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Science Attacks The Mystery Of Tylenol 42

nm1m writes "For decades, millions of physicians have advised their patients to take acetaminophen - the drug behind "aspirin-free" pain relievers like Tylenol - without understanding how or why the popular medicine works. Now, a professor at Brigham Young University has discovered what could be the enzyme the drug attacks to relieve pain."
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Science Attacks The Mystery Of Tylenol

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  • That they didn't really know what this drug was doing... mind you I guess that's what most drugs do.

    It just kind of underlines how little we know about the human body and the chemicals that operate it.
    • A friend used to say:

      Doctors who know little put chemicals about which they know less into our bodies about which they know nothing at all.

      Oh, BTW, he's a vet.... I have much respect for someone who can succesfully treat patients who have all sorts of different physiologies, can't talk to tell what's bothering them, but instead aren't shy to use their teeth, beaks, horns and claws.

      • I have much respect for someone who can succesfully treat patients who have all sorts of different physiologies, can't talk to tell what's bothering them, but instead aren't shy to use their teeth, beaks, horns and claws.

        A vet goes to their doc, and gets impatient with all the questions.

        "What is it with you MDs? What is with all the questions? I don't have to ask my patients a bunch of questions! Am I a better diagnostician than you are?

        "OK" says the doc. "We'll try it your way." So the MD does all the physical stuff. Temperature, blood pressure, reflexes, and so on.

        Then they write out a prescription. "I want you to talk two of these a day, for ten days."

        "But I'm afraid, if that doesn't work, we'll have to have you put down ."

    • Hell yeah it's scary. Drug companies don't know shit about the drugs their dispensing.
      Those zoloft [zoloft.com] commercials really get me
      Although the way Zoloft works for depression, panic disorder, OCD, and PTSD is not completely understood, what is understood is that Zoloft is a medicine that helps correct the chemical imbalance of serotonin in the brain.
      translation "We don't know what the fuck this drug really does, but buy it so we can make lots of money. Also try to get the government to pay for it, especially for old people. Everybody over 50 is entitled to all the money you will ever make, you aren't worth shit!!
      oops a little off topic there...
      anyway, they don't know what drugs do, they just know that for some people they sometimes fix this, but they also cause hair loss, constipation, nausea, sudden death, whatever "side affect" your favorite drug maker downplays.

      In closing, don't do drug...Just say NO!
  • I had always thought that headaches were caused by tension in the muscles around the skull. I had also assumed that Tylenol relieved the pain by relaxing those muscles or helping to dissipate the stress. I guess it was something my mom had said when she was in nursing school. It is interesting how little we understand about ourselves. I wonder what other drugs are out there that are frequently prescribed, and about which doctors either don't understand how they work or don't fully understand the effects.
    • Well considering a lot of the drugs that fall under the 'controlled substance' category used to be recommended by doctors, I'm guessing a lot.
      Cocaine was a cure-all up until the late 1800s, PCP and ketamine were used as anaesthetics until the 60s/70s.
      Morphine is still widely prescribed, and I'm pretty sure the doctors don't know too much about it except that its really addictive and it really works (until you develop a tolerance, as is the case with any drug).
      Hell, even ritalyn is still widely used, and considering it affects everyone differently (could be an upper, could be a downer, who knows until you try it right?)
      I'm guessing many of the original drugs currently on the North American market are only there today because of something akin to a 'grandfather clause'.
      I'm sure if it had gone through the 'rigorous' testing todays pharmaceutical companies had to go through to get a drug past the FDA, it would not have made it.

      Bear in mind I am not a pharmaceutical chemist and this post did not come out of any textbooks, instead from various sources (some you may feel are questionable) like Discovery channel and my own research into some of the things I have taken over the years. If I'm wrong, correct me so I don't make the same mistake again.
      • Those are some interesting ideas.

        Regarding morphine in particular, I have read in a couple of places that the more pain a patient is in, the more of morphine and other pain relievers they can tolerate. For example, a patient in late stages of cancer can tolerate doses of morphine that would kill a healthy person.

        I apologize but I do not recall the sources for this information.

        • this mostly has to do with tolerance...

          the mu (as well as the other opiate receptors such as kappa, delta, etc-although these aren't necessarily analgesic) receptors show a huge degree of tolerance to extended dosage duration, people with end-stage cancer usually have been on opiates for a very long time and thus it's not uncommon for some patients to be using 1000mg + per day of morphine, whereas the normal dosage (lets say if you came into an ER after an auto accident) would generally only be 2-4 mg every 4 or so hours... if you're pushing the morphine dose for several months regardless of your pain level, i promise your tolerance will increase dramatically as well...

          -tid242

      • by sessamoid ( 165542 ) on Wednesday September 18, 2002 @12:22AM (#4279364)
        PCP and ketamine were used as anaesthetics until the 60s/70s.
        Actually, ketamine is still used occasionally as an anesthetic and for procedural sedations, particularly in children who have fewer side-effects from it. I wasn't in practice in the 60's and 70's, but I don't recall ever hearing about PCP being used as an anesthetic, and it's a doubtful thing considering it has no real value as an anesthetic that I can think of. My experience with PCP is thankfully limited, however.
        Morphine is still widely prescribed, and I'm pretty sure the doctors don't know too much about it
        Actually the action of morphine on mu opiate receptors in the brain is fairly-well (though not completely) understood.
        If I'm wrong, correct me so I don't make the same mistake again.
        Request granted. ;)
        • but I don't recall ever hearing about PCP being used as an anesthetic

          PCP was actually origionally tried for anesthesia but due to the adverse effects of the drug after surgery was quckly written off for this purpose... FYI ketamine is still widely used in the vet. industry as it's 'safer' than traditional anesthetics in terms of respiratory depression and the like, a farmer can walk into a pasture with a syring full of ketamine, stab the cow with it, perform whatever on the cow, and walk away, the cow eventually wakes up... at least that's what one of my old Neuro profs had said once...

          i concur with your morphine statement...

          -tid242

    • I see a lot of people treating acetaminophen and ibuprofen as the same in the comments. I'm no doctor, but just in my personal experience, I find ibuprofen vastly more effective for me. I believe that acetaminophen (Tylenol) is a pain blocker, where ibuprofen is more an anti-inflammatory. Since a lot of my headaches and other pains have to do with lack of sleep, tense nerves and sinus infection (I'm a student, work full time and have pretty harsh seasonal allergies), ibuprofen works wonders. I can feel the nerves relaxing after I take the stuff. Tylenol doesn't do much for me, though I hear it is more effective as an actual pain blocker. Of course, like I said before, IANAD.
    • Your opinion is nice, but only applicable to the headaches which you've encountered which seemed to respond as you expected -- whether the behavior was truly what you believed or not.

      Some headaches are indeed "tension" headaches where relaxing the affected muscles can help, whether done with meds, distraction, or conscious relaxation of the individual muscles.

      Some headaches are not related to muscle action. If inflammation is involved, it's better to treat that than only blocking the pain. If heat/fever is a cause, then tinkering with the body's thermostat can help, meds can help alter circulation behavior, or direct chilling may be needed (cold drinks, sweat cooling, cool shower, ice pack, body ice pack, abdominal lavage, blood chilling...). Or there are messier possible reasons, such as pain due to physical damage to skin or muscle in the head area (by "physical" I mean damaged tissue for any reason, not only bodily impact, as pain is primarily supposed to report damage).

  • The press release says this is how they identified the enzyme:

    1. We know that NSAIDs (non-steroidal anti-inflammatories) like Aspirin or Ibuprofen block COX-1 and COX-2 enzymes.

    2. We know that COX-1 enzymes help protect the stomach while COX-2 enzymes cause pain sensations and inflammation.

    3. We looked at monkey brains and saw that there was an enzyme we know nothing about. It happens to show up in human hearts and brains too.

    4. We saw that acetominophen (tylenol) blocks it.

    Therefore the way that tylenol works is that it blocks this one enzyme. Since it seems related to pain let's call it COX-3

    Sounds like another case of someone saying that correlation=causation. Did they check if tylenol affects the other 8 zillion chemicals in the body?

    • I believe if the explanation you have provided is correct, they will be starting on body chemical number four sometime early next week. :)
    • Therefore the way that tylenol works is that it blocks this one enzyme. Since it seems related to pain let's call it COX-3
      It's not nearly as simplistic as you assume. The cyclooxygenase enzymes are very well defined. We know them down to the atom. The myriad actions aren't necesarily understood in all parts of the body, but the mechanism by which they're involved in pain response is fairly well-understood. These researchers did not just pick "COX3" as the name out of blind stupidity. I'm assuming that the cyclooxygenase-3 is chemically very similar in both structure and function to the other two. There are at least hundreds and thousands of other enzymes related to pain response, but we don't name them COX just because they're related to pain.
    • What the press release is skimming over is the fact that COX-2 and COX-3 are very similar. It was originally discovered as a *variant* of COX-2 that specifically responded to the same inhibitor (which are used in biochemistry as a marker for a particular enzyme) but had slightly different chemical properties (it binds acetominophen as well). See this paper [pnas.org] from the same lab in 1999. So the logic is more like this:

      1. We know that NSAIDs block COX-1 and COX-2, and this blockage is responsible for their analgesic activies.

      2. Acetominophen blocks a variant of COX-2 (called COX-3) in much the same way that other NSAIDs block that class of enzymes.

      3. Since COX-2 and COX-3 are chemically similar (possibly variants of the same gene), we presume they have similar functions.

      Therefore, acetominophen acts as an analgesic because it blocks COX-3. It's not absolute proof (and undoubtedly they shall research it further!) but it is in fact very likely. In any case, this most recent study is only saying that COX-3 is found in human hearts and brains-- they're mainly trying to prove that the variant they discovered previously is actually found in vivo.

    • >The press release says this is how they identified the enzyme

      There's the problem right there-- you are relying on a press release for scientific information. I'm glad to see that you are using analyzing what you read, but GIGO...

  • How Caffeine works... [utexas.edu]
    How Beer works... [howstuffworks.com]
    How Pot works... [ndsn.org]

    Google is great for finding out important, health-related information. :-)
    • Aww jeez, not that "pot does the same as heroin" thing again! Sigh.
      Lets see, heroin users become physically dependant and quite often die of an overdose. Pot heads can quit in a snap (they'll be grumpy for a week or so, but they won't scream in pain or go nuts) and it has never killed anyone ever in thousands of years of recorded use.
      Like the article says, this study proves that pot is as similar to heroin as chocolate. I really don't see any non-propaganda point to these studies.

      That cafein article is really interesting though...
      Caffeine has some negatives and positives, that much is certain.

      Yup! Perks you up in the morning, makes you insomniac at nigh! : )
      • Ya, pot just makes you stupid after a while. I know it's only anecdotal, but all of my friends who somewhat regulary smoke pot respond slower to dialog. There is also reasonable amount of science backing this up of you google for it. Sure, I don't buy the Pot==Heroin bit, but I'm still not convinced that it's a safe enough substance for public trade and consumption.
        • I know it's only anecdotal, but all of my friends who somewhat regulary smoke pot respond slower to dialog.

          They need some cafein to balance it out : )

          I don't buy the Pot==Heroin bit, but I'm still not convinced that it's a safe enough substance for public trade and consumption.

          You're right, it isn't 100% safe...I know, lets put people who smoke it in jail! Jail is good for you...having human feces thrown at you fortifies your immune system!

          I don't see why warning labels shouldn't be enough.

          Now, the people who deal in MSG, THEY should go to jail...scratch that, they should fry.
          • You make some good points, but I never asserted that it was "a little unsafe" like Red Bull for example. I'm saying that it may be much more dangerous then a lot of us would like to believe. Jail has nothing to do with what's best for the criminal, it has to do with punishment for a crime. If we believe that the trafficking of a substance is dangerous, we want to deter that crime with a serious punishment. If pot is not this substance, then ya, it's kind of rediculous and we should change the laws. I just personally haven't made up my mind yet.
            • I'm saying that it may be much more dangerous then a lot of us would like to believe.

              Yeah, I mean, look at all the babyboomers...they are all braindead by now eh? All the ex hippies all got so brain damaged they became mentally ill and went homicidal and ... oh, no, that's right, they didn't. They became normal middle class drones...damn.

              Jail has nothing to do with what's best for the criminal, it has to do with punishment for a crime.

              Indeed. I'm saying: Pot smoking should not be a crime. The goal of criminalisation was to protect the public from becoming hopelessly addicted and incurably insane from that evil devil's weed. It was stupid and that mistake should be rectified. They stopped alcohol prohibition when they realised it was a lost cause. but for some reason they keep on with the pot laws as if they were a god-given holy law.

              If we believe that the trafficking of a substance is dangerous, we want to deter that crime with a serious punishment.

              Indeed. That is why I want the Monosodium Glutamate producers/dealers to get death sentences. Its addictive, it makes people sick, and it causes brain damage in rats (when injected in large doses).

              But that doesn't justify the jail sentences for simple possesion. If the dealing is the crime, why is the buyer's life destroyed? (The pot doesn't destroy the pot head's life, the cops do.)
              I know a few regular pot smokers (and a bunch of party pot smokers), I don't want their lives destroyed. I don't want them thrown in jail. They can smoke tobacco and drink beer all they want, but a joint could make the police destroy their life. That's not right!

              If pot is not this substance, then ya, it's kind of rediculous and we should change the laws. I just personally haven't made up my mind yet.


              I propose a very unscientific and dubious experiement: Go rent a heroin movie (Trainspotting or Requiem for a dream [imdb.com]) and then a pot movie (Half Baked...can't think of another good one right now), and see if they deserve to be in the same category.

              Here's a link [hhs.gov] that supports your "its bad for you" line of thought.
              Here's what I think about it: DUH! Well, if you're smoking pot every day for years and you suddently stop and take a test, of COURSE you'll do bad! And of course students and yungins shouldn't smoke pot! These things (pot, booze, cigarettes) should only be used by grownups, and only when apropriate.
              But when you're old enough to vote and go get killed to protect your country. You're also old enough to make your own choices about drinking or eating or smoking what you want. If the governments don't want you too, they should educate you (without lies) and give you resources to help you get back on their idea of the right track. Not destroy you if you use your free will to do things they don't agree to.

              Hey, I wouldn't even mind if they kept the dealing laws, because it is possible (if rare) to be addicted to pot, and so anyone who's dealing in it has an incentive to encourage abuse and addiction, but responsible users don't need to be marginalised for their choices.

  • by ChadN ( 21033 ) on Wednesday September 18, 2002 @01:39AM (#4279598)
    A recent issue of "Science News" magazine (within the past two months), had an article about an experiment where Guam's brown snakes were fed rats stuffed with about 6 acetaminophen (the active ingredient in Tylenol) tablets. All the snakes that ate the rats later died, even the ones that regurgitated them fairly quickly after swallowing them.

    Since the brown snake is an introduced pest, and is highly dangerous to the bird population, this discovery is seen as a way to poison the snakes, with hopefully minor side effects for other animals.

    And if I were a lawyer, I'd stick to Ibuprofin (ba-dum-bum)
    • APAP (Acetaminophen) has long been known to be hepatotoxic, which is why it's generally stated to not take more than 3 grams (reg = 325mg, ES = 500mg, and arthritis = 650mg) per day chronically, or 4 grams per day acutely (less than a week or two), and AFAIK tylenol poisoning far outweighs all of the other poisonings in the US every year. one of the metabolites of APAP causes hepatic necrosis (liver damage), which could plausibly be its detriment to the snakes, especially if they're given 6 tablets, that's 2 grams at a minimum, compare the average 70kg person (unless you're in American, then you can tack on another 10-15kg) to the weight of the average brown snake, probalby not more than a couple of kg's. this is of course assuming that the drug is metabolised the same between the two species, which i don't know..

      -tid242

      • How does APAP compare to ibuprofen from the toxicity perspective? I know ibuprofen is also not good for the liver, but is it similar/better/worse than APAP?
    • You have to read the article more carefully.

      Apparently it was only fatal to snakes without headaches. To snakes which had headaches at the time, it made them feel clear and refreshed, ready to take on the world.

      They also fed some snakes equinox, and those ones stopped worrying about the deaths of their brethren.

      Just goes to show - Drugs are good.
    • The hard part was training the rats to eat the acetamitophen tablets.
  • I have been told that Tylenol also contains caffiene, apart from the main active ingredient mentioned in the article, which combats the symptoms of caffiene withdrawal (usually in the form of a headache).

    Can anyone confirm this? (Google was not its usual helpful self)
    • "Tylenol" is a brand name, so there is "Tylenol PM" which contains diphenhydramine (Benedryl) and probably other "Tylenol" variations, i am unsure if one of them contains caffeine however. this article is talking about APAP (acetaminophen), the active ingredient in traditional "Tylenol" not whatever name-brand product iterations you might find at whitetrashmart, er... i mean: Wal-mart.

      you may be thinking of Excedrin, which generally contains APAP, ASA (aspirin) and Caffiene...

      }8^)-~

      -tid242

    • I have been told that Tylenol also contains caffiene, apart from the main active ingredient mentioned in the article, which combats the symptoms of caffiene withdrawal (usually in the form of a headache).
      Tylenol is straight acetaminophen. Anacin is aspirin and caffeine. Some people say caffeine enhances the analgesic effect of aspirin, and aspirin and cola have long been a popular combination.

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