The pain is killing me

November 27, 2011 11:19 AM

Even a little too much Tylenol over a few days can cause a liver failure. Paracetamol or acetaminophen, active ingredient of such over-the-counter painkillers as Tylenol, Panadol, Anacin-3 and many, many others, is considered safe - and it is, in prescribed doses. But even a single overdose can lead to liver failure despite treatment, and then only a liver transplant can avert a fatal outcome.

In light of this, according to the recommendations of the FDA some manufacturers are reducing the dosage, as discussed previously.
But now a study (abstract, pdf) published in British Journal of Clinical Pharmacology has found a higher mortality (37%) among patients with so called "staggered overdose" of paracetamol (on average 24 grams over three days) than among those who took one huge dose (28% mortality, on average 27 grams, or 54 Extra Strength Tylenols, 500 mg each).
To ingest 24 grams in three days one still has to overdose heavily (16 extra strength pills per day, 10 over the limit), but "staggered overdose" cases are defined as having ingested 4 or more grams (8 or more pills) in the course of three or more days.
So, if you feel safe because who's so crazy to take 50 Tylenols, consider an example - you have a really bad back, you pop just two extra strength pills over the limit and the pain goes away, only to return the next morning. If you repeat the pattern for the next two days, you risk liver failure - and for at least one of the patients in the above study such seemingly small overdose proved fatal.

posted by hat_eater (108 comments total)

Worse is that they put this stuff in prescription painkillers, not to reduce pain, but to discourage overdosing by killing the patient. I don't even know why they sell this stuff.
posted by Blazecock Pileon at 11:29 AM on November 27, 2011 [42 favorites]

anything with acetaminophen doesn't work for me and just gives me pain instead.
I go with ibuprofen instead.
posted by sweetkid at 11:38 AM on November 27, 2011 [3 favorites]

I'm confused by some of these numbers -- a staggered overdose can be achieved by "8 or more pills over 3 days"? This means 8 pills/day or 8 over 3? And even though this is the case, the typical staggered overdose is 16 pills/day?
posted by modernnomad at 11:38 AM on November 27, 2011 [2 favorites]

Worse is that they put this stuff in prescription painkillers, not to reduce pain, but to discourage overdosing by killing the patient. I don't even know why they sell this stuff.

Acetaminophen is a very important pain medication for people with GI complications (e.g. ulcerative colitis, Crohn's disease). Since NSAIDs are contraindicated, and opiates would be inappropriate for low grade pain, acetaminophen is basically the only reasonable choice, not only for the pain associated with their condition but also for ordinary aches and fevers.

The issues with acetaminophen should be solved with patient education and packaging changes, not denying people access to useful medication that is extremely safe when taken appropriately.

consider an example - you have a really bad back, you pop just two extra strength pills over the limit and the pain goes away, only to return the next morning

Acetaminophen does not become more effective past the maximum dose, so taking extra pills would not help. This is another example where patient education is important.
posted by jedicus at 11:39 AM on November 27, 2011 [40 favorites]

Acetaminophen does not become more effective past the maximum dose, so taking extra pills would not help.

How did I live my life this long without knowing this?
posted by LooseFilter at 11:43 AM on November 27, 2011 [11 favorites]

(not that I tend to just throw extra pills at problems, but still...seems like that should be printed in bold on the box: EXTRA PILLS WILL NOT HELP YOU AND MAY VERY WELL KILL YOU)
posted by LooseFilter at 11:44 AM on November 27, 2011 [21 favorites]

I have been taking Acetaminophen PM for about 20 years. This scares me.
posted by UseyurBrain at 11:49 AM on November 27, 2011 [1 favorite]

It would pay to read the abstract instead of the linked Discover magazine article which is unnecessarily alarming.

The abstract states:
Between 1992 and 2008, 663 patients were admitted with paracetamol-induced severe liver injury, of whom 161 (24.3%) had taken a staggered overdose

So in a 16 year period in the UK, a period where likely at least 16 million people took acetaminophen (assuming a conservative 1.0 million doses a year), 663 suffered a serious injury . That is a percentage of risk of .004% per dose which is pretty low.

But wait there's more.... the abstract goes on to to say

Staggered overdose patients were significantly older and more likely to abuse alcohol than single time point overdose patients.

So the 663 people studied over a 16 year period were older (i.e. more likely to have existing liver problems) and abused alcohol more than the general population. So you likely need those additional risk factors before the .004% risk factor comes into play.

Which is a darn sight less scary than saying that even a single dose of Tylenol can destroy your liver.
posted by Poet_Lariat at 11:49 AM on November 27, 2011 [38 favorites]

Painkillers are for wimps, anyway.
posted by Decani at 11:53 AM on November 27, 2011 [1 favorite]

When you grow up with someone who can't take aspirin, you learn about the nasty effects of Tylenol pretty quickly. Fun story, he had a headache in Amsterdam and asked the clerk for some Tylenol, the clerk got this very spooked look on his face and said, calmly and softly "it is forbidden in our country" so, I took him a few blocks down to have his very first spacefood cookie. Cleared the ache right up.
posted by The Whelk at 11:55 AM on November 27, 2011 [28 favorites]

Acetaminophen does not become more effective past the maximum dose, so taking extra pills would not help.

True, but taking Norcos/Vicodins - which are combo pills of 325mg acetaminophen and 5mg hydrocodone (1-2 tabs taken q4-6hrs) - past the max prescribed dose is a gift that keeps giving. I wonder how many of the OD's are due to the "hidden" tylenol in these pills.
posted by klarck at 12:00 PM on November 27, 2011 [11 favorites]

Painkillers are for wimps, anyway.

Speaking as someone prone to gout, you're wrong. If you want to replicate the experience have someone insert a crowbar between the ball of the big toe and the foot and try and separate them every fifteen minutes or so for several days. Under such circumstances I've consider amputation and heroin in roughly that order.
posted by Grangousier at 12:02 PM on November 27, 2011 [7 favorites]

In more than one of my pharmacological lectures, both with clinicians and with pharmacologists and pharmacists, it has been stated that if acetaminophen had to be evaluated by current FDA OTC standards, it wouldn't make the cut--not that it doesn't have effective applications, but that it may not be an appropriate OTC medication because it's therapeutic range is so narrow (difference between toxic and therapeutic dose).

OTC analgesic literacy, in general, is poor. Many patients report taking "aspirin" when they may have taken (or in my case, given to a child, b/c I work in pediatrics) ibuprofen, aspirin, naproxen, or acetaminophen (sort of how some parts of the South call a lot of different kinds of soda "coke"). Dosage range understanding is poor, often due to the labels themselves who equate the direction "day" with "24 hour period" (which is correct--a pharmaceutical day is 24 hours) even though most patients interpret "day" as "waking 12 hour period." Many don't understand the difference between NSAIDs and pain relievers, and which to take for different therapeutic outcomes. More, many OTC polydrugs (combination serums, syrups, and tablets--often for cold/flu symptoms) incorporate analgesics and so patients may overdose when they take these in addition to pain-relieving tablets. Sleep aid analgesics and Rx acetaminophen+opioid preparations are notorious for feeding patients a steady stream of acetaminophen they don't need.

Children under 6 months can't use ibuprofen due to kidney immaturity, and no child can take aspirin in any case because of Reye's syndrome (except under a provider's DIRECT supervision for certain vascularly-mediated childhood diseases), so for pain, acetaminophen remains the safest OTC choice for infants. Infant drops, in which the solution was formulated so differently from children's acetaminophen, were removed from shelves because of caregiver dosing error--the same reason why combination OTCs have been severely restricted for children. Many pediatric providers have found that it is incredibly important to give new parents dosing charts because acetaminophen is an extremely common poisoning agent for infants and children. Further, acetaminophen's taste is easy to disguise in sweetened syrups, so kids OD themselves.

It is true that this concern, at least for adults, cycles through the literature every few years with varying degrees of alarm. At the very least, it's a reminder to ask your provider about the differences and dosages for analgesics and figure out with them good choices for yourself when you have pain or inflammation. And a reminder to be honest with your provider about alcohol and tobacco use--which changes harm and action of these OTCs.

Just when I think most of us have kind of got it, I'll hang out with my mother-in-law and be reminded all over again that people still haven't internalized the message that just because it's OTC doesn't mean it's "safe" or "more gentle" (somehow. Jeez, Woman). So educate your older friends and family, too (I totally check out the OTCs and Rxs in my older relatives/friends cabinet--with their permission--and go through it for safety/education. I find it relaxing).
posted by rumposinc at 12:04 PM on November 27, 2011 [61 favorites]

Acetaminophen is a very important pain medication for people with GI complications

What I was talking about is the use of acetaminophen specifically as an adulterant to prescription painkillers, where it serves no medical purpose. It is put in painkillers specifically to sicken and kill people who take too many — that is pretty much the only reason for its addition; not a situation much different from the government adding methanol to ethanol during Prohibition.
posted by Blazecock Pileon at 12:05 PM on November 27, 2011 [12 favorites]

I have been taking Acetaminophen PM for about 20 years. This scares me.

Do you take it in order to sleep? Because you can buy the sleep ingredient of the pill without the pain reliever part.
posted by MaryDellamorte at 12:05 PM on November 27, 2011 [3 favorites]

It 's worth noting that acetaminophen overdoes in the U.K. are mostly intentional whereas accidental overdose is more common in the U.S. due to the med's ubiquity in combination painkillers and its higher dosage per pill. Between four extra strength Tylenol and two standard migraine pills, there's enough acetaminophen to bring you above the 2.7 gram daily maximum.
posted by The White Hat at 12:06 PM on November 27, 2011 [1 favorite]

BP, there is evidence for a synergistic effect between the opioids and acetaminophen that improves analgesic effect. At least that's the party line on the reason for their combination in vicodins et al.
posted by klarck at 12:11 PM on November 27, 2011 [1 favorite]

This is a pretty scary post. My Dad has been taking a lot of doctor prescribed Tylenol for years, and his liver isn't the greatest. (From age, not alcoholism.) But they must be small pills, because I just did the math and it adds up to 2.6 grams a day. His doctor is keeping him just below the maximum dose. Anyway, now we know not to ever take extra! Thanks for the frightening but informative information, hat_eater.
posted by Kevin Street at 12:14 PM on November 27, 2011 [1 favorite]

"Acetaminophen is a very important pain medication for people with GI complications (e.g. ulcerative colitis, Crohn's disease). Since NSAIDs are contraindicated, and opiates would be inappropriate for low grade pain, acetaminophen is basically the only reasonable choice, not only for the pain associated with their condition but also for ordinary aches and fevers."

This is entirely avoiding his point and is misleading in its implication that it refutes it.

I'm prescribed a high dose of a strong NSAID. I also am prescribed a pretty strong opioid. But the opioid medication contains a lot of acetaminophen that I don't need and unnecessarily loads my liver when it's already being pushed by other meds I'm taking.

And the only reason for this is because of exactly what BP asserted: the acetaminophen is included so the med can't be injected and will cause overdoses if the opioid is badly abused orally. Sure, it's therapeutic for many patients. That's not the issue. The issue is that it's essentially impossible to get opiates/opioids without either an NSAID or acetaminophen included unless you're a cancer patient or hospitalized for precisely this reason, regardless of how many people die each year from acetaminophen overdoses as a result.

I'd wager money that the number of people who die from an acetaminophen overdose from its inclusion in opiate/opioid medications is very close to (or greater than) the number who die from an opiate/opioid overdose from the same medications. Particularly because, as is discussed here, acetaminophen is included in a large number of OTC medications, as well, and people aren't aware of this.

It's a stupid, deadly consequence of the US's hysterical anti-drug culture.

"BP, there is evidence for a synergistic effect between the opioids and acetaminophen that improves analgesic effect. At least that's the party line on the reason for their combination in vicodins et al."

Again, it's not that the combination isn't clinically useful for many patients. What's revealing is that it's extremely difficult to get an opiate without an NSAID or acetaminophen even when it's not indicated for a particular patient. And that this isn't the case worldwide, just especially in the US.
posted by Ivan Fyodorovich at 12:20 PM on November 27, 2011 [25 favorites]

the clerk got this very spooked look on his face and said, calmly and softly "it is forbidden in our country"

A few minutes of searching only turns up this 2010 Radio Netherlands Worldwide story in which the Dutch Society to Promote Pharmacy "wants sales limited to packets of 20". There's no indication in this story of there ever being a ban in the Netherlands, or of anyone calling for one.

Is it possible the clerk misunderstood?
posted by stebulus at 12:20 PM on November 27, 2011

quite possibly.

Sigh facts ruin great anecdotes.
posted by The Whelk at 12:22 PM on November 27, 2011 [5 favorites]

I drown puppies too.
posted by stebulus at 12:23 PM on November 27, 2011 [1 favorite]

Not really.
posted by stebulus at 12:24 PM on November 27, 2011 [1 favorite]

If a patient would benefit from a combo drug then they can get two prescriptions instead of one. I have to specifically request standalone pain drugs or else I get the evil acetominophen laced evil kind. Other than paternalistic punishment there is no justification for including acetominophen with other drugs.
posted by yesster at 12:25 PM on November 27, 2011 [5 favorites]

I wish the "medical establishment" in the USA wasn't so paranoid of opiate-based painkillers. Maybe then they would treat chronic pain patients like human beings and not junkies.
posted by Val_E_Yum at 12:26 PM on November 27, 2011 [13 favorites]

True, but taking Norcos/Vicodins - which are combo pills of 325mg acetaminophen and 5mg hydrocodone (1-2 tabs taken q4-6hrs) - past the max prescribed dose is a gift that keeps giving. I wonder how many of the OD's are due to the "hidden" tylenol in these pills.

Vicodin is part acetaminophen?

How does House still have a functioning liver?
posted by Talez at 12:38 PM on November 27, 2011 [6 favorites]

How does House still have a functioning liver?

Better question is how does he still have a TV show?
posted by sbutler at 12:43 PM on November 27, 2011 [6 favorites]

Maybe he takes a lot of milk thistle extract during the commercials.
posted by Kevin Street at 12:45 PM on November 27, 2011 [1 favorite]

Well I assumed that Vicodin is a straight opioid because of how everyone in popular culture treats it like it's some sort of heroin variant.

You guys really get your panties in a twist with acetaminophen/opioid hybrids?

Australia must be a country full of junkies by US standards with 15mg codeine/500mg acetaminophen variants available over the counter.
posted by Talez at 12:49 PM on November 27, 2011

"Maybe then they would treat chronic pain patients like human beings and not junkies."

Don't even get me started. I've stopped taking opiates again just a few weeks ago because I'm just so damn sick of the whole deal. My current PCP won't prescribe them at all, and because the practice eliminated the pain specialist they had, I was going to need to find a new specialist to prescribe it anyway. But my longer-standing problem is that this practice's (and pretty much everyone's, these days, thanks for the DEA prosecuting doctors) paranoia about prescribing opiates meant that every month I had to call and request a renewal of my scrip...and I couldn't request it before the 27th day, or so. Because it took them a couple of days to get around to it, and because the pharmacy also took some time, and because people make mistakes, about one month in three I'd end up going into withdrawal because my scrip wasn't ready in time. (This is because I've been taking oxycodone for several years now and it has a short half-life—I start feeling withdrawal within 12 hours of the last dose and by 24 hours I'm in the full throes of it. The one-month-in-three thing also has a lot to do with whether someone makes a mistake or is slow to getting around to it and its a weekend coming up.)

And then family and friends have asked me, when this sort of thing happens, why I don't raise hell with the doctor's office. And the answer to that? Because providers are sensitive to what they perceive to be "drug seeking behavior", which signifies addicts. Well, yeah, when my prescription isn't filled in time and I'm going into withdrawal because I'm physically dependent (as distinct from addicted), then of course I'm "drug seeking". But having read a number of physician's blogs and physician's comments on this issue, I'm acutely aware of how paranoid many/most physicians are these days about opiates. Probably a majority of newly minted primary care physicians refuse to prescribe opiates at all, or at least regularly, out of fear of running afoul of the DEA and losing their license, at minimum and prosecution and prison, at maximum.

All the red tape and paranoia exactly makes even someone like me—who is obviously, visibly, in chronic pain, disabled, and justifiably prescribed opiates—feel like I'm being suspected of being an addict and a criminal. And, you know? All this taken together has resulted in me just not taking the medication I obviously need, as is the case now. I'm less functional, I can't leave the house as much, I can't sleep. But, hey...at least I don't have to worry every goddam month about getting my prescription refilled. There's that.

"How does House still have a functioning liver?"

Like (I suspect) the experts here, I'm hesitant to say this...but the 2600mg daily maximum has a built-in cushion in it accounting for people who have some degree of liver impairment and/or other things. If you look more closely at the literature, you'll see that with non-drinking, otherwise healthy adults, it's about three times that amount before it's moderately probable to cause liver failure. My own personal evaluation is that (again, healthy non-drinking adults who don't have any liver impairment or other medication liver loading) is that in 24-hours, about 5000mg is worrisome, 8000mg is actually dangerous, and 11000mg is in the range where there's a good chance of death.

But, really, there's so many variables in this and so many people drink, and so many people take other drugs that load the liver, and so many people have undiagnosed impaired liver function, and so many people unknowingly take acetaminophen, that just considering 2600mg as the daily safe maximum is by far the wisest way to think about this.
posted by Ivan Fyodorovich at 12:50 PM on November 27, 2011 [24 favorites]

Aaaand this is why this particular aspirin-and-ibuprofen-sensitive lady just deals with headaches. I'd rather ruin my liver drinking wine if I'm going to ruin my liver, thank you much.
posted by troublesome at 12:51 PM on November 27, 2011 [2 favorites]

There's evidence that tylenol helps the effectiveness of opioids (small study; there's other evidence out there but this is the best that I could find quickly)

It would make sense to combine it in pills like percocet, as it is desirable to try to limit an individual's intake of opioids - as seen here there is a down side to their use.

Also, acording to the above they were taking on average 24 grams over three days, or 8 grams a day which is too much. 3 grams a day is the recommended limit.
posted by deliquescent at 12:51 PM on November 27, 2011

15mg codeine/500mg acetaminophen variants available over the counter.

Ahhhhh he might have been asking for this, compounded by being jetlagged and in pain.
posted by The Whelk at 12:52 PM on November 27, 2011

I hate acetometaphen. It is junk added to my scripts to be "synergistic", even though Europe and other countries have banned or nearly eliminated the process. I'd much rather take whatever opioid I'm scripted with out it. No need for it, and its usefulness has been questioned multiple times. Hell, even the DEA recommended the practice to prevent abuse. As if people who are abusing drugs generally care if its in there or not. Besides the ethical questions that arise from such an agency, punishing individuals taking drugs in combo with acetometophen is simply misguided and wrong.

Luckily, there is the cold water extraction technique to seperate opioids from acetometaphen which works particularly well.
posted by handbanana at 1:01 PM on November 27, 2011 [6 favorites]

Yeah, I won't take acetaminophen. I do cold water extractions if I have Vicodins or whatever prescribed to me for any reason.
posted by Justinian at 1:03 PM on November 27, 2011 [3 favorites]

Children under 6 months can't use ibuprofen due to kidney immaturity

I hadn't heard of this, and the couple of links that I just looked at don't mention this safety concern at all, in fact many of them explicitly state that ibuprofen is safe for infants.

Could you clarify your source for this?
posted by odinsdream at 1:04 PM on November 27, 2011

OK so apparently Tylenol with Codeine Elixir is 12mg/120mg per 5mL and is Schedule V and available from a pharmacist while 30/300 tablets are Schedule III and only available with prescription?

So I could walk into a pharmacist, grab a bottle of elixir and take 15mL of it but I need a doctor to prescribe a bloody Tylenol 3 pill?

What the bloody hell kind of pants on head retarded system is this?
posted by Talez at 1:09 PM on November 27, 2011 [1 favorite]

That USAToday article linked by deliquescent is bullshit propoganda. It intentionally conflates "abuse of prescription painkillers" with the risk of legitmate pain patients becoming addicts when, in fact, the two things are distinct (though related; and there's some overlap). Specifically, it completely elides the illegal trade in prescription opiates, including both addicts who initially seek opiates from physicans because they're addicts and phony patients who seek opiates from physicians to provide for the illegal trade in prescription opiates.

There are reams and reams of evidence proving that while the risk of pain patients abusing opiate medications and becoming addicts is somewhat higher than is the case for the general population; that number is still relatively very small and the likelihood of any given pain patient becoming an addict is less worrisome than, say, the likelihood they'll become addicted to alcohol.

More specifically, there are reams of evidence about the nature of addiction and it's just not the case that every person is equally likely to become an addict (to any given substance), subject to its availability. Alcohol is universally available to adults in the US, is self-evidently exceptionally prone to abuse and addiction, and yet it's not the case that even the majority of adults in the US are addicts. Just taking an opiate, even recreationally and not for pain, is certainly not a guarantee of addiction. For crying out loud, not even all regular heroin users become addicts and there's few things more powerfully addictive and positively reinforcing.

And for those of us with chronic pain—perhaps not all of us but most of us, I think—it's difficult if not impossible to get a "high" out of a prescription oral opiate anyway. I've never experienced anything like a "high". The closest thing to an opiate high I've ever experienced was one time when I had a kidney stone (I've had five; but only once did I find the morphine or fentanyl or whatever to be distinctly pleasurable). If you have pain, the opiate doesn't get you high. It just eases the pain. Obviously, that's dependent upon the severity of the pain. But then, most people with only slight pain aren't going to be taking opiates anyway.

This idea that pain patients who take opiates are at constant risk of turning into addicts is anti-drug propaganda that is completely contrary to decades of epidemiological data and research into the nature of substance abuse and addiction.
posted by Ivan Fyodorovich at 1:15 PM on November 27, 2011 [15 favorites]

I go with ibuprofen instead.
posted by sweetkid

You'd prefer a kidney transplant? Just spent the holiday with my brother who is a county ER supervisor in CA. For some reason the Hmong community out there is big on ibuprofen. But many people who come in with chronic pain, have already destroyed their kidneys with cumulative ibuprofen damage, to the point where he doesn't even talk to them about the prognosis, because it's basically palliative at that point.
posted by StickyCarpet at 1:30 PM on November 27, 2011 [1 favorite]

Ivan,
I was trying to reference the rise in mortality with opioid use: Between 1999 and 2002, the number of opioid analgesic poisonings on death certificates increased 91.2%, while heroin and cocaine poisonings increased 12.4% and 22.8%, respectively.

Specifically, I was trying to support the idea that adding acetaminophen to an opioid, in order to increase it's effectiveness as a painkiller, would be desirable as it could limit the total dose of opioids used. It may not work for every individual, but on a population wide scale it may be beneficial.
posted by deliquescent at 1:31 PM on November 27, 2011

odinsdream: here is the American Academy of Pediatrics dosing chart for ibuprofen, which you'll see starts at 6 months. My 2010, 17th edition of the Pediatric Dosage Handbook (the LexiComp bible for pediatric drugs), indicates that ibuprofen is only FDA approved for infants 6 months or older due to potential renal toxicity. The pediatric clinical guideline is 7.5mg/kg/dose every 6-8 hours starting at 6 months.

At this CDC link, scroll down to the topic on what OTC preparations to give children, and you'll see the 6 month guideline.

Some charts will give you weight guidelines (12-17 pounds for a starting weight), but I would caution parents against this. It's true that 12-17 is the average weight of a 6 month old, but some are larger at younger ages, and the issue is renal maturity since ibuprofen is excreted through the kidneys.

So it is safe for infants at proper dosages--as long as the infant is 6 months old (and adjusted for 6 months if a premature infant). Some practitioners may even cheat that age upwards if there is kidney concerns. While some clinical trials indicate relative safety in infants as young as 2 months, this was under very careful supervision, and you only see that kind of thing in hospitals, where monitoring is constant and there is clinical indication beyond pain.

I hope this helps. I chose the links for their longevity--I can't link to articles I find on PubMed because I'm a subscriber.
posted by rumposinc at 1:32 PM on November 27, 2011 [3 favorites]

And though I hesitate to link to a commercial site, even at Motrin's (most common OTC prep of ibuprofen) site, if you hover over the "infant motrin" selection, you'll see label indications for infants 6 months and older and the warning to "ask your doctor" for infants younger than 6 months. The reason is that there is no legal labeling for ibuprofen use in infants younger than 6 months. Because I wanted to replicate your quick search, I searched for terms ibuprofen and 6 months, and was easily able to get a glance at the clinical guidelines. And, like I said, Lexi-Comp editions the guidelines for practitioners and children's hospitals. If you want to learn more about adverse renal effects of ibuprofen use in infant patients, there are a lot of interesting studies coming out of looking at California and Minnesota's Hmong communities, who have significantly higher than average adverse ibuprofen events. Or memail for pdf links.
posted by rumposinc at 1:44 PM on November 27, 2011

"You'd prefer a kidney transplant? Just spent the holiday with my brother who is a county ER supervisor in CA. For some reason the Hmong community out there is big on ibuprofen. But many people who come in with chronic pain, have already destroyed their kidneys with cumulative ibuprofen damage, to the point where he doesn't even talk to them about the prognosis, because it's basically palliative at that point."

Not just kidney damage. There's a correlation between long-term, heavy use of iboprofen and pancreatic cancer. I think the evidence and research on this is thin, but provocative. I mention this only because I was reading numerous web sources on ibuprofen a few months ago for some reason—I don't know why, for some reason I spend a lot of my time researching things that just catch my interest—and I saw that bit of info. It jumped out at me because my father died from surgical complications (supposedly, apparently) from pancreatic surgery to remove a large cyst.

He'd been taking very large dosages of ibuprofen for literally decades. I inherited the rare genetic disease I have from him; it results in severe early-onset osteoarthritis and for most of his life the pharmaceutical treatment for the pain was limited and unsophisticated. Basically, he took prescription Motrin from the seventies through the nineties, at the least.

The NSAIDs are effective drugs, but they're so darn...indiscriminate. They inhibit both COX enzymes. That's good in that it reduces the inflammation related to tissue damage that causes pain. That's bad in that the inhibited prostaglandins (catalyzed by the COX enzymes) do a lot of important things in the body that you otherwise don't want inhibited, especially protecting the GI tract from its acid. It's like wielding (lightly) a sledgehammer to pound in a nail. It gets the job done, but other things are flattened as well.

The selective COX-2s are too new to make many definitive statements about; but personally I don't think the evidence about the others is any more encouraging than rofecoxib (Vioxx). They cause heart-attacks, I think.

And we here see the problems with acetaminophen.

That pretty much exhausts the effective and commonly available pain relievers other than opiates.

There's a huge need for better pain relievers at both the OTC level and safety as well as for more serious pain. Obviously, from what I've already written, I think that part of that need should be filled by increased use of opiates. But we really need better chemistry here. For that, we also need better biochemistry, obviously.

I know that there must be money going into R&D for new pain relievers. Well, I assume there is. But, on the other hand, given the ubiquity of aspirin, acetaminophen, and ibuprofen, their inexpensiveness, and their perceived (but not actual) safety—and stacked up against what happened in the case of Vioxx after the money was spent on it—you can see that maybe there isn't as much incentive to find better pain relievers as there ought to be.
posted by Ivan Fyodorovich at 2:02 PM on November 27, 2011 [8 favorites]

acetaminophen is basically the only reasonable choice, not only for the pain associated with their condition but also for ordinary aches and fevers.

Ha ha ha, Colitis sufferer here, and let me tell you using tylenol for colitis pain is like using a band-aid for amputation. Mind you, this hasn't stopped me from taking lots and lots of it as a younger, stupider, person. Mostly, I wish I had known about the ceiling effect, but I was so desperate for the codeine bundled up with it, I may have taken it anyway had I known.
posted by smoke at 2:08 PM on November 27, 2011 [1 favorite]

Vicodin is part acetaminophen?

There's also vicoprofen, which replaces the acetaminophen with ibuprofen, which is likewise said to have a synergistic effect with the opioid.
posted by homunculus at 2:16 PM on November 27, 2011 [1 favorite]

But, on the other hand, given the ubiquity of aspirin, acetaminophen, and ibuprofen, their inexpensiveness, and their perceived (but not actual) safety—and stacked up against what happened in the case of Vioxx after the money was spent on it—you can see that maybe there isn't as much incentive to find better pain relievers as there ought to be.

That's a depressing thought, but it makes a lot of sense.
posted by homunculus at 2:19 PM on November 27, 2011 [1 favorite]

It would make sense to combine it in pills like percocet, as it is desirable to try to limit an individual's intake of opioids - as seen here there is a down side to their use.

If you need to try to limit a hypothetical person's intake from afar, if you knew there was no way they could ever possibly need the dose that high, it might make sense to add an ingredient that could make them feel ill if they took too much. But this ingredient just kills them. That's hardly in their best interest. It's even worse if most people who take the drug don't know that it can do that. It's like the Doomsday device in Dr. Strangelove -- it's not a deterrent if nobody knows it exists.
posted by Adventurer at 2:20 PM on November 27, 2011 [5 favorites]

Interesting and disturbing. I've been taking ibuprofen for decades - since 1980 or so - for mild headaches. Initially I started with acetaminophen (tylenol) back in Sweden, and after trying it a couple of times, it just made me feel awful. Since then I've foresworn acetaminophen. But ibuprofen always worked great for me. Of course, I've been reading about the cardiovascular and gastric risks, but the pancreatic cancer risk is a new one for me. Ouch. I keep hoping that my pattern of use is not that extreme though - 800 mg every 3 days or so. So accept annoying headaches that get much, much worse without ibuprofen, or take ibuprofen which works great and eliminates the pain, and risk other health complications? Quality of life is important. I'm sticking with ibuprofen for now. I should keep closer tabs on the med literature though, in case something hideous transpires. What about the bennies though, Parkinson's and possibly maybe even Alzheimer's?
posted by VikingSword at 2:27 PM on November 27, 2011 [1 favorite]

Ivan, I'm sorry you've had to go through such trouble to have your pain properly addressed.

I got fed up with doctors ignoring my husband's pain, and I now go to Dr. Feelgood/Dr. Robert for his painkillers. Kind of a messed up society where drug dealers are more reliable than doctors!
posted by Val_E_Yum at 2:28 PM on November 27, 2011 [1 favorite]

Adventurer - I wasn't saying tylenol was helping to limit opioid intake because of the risk of liver toxicity (which is really just a dumb idea), I was arguing that it makes sense to combine tylenol and narcotics because they have a synergistic effect and can decrease the need for higher doses. Which would be a good thing.
posted by deliquescent at 2:29 PM on November 27, 2011

This worries me because a relative's non-English speaking live-in mother-in-law (charged with almost all the childcare), turned out to be dosing their newborn children with liquid Tylenol PM daily to keep them asleep and quiet. I have no idea how much they were dosed with or how long this went on (I heard about it after the fact, when they were about two years old) before the father found out and put a stop to it.
posted by Soliloquy at 2:31 PM on November 27, 2011

There's a correlation between long-term, heavy use of iboprofen and pancreatic cancer.

Right now I tend to go with either aspirin or naproxen sodium. Yeah, I might start bleeding into my GI tract. But at least my organs won't fail. I hope.
posted by Justinian at 2:44 PM on November 27, 2011

Wait - so the average overdose in this study is four grams per day? That is a massive, massive amount of Tylenol.
posted by koeselitz at 2:51 PM on November 27, 2011 [1 favorite]

Naproxen is in the same class of medications (NSAIDs) as ibuprofen, both can cause GI bleeding or kidney failure if you take too much. Not sure if the pancreatic cancer link mentioned above is drug specific or class specific. A list of NSAIDs are available here
posted by deliquescent at 2:54 PM on November 27, 2011

Wait - so the average overdose in this study is four grams per day? That is a massive, massive amount of Tylenol.

Well, in Australia, our equivalent product - Panadol - comes as 500mg pills, and recommended dosage is two pills at a time. So that's only 8 pills, or four dosages in a twenty-four hour period - quite doable. I've done it myself.
posted by smoke at 2:58 PM on November 27, 2011 [1 favorite]

Someone I know well recently returned from a trip with persistent shoulder pain. His doctor, a reputable MD, prescribed him Vicodin which he kept the guy on for three full weeks, with no improvement in the discomfort.

I asked him to describe the pain. "Sometimes it radiates down the arm, almost to the hand," he said. I asked him if he had told the MD that, and he assured me he had. I asked if the MD had suggested a chiropractor, since clearly the source of the pain was nerves and not muscle, given its radiant nature. No, he replied. "Has the doctor discussed what his next step will be?" "More painkillers" came the reply.

A friend and I finally convinced him to see a chiropractor, who used massage and stretching--no pills--to completely relieve the pain. Several days later he was still pain-free.

I'm disgusted with the amount of pills this MD was willing to throw at this guy, when clearly that was not helping. I'm even more disgusted with MDs who are unwilling to suggest drug-free alternatives.
posted by kinnakeet at 3:07 PM on November 27, 2011 [1 favorite]

I have been taking Acetaminophen PM for about 20 years. This scares me.

It shouldn't. This is an issue is one of acute poisoning, not chronic poisoning (like lead).

There is cyanide in lima beans, for example, but not enough to cause acute poisoning. Chronic cyanide poisoning isn't typically a thing (unless your diet is almost entirely composed of cassava.)

Even closer to home, if you ever find find yourself thinking, "I just don't know about enough horrible ways to die" look up the effect of eating an acute dose of sodium chloride. Fortunately, most people lack the force of will to eat a lethal does of salt.
posted by Kid Charlemagne at 3:08 PM on November 27, 2011 [1 favorite]

As a pharmaceutical company clinical research guy, most studies we've done or our competitors have done comparing our pain meds to acetaminophen has been at an acetaminophen dose of 4000 mg (i.e., 4 grams) /day. Obviously, these studies were approved by the FDA.

I'm not aware of any significant difference in adverse effects on liver function tests with either acetaminophen or comparators in these relatively long-term clinical studies.

Which is to say, 12 G (i.e., 4 G over 3 days) seems reasonable and appropriate (as opposed to nearly twice that reported in this paper). The big proviso is that these are studies in a very narrow group of patients, which excludes those with alcohol or liver problems. Indeed, the demographics of the patients in the study with alcoholic history is close to 50%. Also, although I only skimmed the article, I didn't see in the baseline demographic table a history of liver issues, either, which would be very informative.

Overall, though, if 4G/day isn't enough for patients' pain, then their docs need to brush up on their pain management treatment and consider alternatives. And frankly, acetaminophen kinda sucks as an anti-inflammatory analgesic compared to, say, naproxen or just about any other NSAID.
posted by ssmug at 3:11 PM on November 27, 2011 [1 favorite]

The selective COX-2s are too new to make many definitive statements about; but personally I don't think the evidence about the others is any more encouraging than rofecoxib

Curcumin/turmeric is a potent selective COX2 inhibitor with loads of clinical research that demonstrates its efficacy and no real side effects to speak of. But since it's a plant, most people disregard it. Perhaps it'll get some respect once Pfizer tweaks the molecule, patents it, and puts it in a $20 pill.
posted by gngstrMNKY at 3:21 PM on November 27, 2011 [2 favorites]

Sorry, deliquescent. I read that one badly.
posted by Adventurer at 3:22 PM on November 27, 2011

"And frankly, acetaminophen kinda sucks as an anti-inflammatory analgesic compared to, say, naproxen or just about any other NSAID."

Yeah, if the pain has a strong inflammatory component, then acetaminophen isn't the right drug for the job. That's why no one takes it for either form of arthritis. Unless they don't know better, anyway.

"Not sure if the pancreatic cancer link mentioned above is drug specific or class specific."

I just now tried to find where I saw that. I can't find it. I don't think I imagined it or got it wrong, because I was just now able to find some nebulous links between ibuprofen and pancreatitis in general. But, regardless, I do recall that what I saw was very, very thinly supported. It was more speculative in nature. Obviously, it caught my eye because of my father.

So, you know, I don't think that anyone should be worrying about this, really. Not compared to the well-known GI complications from ibuprofen and NSAIDs in general. Or renal impairment. Also, I think my dad was taking something like 5000mg+ a day for at least thirty years. That's a whole lot of ibuprofen.
posted by Ivan Fyodorovich at 3:25 PM on November 27, 2011 [1 favorite]

Regarding the pancreatic cancer risk, I found
posted by deliquescent at 3:33 PM on November 27, 2011

Yeah, if the pain has a strong inflammatory component, then acetaminophen isn't the right drug for the job. That's why no one takes it for either form of arthritis. Unless they don't know better, anyway.

That's the problem, either they or their docs don't know that...
posted by ssmug at 3:33 PM on November 27, 2011

whoops..

I found this, which references a past link but doesn't support it...
posted by deliquescent at 3:34 PM on November 27, 2011

The dangers of accidental paracetamol/acetaminophen overdose were well publicized in the UK where I grew up, but I had no idea that the ibuprofen I've been taking instead can cause cumulative kidney damage.

Is there any major downside to acetylsalicylic acid, ie actual aspirin? I know it can make your stomach bleed, like all NSAIDs, but that's not so bad.
posted by w0mbat at 3:46 PM on November 27, 2011

I think the bigger problem is when they put acetaminophen in other OTC medications, like Nyquil or other cold/flu/cough medicines. You take them for your cough, then you get a headache and, not thinking, you pop a couple of Tylenol. It can be really easy to get a lot more acetaminophen than you realize this way.
posted by Weeping_angel at 3:54 PM on November 27, 2011 [5 favorites]

Curcumin/turmeric is a potent selective COX2 inhibitor with loads of clinical research...

The one or two papers I can find that aren't mired in paywall hell, suggests taht while diferuloylmethane inhibits cyclooxygenase it also inhibits a ton of other things at µM concentrations (which isn't exactly selective or especially potent). I can't find any good bio-assay data on this, though, and trying to do a Google search puts me in a land where magnetic copper healing bracelets are hard science.

Got a good solid cite for this?
posted by Kid Charlemagne at 3:55 PM on November 27, 2011 [2 favorites]

This is entirely avoiding his point and is misleading in its implication that it refutes it.

I thought BP meant all acetaminophen when he said "this stuff.". He clarified that he meant using it as an adulterant, which I tend to agree with. If synergy is important then patients could be prescribed both separately, if they weren't at risk for acetaminophen toxicity.

Ha ha ha, Colitis sufferer here, and let me tell you using tylenol for colitis pain is like using a band-aid for amputation

Some Crohn's and colitis patients find it adequate for non-flare-up pain, and as I said it's also useful for regular pain and fever.
posted by jedicus at 4:51 PM on November 27, 2011

I used aspirin for years until I developed GERD-like symptoms recently; not surprised if the two are linked (my GP alluded to this). I took two adult-strength sometimes at night without any food and apparently this is not a good move. Aspirin is great for just about everything except for your digestive tract!

Doc told me to switch to acetaminophen, and I take two capsules (whatever the adult recommended single dose is) when I need it, which isn't often. If I have a cold with headache or some other minor ailment, I take it more often per day.

I consider this post to be a good reminder to be careful; thanks for posting, hat_eater.
posted by Currer Belfry at 4:53 PM on November 27, 2011 [1 favorite]

Liver damage from acetaminophen is most likely to be present if alcohol is consumed simultaneously. Want a cheap way to off yourself? Bottle of extra-strength Tylenol and a six-pack of beer. I know this to be at least one successful way to end your life, because I saw the health insurance claims for the patient who later died from this combination.
posted by PuppyCat at 5:18 PM on November 27, 2011 [1 favorite]

There's a correlation between long-term, heavy use of iboprofen and pancreatic cancer.
They have also found a link between ibuprofen use and kidney cancer. I found this out after I was diagnosed and I used ibuprofen a lot for chronic pain prior to my diagnosis. There is no proof that is why I had kidney cancer, but I'm sure that was part of the reason for it.
posted by SuzySmith at 5:38 PM on November 27, 2011

[Just a reminder, "fuck you" is not the level of discourse we're aiming for here. That said, Decani, please make a greater effort to appear not to be baiting people for sport. ]
posted by restless_nomad at 6:06 PM on November 27, 2011

Yeah, if the pain has a strong inflammatory component, then acetaminophen isn't the right drug for the job. That's why no one takes it for either form of arthritis. Unless they don't know better, anyway.

Interesting you should mention that. I was just reading a paper describing a series of n-of-1 trials (which are pretty interesting in their own right) on acetaminophen vs. celecoxib for osteoarthritis, and it found that for 80% of people, there was no difference in pain relief between the two. So I think it's a bit disingenuous to say that no one uses acetaminophen unless they don't know what they're doing. Granted, it wasn't necessarily the point of the trial to figure out which is better, and there's no measure of baseline pain severity that I can see in the paper, but the point still remains.

Also, as for the link between ibuprofen and pancreatic cancer, the link seems really tenuous. The only thing that seems consistent is that aspirin generally decreases the risk of developing cancer.
posted by greatgefilte at 6:12 PM on November 27, 2011 [3 favorites]

>Do you take it in order to sleep? Because you can buy the sleep ingredient of the pill without the pain reliever part.<

Isn’t it just benadryl? We get the generics.
posted by bongo_x at 6:17 PM on November 27, 2011 [1 favorite]

They have also found a link between ibuprofen use and kidney cancer. I found this out after I was diagnosed and I used ibuprofen a lot for chronic pain prior to my diagnosis. There is no proof that is why I had kidney cancer, but I'm sure that was part of the reason for it.

I don't mean to diminish what you've gone through, but I also don't think it's worth blaming the ibuprofen for your kidney cancer: the increased risk is really quite small. To quote the paper that estimates the risk involved, "assuming a causal relation, use of nonaspirin NSAIDs [e.g. ibuprofen] by each of 10,929 women or 9,158 men would lead to 1 RCC [renal cell carcinoma] case." So, out of 10,000 people taking NSAIDs regularly, we would expect one to develop kidney cancer over and above the rate of kidney cancer in the general population. Were you that one in 10,000? Maybe, but there's no way to prove it one way or the other.
posted by greatgefilte at 6:27 PM on November 27, 2011

This thread is really interesting - thanks to rumposinc and others for the advice, links and discussions.
posted by odinsdream at 6:50 PM on November 27, 2011 [1 favorite]

Because providers are sensitive to what they perceive to be "drug seeking behavior", which signifies addicts.

I know the "the look" well.
Whenever I go to the doctor for some sort of non-specific pain (usually because I pulled or tore something), they inevitably pull out the prescription pad for Vicodin.
When I start explaining that, for whatever reason, Vicodin doesn't do squat for me and we should just start with something strong from the get-go, I can see in their faces that they're thinking they missed something, and just got conned by someone looking to score.
It doesn't help that I don't have a regular doctor, and just call up to get the next available appointment from the group, whoever it might be.

I can imagine how incredibly frustrating and humiliating it must be for someone who really needs the medication.
posted by madajb at 7:11 PM on November 27, 2011 [2 favorites]

Codeine used to be available over the counter in the U.S, but everybody become opioid junkies so they had to change that.

Michelle Leonhart always sez "Better dead than high! And good luck with that liver transplant!"
posted by mrhappy at 7:48 PM on November 27, 2011 [2 favorites]

I'd like to know why naproxen gets so little love from doctors. No risk of liver failure like Tylenol, no risk of upset stomach like ibuprofen, no risk of Reyes like aspirin. And it's really effective and cheap!
posted by miyabo at 7:49 PM on November 27, 2011

I'd like to know why naproxen gets so little love from doctors. No risk of liver failure like Tylenol, no risk of upset stomach like ibuprofen, no risk of Reyes like aspirin. And it's really effective and cheap!

I think you should probably go back and check on this. There's always going to be individual variation, but naproxen carries the same general risk profile as other COX-1 inhibitor NSAIDs.

As someone advised to avoid NSAIDs due to GI complications, I'm stuck using oral steroids, analgesics and opioids to manage inflammation and pain. I too would prefer not having my meds 'pre-combined' so that my doctors and I can optimise dosing of each component.
posted by michswiss at 8:04 PM on November 27, 2011 [1 favorite]

I've always been medication-shy, and never really took Tylenol and such after becoming an adult (ie when my mother stopped determining the medications I took.) At 40, this year, while suffering a sinus-like headache for several days, I started taking acetaminophen, just one pill a day from the first aid kit at work, and it worked wonders. I briefly thought I was foolish to be so med-shy, when such a convenient and effective pain relief solution was so close at hand, and with none of the gastric side effects of ibuprofen (which rips my intestines apart, figuratively.)

After reading this thread, I think I'll go back to my med-shy ways (when it comes to relieving symptoms, that is.)
posted by davejay at 8:41 PM on November 27, 2011

I live in mortal fear of accidentally overdosing. I have prescription pain pills, and though I take "days off" when I don't have to do anything other than lay around the house and study, I have to take the pain pills to do anything other than lay around my house. Because I'm trying to get through school, and get a good job, in spite of disabling arthritis, I'm forced to take prescription pain pills with tylenol.

I have family members in the medical profession. I've seen first-hand how ugly a Tylenol overdose can be. But I still forget sometimes: "Oh crap, I'm still hurting...wait, did I take that pill I intended to take five minutes ago? I'm not sure." I'm stressed and physically pushing the limits of my endurance, so my memory is crap, especially for small gestures that I do regularly...like taking a pill.

I fight it by trying to put my day's allotment into a pillcase, and only taking pain pills from the case. And I mix them. I put in ibuprofen, and prescription pills that mix codeine with tylenol. On a good day there will be some of each left over for the next day. Sometimes the pill case isn't always on my person, and I again run into the problem of forgetting what I've taken.

The one accidental overdose case I saw was someone who had taken too much cold medication that already had tylenol, in conjunction with tylenol.

It really makes me angry that they mix codeine with tylenol. It makes my life more hellish. Sure they work well together. But I'm perfectly capable of taking one pill of each. I'd give the world to not have to take either, but that's not possible.

Also, to this comment:

Overall, though, if 4G/day isn't enough for patients' pain, then their docs need to brush up on their pain management treatment and consider alternatives.

I say, tell that to someone with health insurance. Also, the alternatives are generally shitty for someone with serious chronic pain even when you do have insurance, at least here in the US. Doctors are afraid to prescribe, alternative treatments don't work worth a damn, and insurance won't cover them.

I try to stay at 3gm of Tylenol and when my prescription pain pills run out for the month, as they sometimes do, I very rapidly hit that 3gm limit, if I leave my house and attempt to actually live my life. And hell, forget about a social life. By five p.m. all you want to do is crawl into a bathtub filled with ice.

And don't get me started on the paternalistic behaviour of the state and the doctors who are paranoid about drug-seeking patients and on what they base their decisions. Among other things, they're more reluctant to prescribe to someone who's depressed, even if you're depressed because you hurt so bad all the time you can barely think and you have no money and in order to fix the money situation you have to drag your body through day after day after day.
posted by thelastcamel at 8:43 PM on November 27, 2011 [3 favorites]

I'd like to know why naproxen gets so little love from doctors. No risk of liver failure like Tylenol, no risk of upset stomach like ibuprofen, no risk of Reyes like aspirin. And it's really effective and cheap!

Oh, god, my dentist put me on this after a root canal, and after one single dose, I felt terrible (gastrically) for almost a week. No risk of upset stomach my ass.
posted by davejay at 8:43 PM on November 27, 2011 [1 favorite]

If a patient would benefit from a combo drug then they can get two prescriptions instead of one. I have to specifically request standalone pain drugs or else I get the evil acetominophen laced evil kind. Other than paternalistic punishment there is no justification for including acetominophen with other drugs.

A relative of mine just died of liver failure because of this. An accident on the job a few years ago plunged him into painkiller addiction and alcoholism. Alcohol + painkillers destroyed his liver. The doctors did warn him and our family kept putting him in rehab centers, but the addiction won out in the end. Maybe he never would have gotten clean, but the acetominophen was an extra unnecessary bullet in the gun that shortened his chances to get clean.
posted by melissam at 9:01 PM on November 27, 2011 [1 favorite]

The only thing that seems consistent is that aspirin generally decreases the risk of developing cancer.

And heart disease, both of which are hypothesized to be inflammation dependent.

In fact, I've heard is said that there are many who believe that the increased incidence of heart attacks observed in people switching to selective COX2 inhibitors might be due to their stopping aspirin therapy and something to do with COX 1, particularly since Vioxx (the one that was removed from the market) bound COX2 with a much greater affinity than COX1 vs. Searle's Celebrex (which is still available).

The person who suggested it didn't seem to get why it would be unethical to do a controlled experiment to test this hypothesis, though, so the idea lost some cred in my mind by association.
posted by Kid Charlemagne at 9:17 PM on November 27, 2011

This is why I just smoke a joint and take a shot of bourbon when I have a headache.
posted by furiousxgeorge at 9:18 PM on November 27, 2011 [3 favorites]

I'd like to know why naproxen gets so little love from doctors. No risk of liver failure like Tylenol, no risk of upset stomach like ibuprofen, no risk of Reyes like aspirin. And it's really effective and cheap!

Naproxen getting so little love?!?!?! They fucking love scripting that stuff. For your information, Naproxen can cause gastrointestinal tract issues... I would know from first hand experience. Just a little TMI, I never knew what shitting blood was prior to that and Mobic, and I really never wanted to experience that. Good ol' opiate scripts never do that (in fact the opposite, but I'd rather have that in comparison to a consistently upset stomach with fucked bowl movements), with the added benefit of actually addressing my pain.
posted by handbanana at 9:51 PM on November 27, 2011 [1 favorite]

There is cyanide in lima beans

I knew it! My mother was trying to kill me when I was a kid!
posted by deborah at 9:53 PM on November 27, 2011 [3 favorites]

This study is has several problems that should keep anyone from worrying too much about the results.

First, this is a study with only a numerator: patients sick enough to be admitted to a specialised liver centre. How many other patients had taken the same amount of "staggered overdose" and didn't develop any liver problems at all? The denominator could be almost zero or it could be tens of thousands of patients, this study has no way of finding that number out.


Second, the study has problems with the gold standard used to diagnose the cause of the liver failure. The authors ascribe the cause of the liver failure to acetaminophen if Hepatitis A and B, autoimmune hepatitis, and Wilson's Disease were excluded

AND

1)at any time in the 7 days before presentation the patient gave a history of ingestion of > 4 grams of acetaminophen, because that is a "potentially toxic" dose of acetaminophen. (But this is using circular reasoning: if a patient were to develop liver failure from another, unknown cause and to take the acetaminophen at a high dose because they were feeling so bad the liver failure would be falsely ascribed to the acetaminophen.)

or

2)serum acetaminophen levels were >10mg/L. (But liver failure can cause falsely elevated acetaminophen levels on the assay most commonly used to check these levels, Elevated acetaminophen level: Could it be a red herring?.)

or

3)serum ALT level > 1000 IU/L (Which again is a bit of circular reasoning: patients known to have taken a toxic dose of acetaminophen and who develop liver failure often develop such a high ALT level [Liver enzyme alteration: a guide for clinicians]; other causes of such a high level other than Hep A & B and autoimmune hepatitis are rare; so if the level is this high it must be due to acetaminophen. But what if the patients with a staggered overdose were sicker at baseline and more likely to have had hypotension causing a "shock liver" which is another cause high ALT elevations?)

Third, the "staggered overdose" patients were sicker at baseline, they were older, more likely to chronically abuse alcohol and more likely to be encephalopathic on presentation.

Take home message: don't worry about giving yourself liver failure if you take 4 grams of acetaminophen a day.
posted by v-tach at 10:01 PM on November 27, 2011

On a more serious note: I'm diabetic. I had been taking ibuprofen (Advil) for headaches, etc. but found out that it's processed through my kidneys. That's not a good idea for a diabetic and my doctor never told me. Now I take Extra Strength Tylenol three at a time. Two does nothing for me, three does the job. Which begs the question - what's a real dose? One might work for some people, three or even four for other people.

Everyone should educate themselves, especially the people with ongoing health issues. Threads like this and the articles posted help the uniformed. Some of the stated "facts" may be overstated a bit, but it never hurts to be a little paranoid about your health.
posted by deborah at 10:07 PM on November 27, 2011 [1 favorite]

…or what Poet_Lariat said above.
posted by v-tach at 10:11 PM on November 27, 2011

Hey, Ivan Fyodorovich, I remember a story linked from here about a guy who became a recreational "poppyseed tea" drinker. It sounded trivially easy the way he described it to buy large bulk orders of "decorative seed pods" online, and brew up opium tea from that.

If you really are having a big problem with your pain that sounds to me like a feasible end run around the health care system.
posted by Meatbomb at 10:46 PM on November 27, 2011

Jail hurts worse.
posted by furiousxgeorge at 10:57 PM on November 27, 2011

That was not a fun story. His whole life came to revolve around acquiring and processing the tea materials, which could get cracked down upon at any moment, and apparently eating/drinking opium makes withdrawal worse.
posted by Adventurer at 11:07 PM on November 27, 2011 [1 favorite]

The FDA has moved to eliminate several combination acetaminophen/opioid medications, as well as reduce the maximum recommended doses of acetaminophen (APAP):

http://www.msnbc.msn.com/id/31664450/ns/health-health_care/t/fda-panel-votes-eliminate-vicodin-percocet/

While I think in general this is a great idea, this will have the unfortunate effect of eliminating Vicodin (5 mg hydrocodone/500 mg APAP), which is a DEA class III drug. The trouble is that hydrocodone tablets are DAE Class II, which is a Much Bigger Hassle.

In my practice, I am severely hamstrung by the fact that there are
A) very few opioid tablets that do not also contain acetaminophen
B) very few systematic comparisons of various oral medications' efficacy against acute postsurgical pain. Is vicodin > naproxen > APAP alone? Very hard to figure out.

For example, I routinely give two vicodin tablets (10 mg hydrocodone/1000 mg APAP) to patients who are just "waking up" from surgery. I have given thousands of doses, and it helped most of those patients to some degree. Frequently, though, I would like to be able to give more hydrocodone and less APAP, but there's no way for me to do so, given the constraints of my hospital's formulary.

We may soon be getting IV acetaminophen for surgical patients - this will be very helpful!
posted by etherist at 11:30 PM on November 27, 2011 [3 favorites]

Also ... if you have more than one doctor: say an MD for your physical health and a psychiatrist for your mental health talk to both of them about side effects of any new medication.

Last year I hurt my shoulder, badly. Vicodin-like medications give me horrible nausea. So I was prescribed Tramadol. Which I thought worked great. I'm also bipolar, and Tramadol is definitely contraindicated when taking some of the meds I'm on for that. Coming down off of that shit after three months caused me to have convulsions that were very worrying. Had I, or either of my doctors, had talked together about this, it wouldn't have happened at all.

Doctors hand out pill like candy. We take them like candy. We could all be informed better.
posted by PapaLobo at 11:31 PM on November 27, 2011 [1 favorite]

I used to hardly ever pills. Now due to arthritis, I have naproxen which incidentally, if you read label is bad for your stomach. I also have lactose intolerance IBS. I wish it were just actually legal to have dope. It's far safer. My anti-depressant is causing hair loss. I am at a point if wanting to see if there is something I could have that doesn't cause hair loss. My medications all can hit me in the liver and kidneys far worse than an occasional glass of rakija would.
I wonder just when we can over-throw the Puritans?
posted by Katjusa Roquette at 11:46 PM on November 27, 2011 [3 favorites]

It would make sense to combine it in pills like percocet, as it is desirable to try to limit an individual's intake of opioids

Oh really? Is it more desirable to cause permanent liver damage than let someone possibly abuse a drug, just a little bit?

Also, pretty much any drug-related deaths are absolutely eclipsed due to deaths related to alcohol abuse. Granted, alcohol already causes liver damage after extensive usage, but I don't see anyone making any efforts to make it more lethal in order to discourage drinking. Not only because alcohol continues to be the one of the most-sanctioned death-causers in the US (probably after cars, and even then alcohol plays a helpful role!) but also because it's generally recognized that if people are going to drink too much, they're going to drink too much, and there really aren't any tricks out there to prevent them from doing so.

Why then the crazy attitude about painkillers, that somehow making them lethal will keep people from (ha ha) "hurting themselves".

Sheesh.
posted by Deathalicious at 6:25 AM on November 28, 2011 [4 favorites]

often develop such a high ALT level [Liver enzyme alteration: a guide for clinicians]; other causes of such a high level other than Hep A & B and autoimmune hepatitis are rare;

A bit of a correction here regarding ALT levels and liver issues. Your statement above is very dependent on what target group that you are in. For instance, a recent (within several years) V.A. study found that roughly 30% of Vietnam era Vets were testing positive for Hep-C.

The more you know....
posted by Poet_Lariat at 8:18 AM on November 28, 2011

Paraphrasing a comment I made in an older, tangentially related thread...

The UK introduced "blister packs" of painkillers to replace the easily guzzleable bottles of tablets in a successful attempt to reduce suicides by painkillers and the most common outcome of these suicide attempts: non-lethal but severe organ damage.
posted by NailsTheCat at 11:44 AM on November 28, 2011 [1 favorite]

>> I remember a story linked from here about a guy who became a recreational "poppyseed tea" drinker.

> That was not a fun story. His whole life came to revolve around acquiring and processing the tea materials

A few hours later, I had drunk the salt of 200 pods but only felt a kind of necessary doom. I got out of bed and looked in the mirror to make sure I was still there. I looked like that mug shot of Nick Nolte, my hair up in the air, pasted in place by sweat and spilled drink. Tiny poppy seeds were stuck to my shirt. They were everywhere. In the bed. Under my feet. On the floor.

> 2.7 gram daily maximum

What?!?

Tylenol's "new" dosing is 2 500mg tablets every 6 hours, max 3x per day. It used to be every 4-6, max 4x per day. That's a change from 4g/day to 3g/day. Target's generic acetaminophen in the U.S. comes with the same instructions.
posted by morganw at 12:20 PM on November 28, 2011

Deathalicious - i responded to this above. It has nothing to do with stopping abuse, it is beneficial because people may have a legitimate improvement in pain relief using a combined pills. Which is desirable because, as I've noted above, deaths due to prescription opiates are increasing at an alarming rate, so if you can use the synergistic effect of acetaminophen with an opiate to provide the pain relief needed while decreasing the total dose of narcotics, that would be a good thing.

I really do not believe that anyone thought "liver failure! That'll stop prescription drug abuse!"
posted by deliquescent at 2:08 PM on November 28, 2011

You will cause damage faster with acetaminophen than with opiates. And if you seriously think no one thought liver damage is an appropriate punishment for getting high, you haven't paid attention to the drug war.
posted by spaltavian at 6:07 PM on November 28, 2011 [1 favorite]

I was just about to switch to aspirin (literally in the drug store about to pick up the bottle) when I remembered that it is the only NSAID that is known to be a trigger for gout. There is no way in hell I'm risking a repeat of the one-off gout attack I had last year. Looks like every silver lining has a cloud.
posted by w0mbat at 4:06 PM on December 8, 2011

Painkiller 10 times stronger than Vicodin worries addiction experts
posted by homunculus at 3:19 PM on December 26, 2011

Pain Patient Advocate Siobhan Reynolds Dies in Plane Crash
posted by homunculus at 3:23 PM on December 26, 2011

Oh, hell.

Both Siobhan Reynolds, and her late husband Sean Greenwood, were fellow alumnae of mine from St. John's College, both of the Santa Fe campus, where Greenwood was an undergrad and Reynolds was a GI. This hasn't even been posted to any of the alumni mailing lists; it's odd that I'd see this on MeFi first.

This is the rare kind of thing that actually tweaks the few conspiracy-minded instincts I have. Siobhan made quite a few enemies in law enforcement, especially among district attorneys and the DEA when she defended physicians who she felt were unfairly targeted for prosecution. Her Pain Relief Network did some great work—this Slate article discusses some of this and some pretty amazing harassment she received from law enforcement.

This is sad.
posted by Ivan Fyodorovich at 3:35 PM on December 26, 2011 [1 favorite]

It is sad, and I'm sorry to be the bearer of bad news. Radley Balko has a tribute to her here.
posted by homunculus at 6:17 PM on December 26, 2011