: of the estate of benefit story is really not only
Speaker 2: understanding the mechanisms, like how is this really working in
Speaker 2: our bodies? Are there other like chronic effects that we
Speaker 2: might not be aware of that are happening or are
Speaker 2: they only happening at very high doses? How do we
Speaker 2: label this medicine that's so ubiquitous, right, It's in so
Speaker 2: many of our other like mixed formula drugs that are
Speaker 2: available over the counter and in some cases in relatively
Speaker 2: high quantities that you might not realize altogether add up
Speaker 2: to more than four grams? Are there other public health
Speaker 2: measures that could be implemented that would reduce the risk
Speaker 2: of unintentional overdoses, especially as well as intentional overdoses. So
Speaker 2: I think that that's kind of where the future of
Speaker 2: acetaminifin research and public health is likely going to go.
Speaker 2: And I think for me, what it really highlights is
Speaker 2: something that we've talked about actually kind of a lot
Speaker 2: on this podcast, and that is that the dose makes
Speaker 2: the poison right, Yes, literally nothing no medication, antibiotics, anti fever,
Speaker 2: pain medication, gas, medication, constipation, medication, any medicine, any drug,
Speaker 2: any thing that you consume or put into your body
Speaker 2: has pros and cons It has the potential to help
Speaker 2: us and has the potential to have undesirable side effects.
Speaker 2: And so all of medicine is balancing these and making
Speaker 2: sure that the benefits outweigh the real or potential harms.
Speaker 2: And so I think that maybe for acetaminifin that there's
Speaker 2: been a long period of just focusing on all of
Speaker 2: the benefits and the fact that it is safer than
Speaker 2: en SAIDs in certain respects. It is safer than end
Speaker 2: SAIDs in terms of risk of GI side effects or
Speaker 2: even kidney side effects, but that doesn't mean that it's
Speaker 2: without its potential for very serious harm. And so how
Speaker 2: do we then balance that both on an individual level
Speaker 2: and also on a population level from a public health perspective. Yeah, yeah,
Speaker 2: So that's paraceta, all acetominifits sources.
Speaker 1: Okay, for I have several for like the history of
Speaker 1: acidamnifin paracetamol, I'll shout out one in particular by Bruna
Speaker 1: at All from twenty fourteen called acidamnifin paracetamol A history
Speaker 1: of errors failures and false decisions. Oh, I read that one,
Speaker 1: and then again I'll shout out just the amazing series
Speaker 1: by Chicago Tribune on the Thailand All Murders. The podcast
Speaker 1: I will shout out specifically is called Unsealed the Thailand
Speaker 1: All Murders.
Speaker 2: I had quite a number of papers for this episode,
Speaker 2: most of which focus on the various mechanisms, so there's
Speaker 2: a lot more detail there if you want to know
Speaker 2: all about it. One of my favorites for just a
Speaker 2: very good overview was a paper from twenty twenty in
Speaker 2: Frontiers in Pharmacology titled the Analgesic effect of Acida menifin
Speaker 2: a review of known and novel mechanis of action. I
Speaker 2: thought that was a great overview, but there's a ton
Speaker 2: more and I will link to that pro Publica article
Speaker 2: if you want to dig deep on all of that business.
Speaker 2: So we'll post all of our sources from this episode
Speaker 2: and all of our previous episodes and future episodes on
Speaker 2: our website, This podcast will Kill You dot Com.
Speaker 1: We certainly will thank you to Bloodmobile for providing the
Speaker 1: music for this episode and all of our episodes.
Speaker 2: Thank you to Leana Squilacchi for the amazing audio mixing.
Speaker 3: And thank you to exactly right, and thank.
Speaker 2: You to you listeners. Hopefully you enjoyed this episode, you
Speaker 2: learned something, it was interesting.
Speaker 1: Yeah, And a special thank you as always to our
Speaker 1: wonderful generous patrons. Seriously, thank you, thank you, thank you.
Speaker 2: We can't we can't do it enough. It's true thanking.
Speaker 3: It's to you.
Speaker 1: Well, until next time, wash your hands.
Speaker 2: You filed the animals ob ob
Speaker 1: Oba oh