Talk:Paracetamol/Archive 3

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Pushing Ibuprofen?

Why are there so many references to ibuprofen? This article appears to be pushing Ibuprofen over Paracetamol. A 5 minute search brings up countless medical studies that you could easily use to push the position of whichever drug you favored, that argument has no place in this article.

The Ibuprofen page has no similar anti-ibuprofen propaganda and in fact also mentions Paracetamol/Acetaminophen only in the context of selling the reader on how much better it is.

The first 2 headings (and I would argue therefore most prominent) under "Medical Uses" which are "Fever" and "Pain" both read as cleverly worded advertisements for Ibuprofen..

Sjoa (talk) 04:37, 5 August 2011 (UTC)

Possible cause of Alzheimers

Causes of Alzheimer's disease: paracetamol (acetaminophen) today? Amphetamines tomorrow? seems worthy of mention if only because it may be controversial. - Rod57 (talk) 23:54, 11 November 2011 (UTC)

Ref for recently added para under "mechanism of action"

Put in ref The reference to the last sentance in the first paragraph under the headline mechanism of action needs to have the reference incorporated. The full ref is: Andersson DA, Gentry C, Alenmyr L, Killander D, Lewis SE, Andersson A, Bucher B, Galzi J-L, Sterner O, Bevan S, Högestätt ED, Zygmunt PM. TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Δ9-tetrahydrocannabiorcol. Nat Commun, 2011; 2: 551.

The PMID is: 22109525 — Preceding unsigned comment added by 130.235.144.166 (talk) 09:25, 28 November 2011 (UTC)

I've added the inline reference. I'm not a subject-matter expert, so I've copied the ref details with minimal formatting an no {{cite}} template.

Is the "nature communications" in the text "An article in nature communications from a research group in Lund..." the journal Nature Communications? If so, I'll format and link it - or you can (this comment shows how). Mitch Ames (talk) 10:20, 28 November 2011 (UTC)

Acetaminophen or Paracetamol

Are there any Wikipedia guidelines regarding whether this article should be listed under Acetaminophen or Paracetamol? I always thought that en.wikipedia.org favored American English so Acetaminophen would be preferred. — Preceding unsigned comment added by 79.181.111.82 (talk) 16:39, 3 November 2011 (UTC)

Wikipedia is neutral - officially it favours/protects the original language version of the article unless extremely good reasons exist to change - either keeping the article in English or in American. In this case the article must have been in English originally and therefore American spellings/names are secondary. There are Wikipedia guidelines on all these rules - they're boring to read but very useful to help editors avoid mistakes (eg believing that "en.wikipedia.org favored American") — Preceding unsigned comment added by 217.43.214.180 (talk) 05:01, 15 December 2011 (UTC)

Statement unsupported by citation

My problem with this article is within this sentence:

"Combination drugs of paracetamol and strong opioids like morphine have been shown to reduce the amount of opioid used 
and improve analgesic effect as well as discouraging overuse of addictive opioids due to APAP's potentially toxic effects."

I think it not an unfair restatement of this overly long sentence as follows:

Combination drugs of paracetamol and strong opioids like morphine have been shown to 
a.  reduce the amount of opioid used
b.  improve the analgesic effect
c.  discourage the overuse of addictive opioids (due to APAP's potentially toxic effects.)

So the third line c. seems to say that because APAP is toxic and is combined with addictive opiods that discourages the overuse of those addictive opiods. Logically then the implication is that the medical profession when using a combination of drugs A and B needs the threat of the toxicity of drug A to prevent addiction to drug B. Is that really what the cited study says? I think not. The cited Australian study looks at over-the-counter and pharmacist dispensed combinations of aspirin, codeine, dextropropoxyphene, NSAIDS, and paracetamol. Codeine is not generally considered a "strong opiod like morphine". Dextropropoxyphene is used to tread mild pain, but was taken off the market in Europe and the U.S. due to fatal overdoses and arrhythmias, not addiction. The cited study does quote another study that showed:

"Paracetamol or a non-steroidal anti-inflammatory drug (NSAID) given with a strong opioid such as morphine
in a multimodal analgesic regimen for acute pain, reduces the amount of opioid used, improves analgesia 
and reduces the duration of patient-controlled analgesia."

National Health and Medical Research Council. Acute pain management: scientific evidence. 3rd ed. Canberra: NHMRC; 2010.
www.nhmrc.gov.au/publications/synopses/cp104syn.htm [cited 2010 Jul 7]

There is nothing within the cited study about the reduced duration or reduced overuse of addictive opiods in a multimodal analgesic regimen being "due to APAP's potentially toxic effects." Therefore, I would strike "due to APAP's potentially toxic effects." — Preceding unsigned comment added by 98.169.62.144 (talk) 18:31, 15 May 2012 (UTC)

Prenatal and perinatal analgesic exposure and autism: an ecological link

There's a study on the link between autism and Paracetamol. Here a the PDF of the report: http://www.ehjournal.net/content/pdf/1476-069X-12-41.pdf

Here are the conclusions of this study: This ecological analysis identified country-level correlations between indicators of prenatal and perinatal paracetamol exposure and autism/ASD. State level correlation was also identified for the indicator of perinatal paracetamol exposure and autism/ASD. Like all ecological analyses, these data cannot provide strong evidence of causality. However, biologic plausibility is provided by a growing body of experimental and clinical evidence linking paracetamol metabolism to pathways shown to be important in autism and related developmental abnormalities. Taken together, these ecological findings and mechanistic evidence suggest the need for formal study of the role of paracetamol in autism.

--Farmsworth (talk) 15:09, 20 May 2013 (UTC)

Confusing Article on Method of Action

This article starts of saying that APAP is a CNS pain mechanism inhibitor but the section on methodology is entirely about the COX enzymes and anti-inflammatory action. My understanding was that APAP was DEFINITELY NOT an NSAID. Can somebody with knowledge of pharmacology clear this up. — Preceding unsigned comment added by 69.142.244.49 (talk) 13:29, 10 June 2013 (UTC)

"Activated Charcoal" - does it actually work?

The article currently states that: "Activated charcoal can be used to decrease absorption of paracetamol if the patient presents for treatment soon after the overdose"

While this is a common treatment in the emergency departments in the US, I've seen (can't cite them, sorry) reports that this turns out to be more of a feelgood/looksgood procedure without actually helping.

I'm tempted to rewrite the sentence to something like: "activated charcoal is often used in emergency departments in the belief it will decrease absorption".

Thoughts? Thanks

wiki-ny-2007 (talk) 17:14, 6 August 2013 (UTC)

It does appear to work, for example this study specifically looking at apap [1] showed activated charcoal appears to reduce the number of patients who achieve toxic acetaminophen concentrations and thus may reduce the need for treatment and hospital stay. Mr Bungle | talk 05:37, 7 August 2013 (UTC)

carcinogenicity of phenacetin

Changed "unlike coal-tar derived phenacetin" to "unlike phenacetin" in sentence about carcinogenicity of phenacetin. Both coal tar and phenacetin are carcinogenic, but their carcinogenicity is unrelated, and phenacetin is not typically derived from coal tar. The notion that it is with may have come from the old fashioned usage of "coal tar" to describe a broad range of chemicals (e.g. aniline dyes) synthesized from aromatic hydrocarbons found in coal tar that are now made mostly from petroleum. For example Edwin Slosson's popular 1919 book "Creative Chemistry" refers to aniline dyes as coal tar colors.CharlesHBennett (talk) 02:50, 27 August 2013 (UTC)

Inadequate Referencing for Intro Statements re Fatal Dosing

The following statement is made in the intro regarding fatal doses: "While generally safe for use at recommended doses (1,000 mg per single dose and up to 4,000 mg per day for adults),[5] even small overdoses can be fatal. The ratio between fatal doses and therapeutic doses (the therapeutic index) is much smaller than for other over-the-counter painkillers. According to the US Food and Drug Administration as little as 25 percent above the maximum daily dose can cause liver damage when taken over several days.[6]"

The references provided, [5] (http://www.drugs.com/acetaminophen.html) and [6] (http://www.propublica.org/article/tylenol-mcneil-fda-use-only-as-directed) are neither best available sources, nor do they actually provide reference to the information written. [5] lists a recommended maximum dose of 4000mg per day for adults, but does not say "generally safe for use at recommended doses". The phrase "...even small overdoses can be fatal." is not referenced. [6] ProPublica is a journalism "news room", not a scientific journal or authoritative agency - and the article cited does not mention the US FDA giving a possible 25% overdose level, nor does it provide supporting US FDA references. Also, paracetamol is an over-the-counter painkiller, so how can it be negatively contrasted against otc painkillers?

Could someone knowing remove or fix this bit and provide appropriate references? (I couldn't find anything supporting the idea of dangerous or narrow overdosing margins).Smittee (talk) 15:38, 17 November 2013 (UTC) (edit-moved section24.0.133.234 (talk) 13:23, 22 November 2013 (UTC))

This is important because there has been a recent change in recommended dosing (edited/not correct). Also-can anyone point me in the direction of why the UK name of the drug is used?24.0.133.234 (talk) 13:25, 22 November 2013 (UTC)

Trying to clear up some confusion about daily dosing recommendations- here is something from the FDA http://google2.fda.gov/search?q=cache:wz_MTaLYqR8J:www.fda.gov/downloads/drugs/drugsafety/ucm266631.pdf+acetaminophen+2013+daily&client=FDAgov&proxystylesheet=FDAgov&output=xml_no_dtd&site=FDAgov&ie=UTF-8&access=p&oe=UTF-8 .The way that I heard it was, "less", (heard this on a news report), but after looking at the info. it seems like the FDA is increasing the warning label for awareness of the maximum daily dose, and use of alcoholic beverages. The FDA link pertains to safety warnings as far as I can tell. Also the FDA is concerned about multiple sources of the substance which could lead to exceeding the maximum daily dose.24.0.133.234 (talk) 13:53, 22 November 2013 (UTC)

http://www.health.harvard.edu/fhg/updates/overdoing-acetaminophen.shtml The last paragraph is pretty close to the questioned reference above, and it may be more acceptable than ProPublica, but it is from 2009, before the new FDA warning label info. was put into place. "How much is too much?

It’s difficult to pinpoint the amount of acetaminophen that will result in a liver-damaging overdose. People’s reactions vary, depending on the health of their livers, their glutathione levels, and maybe some as-yet-unidentified genetic factors. Some sources say 12,000 mg over a 24-hour period will have toxic effects on the liver of most people. To put that in perspective: you’d have to take 37 regular-strength pills (at 325 mg each) to hit the 12,000-mg mark. But there’s evidence that much lower amounts will harm the liver in some people. According to the FDA working group, the median daily dose associated with the liver injuries recorded in the agency’s adverse event database and in a large liver failure study was 5,000 mg to 7,500 mg. That’s uncomfortably close to 4,000 mg, the current daily limit for safe intake, so the working group recommended lowering it to 3,250 mg, which works out to 10 regular-strength pills a day. We think that’s good advice.

August 2009 update "24.0.133.234 (talk) 14:03, 22 November 2013 (UTC)

Review of COX inhibitor properties

doi:10.1136/ard.2011.200087 is a review of the suspected COX inhibition-related properties of paracetamol. A stronger source on the mechanism of action compared to what we are citing currently. JFW | T@lk 10:55, 11 December 2013 (UTC)

Pro Publica and MEDRS

I am concerned with this articles repetition of ProPublca and NPR’s claim that "acetaminophen, the active ingredient in Tylenol ... kills the most people [of any over-the-counter drug, according to data from the federal government.” My concerns are twofold:

First, MEDRS discourages if not outright prohibits the use the popular press as a source for medical information. The MEDRS page dedicates a full paragraph to this subject, stating among other things that “The popular press is generally not a reliable source for scientific and medical information in articles. Most medical news articles fail to discuss important issues such as evidence quality, costs, and risks versus benefits, and news articles too often convey wrong or misleading information about health care.”

Second, the information conveyed in this particular series of news articles is in conflict with more reliable medical sources. Contrary to the NPR/ProPublica report, acetaminophen does not “kill more people [of any over the counter drug”. In fact, the likely alternative to acetaminophen, NSAIDS, have been estimated by competent medical sources to kill many fold more each year than acetaminophen. According to a 1999 paper by Singh et al (http://www.ncbi.nlm.nih.gov/pubmed/10369853), 103,000 patients were hospitalized for NSAID related GI bleeding in the US in 1998 of which 16,500 died. Another study widely cited in review articles estimated the NSAID-related US hospitalization and mortality rate at 32,000 and 3,200 respectively http://www.ncbi.nlm.nih.gov/pubmed/14704592. While there is considerably discrepancy between these estimates, the lower of the two is still over 20-fold greater than the estimated annual mortality from acetaminophen. The problem appears to be that Pro Publica relied exclusively on poison control center data for its mortality figures. While acetominophen produces an immediately recognizable drug-induced hepatotoxicity, NSAIDs produce gastric bleeding episodes that are associated with chronic use at normal doses. Because overdose is not involved and gastric bleeding has multiple causes, these NSAID related episodes are unlikely to be reported to poison control centers.

The FDA has reviewed acetaminophen risks, and published the conclusions of an internal working group report stating that “We would not want FDA interventions to address the hepatotoxicity risk of acetaminophen to be misinterpreted as an agency position that NSAIDs are safer than acetaminophen. The working group recognizes that NSAIDS, especially with long-term use, result in important gastrointestinal and renal morbidities. The purpose of the interventions is to reduce acetaminophen-related hepatotoxicity, not to decrease appropriate acetaminophen use or to drive people to use NSAIDs instead.” http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/UCM164898.pdf

I suggest removing the Pro Publica statements. If others object, I think moving them to a controversies section along with information describing the medical literature on NSAID toxicity and the FDAs concerns would be a reasonable second choice. Formerly 98 (talk) 05:40, 13 January 2014 (UTC)

 Done Jytdog (talk) 01:31, 24 February 2014 (UTC)

New evidence of acetaminophen toxicity

A new study shows that pre-natal exposure to acetaminophen increases the risk of developing attention deficit hyperactivity disorder (ADHD) - http://www.reuters.com/article/2014/02/25/us-prenatal-acetaminophen-idUSBREA1O1UO20140225 — Preceding unsigned comment added by 46.21.99.29 (talk) 22:09, 25 February 2014 (UTC)

"fetal brain development" section (oy)

• so User:User931 added the following in this dif with edit note "Adverse effects: New study":

Fetal brain development

A recent study published February 24, 2014, studied 64322 live-born children and concluded that Paracetamol use during pregnancy increased the risk of having a child with attention-deficit/hyperactivity disorder (ADHD) and that the risk increased with increased exposure of Paracetamol.(ref)http://archpedi.jamanetwork.com/article.aspx?articleid=1833486(/ref)

• I reverted in this dif with edit note "revert addition of fetal brain defects. we do not base health related content on primary sources. please bring to talk as per WP:BRD

• so User:User931, failing to heed WP:BRD, de-reverted in this dif with edit note "Why are you deleting this? This is a big study published in one of the top scientific journals"

• I re-reverted in this dif with edit note "as per my last note. DO NOT EDIT WAR, as per WP:BRD please bring to Talk and I will answer.

• I will cut to the chase and just answer. The answer is in our sourcing guidelines for health related information, called WP:MEDRS, which I will quote from: "Scientific findings are often touted in the popular press as soon as the original, primary research report is released, and before the scientific community has had an opportunity to analyze the new results. For a short time afterwards, the findings will be so new that they will not be reflected in any review articles or other secondary sources. If the findings involve phase I or phase II clinical trials, small studies, studies that did not directly measure clinically important results, laboratory work with animal models, or isolated cells or tissue, then these findings are probably only indirectly relevant to understanding human health; in these cases, they should be entirely omitted." This is an epidemiological study. Putting this in its own section, with a wildly exaggerated title of "fetal brain defects" violates the letter and spirit of MEDRS, which states that "Wikipedia's articles, while not intended to provide medical advice, are nonetheless an important and widely used source of health information.[1] Therefore, it is vital that the biomedical information in all types of articles be based on reliable, third-party, published sources and accurately reflect current medical knowledge." Results of a single epidemiological study do not constitute "medical knowledge." The very title of an editorial published in the same issue, about this study, says it very clearly: "Antenatal Acetaminophen Use and Attention-Deficit/Hyperactivity Disorder: An Interesting Observed Association But Too Early to Infer Causality." (http://archpedi.jamanetwork.com/article.aspx?articleid=1833483). The purpose of putting such an editorial, with exactly this sort of title, is to prevent the kind of action that User:User931 engaged in here - namely treating this like it is medical knowledge. Jytdog (talk) 03:54, 26 February 2014 (UTC)

That is why I started the sentence with the very recent date of this study, which is published by a third party (the journal). That way everyone understands that this topic will be studied further in the time to come. To me it sounds like you have some biased interest in Paracetamol? A much better alternative than do delete my contribution would be to also add the article you refer to. user931 17:18, 26 February 2014 (UTC)

Oh, please with the accusations of industry shilling for a generic drug that sells for pennies a pill. Please review WP:GF and WP:MEDRS and then come back to discuss this issue. And even if this was MEDRS compliant, don't you think "Fetal Brain Development" was a little over the top as a section head? Brings to mind anecephaly, not ADHD. Formerly 98 (talk) 17:25, 26 February 2014 (UTC)

User:user931 i think you are pretty new here. One of the bedrock principles in Wikipedia is that editors assume good faith about one another - please see WP:AGF. When there is a disagreement, new editors far too often jump to assumptions of bad faith instead of actually engaging with the relevant policies and guidelines under discussion. This is a very bad road to go down and will get you blocked or banned if you persist. You will choose your own road, of course. In any case I will not respond further until you strike your accusation, which you can do by inserting < s > before it and < / s > after it (removing the spaces). Thanks.Jytdog (talk) 18:12, 26 February 2014 (UTC)

Everybody, please keep in mind Wikipedia's Wikipedia:Civility policy. I think Jydog's removal was appropriate, and he or she went above and beyond in explaining the removal with a summary of the relevance of MEDRS in this case. User931 is not a new user, although his/her work on Isotretinoin#Depression, Isotretinoin#Rodent studies and Isotretinoin#Stunted growth was also removed on the basis of WP:MEDRS; in that case his/her reversion of removals seems to have outlasted the interest of the article's other editors. User931, a 2013 study had nearly as many subjects, but that doesn't justify, by itself, including it as a primary source. If you read Wikipedia's guidelines on medical sources, and still feel this warrants an exception, you should explain the rationale in relation to Wikipedia's guidelines. Agyle (talk) 01:35, 27 February 2014 (UTC)

Pregnancy

There were references to pregnancy in the section “other factors” which didn’t seem to flow, so they were deleted and added to newly created “pregnancy” section. Included above mentioned deleted content (except for the content about undescended testicles because it was not referenced). I also included mention of Jmh649’s deleted comments regarding pregnancy and asthma and also brief mention of the information introduced by user931 in the deleted section “fetal brain development” which was also mentioned by 46.21.99.29 in talk:paracetamol “new evidence of paracetamol toxicity” section. Additional references were added. --BoboMeowCat (talk) 06:11, 27 February 2014 (UTC)

Please remember to use secondary sources and format with cite journal not cite PMID. Doc James (talk · contribs · email) (if I write on your page reply on mine) 06:12, 27 February 2014 (UTC)

I reviewed the section on sources. Doesn't say primary sources are not allowed, but rather that article should not be based on primary sources. One line of text mentioning findings of multiple primary sources is not basing article on primary sources or example of undue weight. I agree with the comments by user931 in talk:paracetamol "fetal brain development" section (oy). It seems concerning that this information is being censored/deleted.

From Wikipedia:Identifying reliable sources (medicine) :

"edits that rely on primary sources should only describe the conclusions of the source, and should describe these findings clearly so the edit can be checked by editors with no specialist knowledge. In particular, this description should follow closely the interpretation of the data given by the authors, or by other reliable secondary sources. Primary sources should not be cited in support of a conclusion that is not clearly made by the authors or by reliable secondary sources, as defined above (see: Wikipedia:No original research)."

Also, please note my edit was not simply based on the one new study being currently touted in the press, but also on an older sibling controlled study.

Additionally, could you please explain issue with citing PMID references. They get filled in automatically. What reference format is it that you prefer and why?--BoboMeowCat (talk) 06:49, 27 February 2014 (UTC)

Bobo - Please please listen. We want to provide reliable information to readers. In the biomedical space, the primary literature is notoriously unreliable and variable. We rely on expert opinion to summarize and make sense of the primary literature. That is why MEDRS - as does the foundational policy RS - emphasizes that we create wikipedia content based on secondary sources. When it comes to actual treatments, the secondary literature itself can become a thicket; we therefore rely on the statements of major medical and scientific bodies to guide us. This is all explained at length in MEDRS. Using primary sources like you are doing really violates the spirit of Wikipedia's sourcing and NPOV and OR policies - you are conducting OR by selecting the primary sources that fits your goal. Please use the best and most recent source available. If it is a health-related concept and you cannot find it in the best and most recent sources available it should probably not be in wikipedia. Jytdog (talk) 08:19, 27 February 2014 (UTC)

And please strike your accusation of bad faith editing. You are about a hair from being brought to a board for disruptive editing. You are driving over that cliff. Jytdog (talk) 08:19, 27 February 2014 (UTC)

The first sentence in Wikipedia's Pregnancy section picked two statements from the cite's abstract that discuss only experimental animal studies and human cohort studies that found no association with congenital malformations, ignoring case-controlled studies mentioned in the same paragraph that did find associations, as well as associations with other adverse outcomes discussed in the same paragraph. I think the overall conclusion(s) should be conveyed ("...studies taken together support the conclusion that therapeutic use of acetaminophen does not increase the risk of adverse pregnancy outcome..."), without getting into which types of studies said what about which adverse outcomes (other than perhaps to clarify "adverse pregnancy outcome"). Or if you really want to focus on just one congenital malformations, at least provide broader coverage summarizing the findings of the review. Agyle (talk) 09:09, 27 February 2014 (UTC)

I am OK with simplifying it. To deal with your objection... the abstract mentions 3 case controlled studies with regard to gastroschisis- 2 found nothing and 1 did but it was flawed. hence their conclusion that "The use of single-ingredient acetaminophen during pregnancy can be justified based on outcome data." but like i said I am ok with simplifying it. Jytdog (talk) 12:40, 27 February 2014 (UTC)