Talk:Paracetamol poisoning

No discussion of long-term toxicity

This article should really be called "Paracetamol overdosing" because that's all it discusses. There's no discussion of long-term paracetamol toxicity e.g. https://www.nhs.uk/news/medication/is-long-term-paracetamol-use-not-as-safe-as-we-thought/. This can be found in those suffering from chronic pain who are unable to take any other painkiller because of stomach issues, for example, or amongst dementia sufferers who regularly take more than the recommended amount because they're unable to dose correctly because of memory impairment. I would like to see this article expanded and restructured to take into account these other kinds of paracetamol toxicity scenarios. — Preceding unsigned comment added by 2.98.39.95 (talk) 12:19, 28 December 2018 (UTC)

Toxicity or hepatotoxicity?

This article almost exclusively discusses paracetamol's toxic effects on the liver (hepatotoxicity), which is why when I split the content from Paracetamol, I initially called the article Paracetamol hepatotoxicity. This was changed recently with good intentions, but I still feel hepatotoxicity is more appropriate. Paracetamol's toxicity to other organs is discussed elsewhere, for example, at Analgesic nephropathy. --David Iberri (talk) 01:10, 6 November 2008 (UTC)

I just thought I'd be bold and change it as to me it seemed to fit better being toxicity rather than hepatotoxicity. I sort of thought that toxicity better covered the earlier effects (if present, i.e. coma, metabolic acidosis) and sometimes there is kidney damage alongside liver damage due to overdose as well. I also thought about paracetamol overdose or paracetamol poisoning as a title (I think they both redirect here) as liver damage is almost always due to an overdose rather than an adverse effect at normal doses. I'm not too worried which is used I just thought toxicity was slightly more broad and better defined what happens in overdose situations. Mr Bungle | talk 02:28, 6 November 2008 (UTC)

I agree that this article should not repeat information found in Analgesic nephropathy. But that article explicitly states that it is about liver toxicity, while this one does not. Before there can be an article about hepatotoxicity, there needs to be a parent article that discusses toxicity in general, for this article to be encyclopedic. Since the non-liver portion of this article is small but important, I'd favor keeping the article under its new name. — trlkly 12:05, 21 December 2008 (UTC)

Toxicity by route of administration?

Since it is toxicity based on the liver, do methods of administration change the toxicity, meaning, would it not taken orally but in a way that skips first-pass metabolism (a way other than oral/digested) affect this in any way? If not the article should say so, if so the article should really say so. So would this reduce or negate the heptatotoxicity to any degree? IV? liquid rectal suppository? etc.? 4.242.192.84 (talk) 06:24, 27 December 2008 (UTC)

While po APAP definitely has the highest risk of hepatotoxicity, IV APAP is also hepatotoxic (albeit less so, theoretically, for the reason you mentioned above). See: Jahr JS, Lee VK. Intravenous acetaminophen. Anesthesiol Clin. 2010;28(4):619–645. Biochemistry&Love (talk) 19:47, 21 April 2017 (UTC)

from Tylenol#Dangers

I removed the fallowing from Tylenol and it should be reincorporated here

Main article: Paracetamol toxicity

Acetaminophen causes three times as many cases of liver failure as all other drugs combined, and is the most common cause of acute liver failure in the United States, accounting for 39% of cases. While it occurs through overdosing, even recommended doses especially combined with even small amounts of alcohol, have caused irreversible liver failure.

Acetaminophen is metabolized in the liver, resulting in a by-product, N-acetyl-p-benzoquinone imine (NAPQI), that can damage liver cells, but is typically converted into a harmless substance by an antioxidant glutathione. However, large doses of acetaminophen overwhelms the body's supply of glutathione, resulting in destruction of the liver cells.

People who have the highest risk for Acetaminophen related kidney failure include: heavy drinkers (three or more drinks per day), elderly men, and persons with pre-existing liver or kidney damage. In infants and small children, studies have indicated that the toxic dose is less than twice the recommended dose..

A study published by the Journal of the American Medical Association in 2006 suggests problems even in healthy people taking the pain reliever as directed. Healthy adults taking maximum doses of Tylenol for two weeks had abnormal liver test results. Dr. Neil Kaplowitz of the University of Southern California, co-author of the study, said, "I would urge the public not to exceed four grams a day. This is a drug that has a rather narrow safety window..."

According to a preliminary study conducted by the University of Washington, mixing acetaminophen and caffeine may cause liver damage, especially in heavy caffeine drinkers. Researchers discovered that caffeine can triple the amount of N-acetyl-p-benzoquinone imine (NAPQI), the dangerous by-product which destroys liver cells. . This reaction can also be caused by large doses of painkillers that combine caffeine and acetaminophen (e.g., Anacin, Excedrin & Midol). These products are often used to treat migraines and menstrual discomfort. Dr. Sid Nelson, a professor of medicinal chemistry at the University of Washington said, "Caffeine can interact with an enzyme that can form a toxic metabolite of acetaminophen in such a way that it increases the formation of that toxic metabolite,"

Symptoms from an overdose of acetaminophen typically appear after 24 hours, or in some cases up to 48 hours; however, getting immediate treatment prior to symptoms occurring, can greatly improve the outcome. The antidote to acetaminophen overdose, N-acetylcysteine (NAC), is most effective when taken within eight-hours of an overdose. Due to the delayed symptoms and the importance of immediate treatment, overdoses of acetaminophen kill about 12% of those who seek treatment. Typical symptoms range from nausea and malaise to extreme upper abdominal pain in the region of the liver.

Tylenol is only one among many popular medications containing acetaminophen, but few users realize that it is contained in hundreds of other pain relievers and cold remedies, and that combined usage has a cumulative effect. Fifteen percent of accidental overdoses involve the simultaneous use of more than one product containing acetaminophen. Products from common brands include acetaminophen: Excedrin, Midol, Theraflu, Alka-Seltzer and NyQuil, as well as prescription narcotics such as Vicodin and Percocet. Following the recommended dosages for each, but in combination can far exceed safe limits for acetaminophen intake. The manufacturers of Tylenol recommend, "You should not take two or more products that contain acetaminophen at the same time."

References

-- Scientus (talk) 07:18, 8 April 2009 (UTC)

We urgently need a reference for this

Paracetamol is the number one cause of acute liver failure in the US. We need a ref for this fact. MaxPont (talk) 08:11, 16 July 2009 (UTC)

It is referenced in the Epidemiology section:

in both the United States and the United Kingdom it is the most common cause of acute liver failure.[70][71]

Which links to PMID 16317692 and PMID 11157536. Mr Bungle | talk 05:38, 17 July 2009 (UTC)

I think it is important enough to be mentioned in the Lead section. MaxPont (talk) 07:36, 17 July 2009 (UTC)

Fair enough, will repeat them in the lead :) - Cheers Mr Bungle | talk 07:53, 17 July 2009 (UTC)

Unnecessary quote?

In the Risk factors section, there is a quote from Dr. Sid Nelson which, in my opinion, does not add to the topic at hand (i.e. the resulting toxicity of paracetamol when taken with high doses of caffeine). The quote is the following (along with introductory sentence): Dr. Sid Nelson, a professor of medicinal chemistry at the University of Washington, said, "Caffeine can interact with an enzyme that can form a toxic metabolite of paracetamol n in such a way that it increases the formation of that toxic metabolite,"

I don't think it is necessary to quote Dr. Nelson's words as they don't provide any information that was not mentioned in the previous sentences (in fact, his words broadly summarize the topic). Anyone agree with me? Cheers, Numero4 (talk) 06:57, 5 March 2010 (UTC)

Prescription Opioid (Vicodin, Percocet etc) Abuse

This article should reference prescription opioid abuse and paracetamol related toxicity, I'll look into appropriate references as to percentage of paracetamol ODs involve these drugs.Jlodman (talk) 03:10, 28 February 2011 (UTC)

Only 50,000 overdoses per year

This text was added by Mr Bungle in an edit dating back to 23:54, 20 November 2008.

However, as overdose is a relatively minor problem, for example only 0.08% of the UK population present with paracetamol overdose each year. This contrasts with it being a safe and effective medication taken by millions of people every year.

I'm a bit shocked this hasn't been challenged. If you had 120 drugs with a 0.08% annual overdose rate, 10% of the UK population would be poisoned annually. The source for this is behind a paywall. What proportion of overdose is intentional? It's seems like a large number to me concerning possible liver damage, whether deliberate or not. If just 1% of overdoses lead to liver transplant that works out to 500 transplants a year at a cost of maybe a quarter million each to the UK health care system. We could be talking $100 million per year, depending on how much "just 1%" overstates reality. — MaxEnt 13:43, 17 November 2011 (UTC)

Hey, I had a look at the original paper:

"each year, 0.08% of the UK population are assessed in hospital with paracetamol poisoning and only 0.6% of these patients develop acute liver failure (ALF). Although less common than in the UK, paracetamol overdose is a significant clinical problem in Australia, Denmark and the USA and is the commonest cause of ALF in the USA. Approximately 0.01% of the US population and 0.02% of the Australian population are assessed in hospital each year because of paracetamol poisoning."

Does this help? Mr Bungle | talk 21:34, 17 November 2011 (UTC)

Causes

Strangely, the cause section does not address the elephant in the room. The article should discuss suicidality, other intentional self-harm, misdosing, and other accidental overdoses. Gunnell et alia may be helpful. LeadSongDog come howl! 22:08, 20 December 2016 (UTC)

Added a line on this topic, re: suicidal ideation. Biochemistry&Love (talk) 08:26, 28 December 2016 (UTC)

GA Reassessment

This discussion is transcluded from Talk:Paracetamol toxicity/GA2. The edit link for this section can be used to add comments to the reassessment.

The last GAR was passed by a well known sock in 2008[1]. The article contains content supported by popular press and old primary sources. Also needs an update. Doc James (talk · contribs · email) 19:10, 17 December 2016 (UTC)

Wow, that's a steaming pile of bad sources. This needs a lot of work, but that work is also worth doing. It'll take some time. LeadSongDog come howl! 21:03, 20 December 2016 (UTC)

Yes plan to do some work on it aswell. This is the problem with socks passing GAs.Doc James (talk · contribs · email) 03:53, 21 December 2016 (UTC)

Okay did a major update of the lead. Will leave as keep. Doc James (talk · contribs · email) 16:35, 9 July 2017 (UTC)

Old heading

Information on overdose in the Paracetamol article seems to be more thorough and accurate.

—Preceding unsigned comment added by 12.33.232.124 (talk • contribs) 18:58, 24 July 2006

Good observation, tag adjusted and discussion will be held at Talk:Paracetamol/Archive 2#Merge proposal with Paracetamol poisoning. David Ruben ^Talk 14:54, 19 August 2006 (UTC)

Chicago Tylenol murders

Is linked in the epidemiology section just as it should be. It does not go right at the top. Doc James (talk · contribs · email) 20:11, 9 January 2018 (UTC)

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Methionine and other treatments

The absence of methionine as a possible treatment seems to be a glaring omission. This Cochrane review mentions a few other treatments that have been investigated. Axl ¤ [Talk] 10:33, 16 August 2018 (UTC)

Ah, cysteamine and methionine are mentioned in a single sentence in the "Acetylcysteine" section. Nevertheless, there should be more information about these. This review paper may be helpful, too. Axl ¤ [Talk] 10:39, 16 August 2018 (UTC)

Extent of glutathione depletion required before toxicity arises

There seems to be some confusion in the literature about the degree to which glutathione has to be depleted before toxicity is observed. The Pathophysiology section of this article paraphrases Richardson as saying that depletion to 70% (i.e., by 30%) of the normal amount is sufficient. However, I have found another reference claiming that depletion by 70% is required (What is the role of NAPQI in the pathophysiology of acetaminophen toxicity/poisoning?), and another that suggests that 90% depletion may be required ([2], near the bottom of section 3). — Ah, here's another quoting 70%: [3] (search for "70%").

While the Richardson paper does indeed speak of depletion to 70% — the paraphrase is accurate — I think the paper is probably wrong. For one thing, it just doesn't make sense to me that a 30% drop in the concentration of glutathione would make the half-life of NAPQI so much longer that it would start to do damage. If that were true, the safety margin would be too small for acetaminophen to be a useful medication. Glutathione stores probably vary by more than that between individuals. Also, the second reference above, which goes into much more detail, says that in mouse models, even 70% depletion wasn't clearly sufficient, though 90% was. I lean toward concluding that (a) toxicity sets in somewhere between 70% and 90% depletion, which makes much more sense than 30% from a half-life perspective, and (b) Richardson, or someone somewhere along the line, confused "depletion by" with "depletion to". --ScottBurson (talk) 02:53, 12 October 2019 (UTC)

Fatal dose

I may have missed it, but does the article say what the fatal dose is? Is that a deliberate omission? Chaptagai (talk) 12:07, 7 March 2023 (UTC)