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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.? 126.96.36.199 (talk) 06:24, 27 December 2008 (UTC)
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." 
We urgently need a reference for this
- 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.
- Which links to PMID 16317692 and PMID 11157536. Mr Bungle | talk 05:38, 17 July 2009 (UTC)
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)
- Warnings Sought for Popular Painkiller By Sheryl Gay Stolberg, New York Times, Published: September 20, 2002
- Cite error: The named reference
pmid17984051was invoked but never defined (see the help page).
- Awareness: Too Much Acetaminophen? Few Seem to Know, By Nicholas Bakalar, New York Times, February 27, 2007
- Cite error: The named reference
Drug-Induced_Hepatotoxicitywas invoked but never defined (see the help page).
- Tylenol Toxicity, Medicinenet.com]
- Tylenol Overdoses Linked To Acute Failure of Liver, by Denise Grady, The New York Times, October 16, 1997,
- What you don't know about Tylenol can kill you, By Dr. W. Gifford Jones, Canadian Free Press, September 8, 2003
- Lee M (1998). "Acute Renal Failure in an Alcoholic Taking Acetaminophen". Journal of the American Board of Family Practice. 11 (5): 410–13. unknown.
- PERSONAL HEALTH; With Tylenol and Children, Overdosing Is Perilously Easy By Jane E. Brody, New York Times, January 25, 2000
- High doses of Tylenol are linked to liver damage, by Denise Gellene, Los Angeles Times, July 5, 2006
- High Tylenol Doses Linked to Liver Woes By Carla K. Johnson, Washington Post (AP) Tuesday, July 4, 2006
- Mixing Tylenol With Caffeine may Increase the Risk of Liver Damage, Study Finds, By Tina Benitez, September 27, 2007, Fox News
- Caffeine Plus Acetaminophen Toxic for Some,By Steven Reinberg, Washington Post, September 26, 2007
- Acetaminophen (Tylenol) Poisoning WebMD.com
- Aches, Pains and Warning Labels By William M. Lee, New York Times, March 17, 2004]
- Poisonings From a Popular Pain Reliever Are Rising, By Deborah Franklin, New York Times, November 29, 2005
- Tylenol.com warning at manufacturer website.