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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)
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)
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)
I removed the fallowing from Tylenol and it should be reincorporated here
Acetaminophen causes three times as many cases of liver failure as all other drugs combined, [1] and is the most common cause of acute liver failure in the United States, [2] [3] accounting for 39% of cases. While it occurs through overdosing [4], even recommended doses especially combined with even small amounts of alcohol, have caused irreversible liver failure. [5] [6]
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. [7]
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. [8] In infants and small children, studies have indicated that the toxic dose is less than twice the recommended dose. [9].
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. [10] 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..." [11]
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. [12]. 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," [13]
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. [14] Due to the delayed symptoms and the importance of immediate treatment, overdoses of acetaminophen kill about 12% of those who seek treatment. [5] 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. [15] 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. [16] The manufacturers of Tylenol recommend, "You should not take two or more products that contain acetaminophen at the same time." [17]
References
pmid17984051
was invoked but never defined (see the
help page).Drug-Induced Hepatotoxicity
was invoked but never defined (see the
help page).-- Scientus ( talk) 07:18, 8 April 2009 (UTC)
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)
in both the United States and the United Kingdom it is the most common cause of acute liver failure.[70][71]
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)
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)
This text was added by Mr Bungle in an edit dating back to 23:54, 20 November 2008.
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)
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)
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)
Information on overdose in the Paracetamol article seems to be more thorough and accurate.
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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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)
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)
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)
![]() | Paracetamol poisoning has been listed as one of the Natural sciences good articles under the good article criteria. If you can improve it further, please do so. If it no longer meets these criteria, you can reassess it. | ||||||||||||
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Current status: Good article |
![]() | This article is rated GA-class on Wikipedia's
content assessment scale. It is of interest to the following WikiProjects: | |||||||||||||||||||||||
|
![]() | Ideal sources for Wikipedia's health content are defined in the guideline
Wikipedia:Identifying reliable sources (medicine) and are typically
review articles. Here are links to possibly useful sources of information about Paracetamol poisoning.
|
![]() | This article links to one or more target anchors that no longer exist.
Please help fix the broken anchors. You can remove this template after fixing the problems. |
Reporting errors |
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)
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)
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)
I removed the fallowing from Tylenol and it should be reincorporated here
Acetaminophen causes three times as many cases of liver failure as all other drugs combined, [1] and is the most common cause of acute liver failure in the United States, [2] [3] accounting for 39% of cases. While it occurs through overdosing [4], even recommended doses especially combined with even small amounts of alcohol, have caused irreversible liver failure. [5] [6]
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. [7]
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. [8] In infants and small children, studies have indicated that the toxic dose is less than twice the recommended dose. [9].
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. [10] 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..." [11]
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. [12]. 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," [13]
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. [14] Due to the delayed symptoms and the importance of immediate treatment, overdoses of acetaminophen kill about 12% of those who seek treatment. [5] 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. [15] 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. [16] The manufacturers of Tylenol recommend, "You should not take two or more products that contain acetaminophen at the same time." [17]
References
pmid17984051
was invoked but never defined (see the
help page).Drug-Induced Hepatotoxicity
was invoked but never defined (see the
help page).-- Scientus ( talk) 07:18, 8 April 2009 (UTC)
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)
in both the United States and the United Kingdom it is the most common cause of acute liver failure.[70][71]
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)
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)
This text was added by Mr Bungle in an edit dating back to 23:54, 20 November 2008.
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)
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)
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)
Information on overdose in the Paracetamol article seems to be more thorough and accurate.
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)
Hello fellow Wikipedians,
I have just modified one external link on Paracetamol poisoning. Please take a moment to review my edit. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit this simple FaQ for additional information. I made the following changes:
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Cheers.— InternetArchiveBot ( Report bug) 14:25, 29 January 2018 (UTC)
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)
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)
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)