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Talk:Paracetamol - Wikipedia, the free encyclopedia

Talk:Paracetamol

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This is the talk page for discussing improvements to the Paracetamol article.
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[edit] Synthesis

"In the laboratory, paracetamol may be easily synthesised by the reaction of 4-hydroxybenzoic acid and ethanamine." This cannot be so! The reaction between an aromatic acid and an amine does give an amide, but not this one! So I changed it.

[edit] Mechanism

Can I point out that this gives too much emphasis to the incorrect COX-3 hypothesis, and that the analgesic effect has been shown by Ottani A et al 2006 to be solely due to its pro-drug effect on the CB1 receptor, and that concentrations required to inhibit COX-1 would be far higher than the theraputic dosage. Also, does anyone know the chemical structure of N-arachidonoylphenolamine, the active form?


[edit] No Side-effects and Age.

I believe that one should mention side-effects (as opposed to toxicity), even if one had the courage to say "no-one has ever had side-effects from this drug" - which is anyway the deduction a reader may make from this article. Patients taking paracetamol can complain of abdominal pain, and of sleepiness, but these have not been linked to paracetamol as such. One wonders whether people really bother to look for these - the drug is sort of "as everyone knows" safe? I recently (past year at least) read a review saying that the recommended dose for paracetamol in the aged (80-95 years) is now 3g/24h. As I recall it had to do with unexpectedly rapid decline in renal function or increase in liver enzymes at 4g/24h, but I cannot find the reference now. Has anyone else seen it? --Seejyb 23:17, 9 August 2006 (UTC)

[edit] Merge proposal with Paracetamol poisoning

Anon editor made good observation on the Paracetamol poisoning article (I've copied across the observation and adjusted tags onto both articles):

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

The Paracetamol poisoning does indeed seem to be a poor duplication of what is currently on Paracetamol. The options are I think:

  1. Delete Paracetamol poisoning, moving across anything that needs be retained or
  2. Split Toxicology off from Paracetamol to replace/improve on Paracetamol poisoning; leaving just short paragraph or two with a linking tag of: {{main|Paracetamol poisoning}} David Ruben Talk 14:53, 19 August 2006 (UTC)
  • Agree with merger of paracetamol poisoning into paracetamol article. On the other hand, paracetamol poisoning is a distinct enough entity in and of itself that a separate article could probably be stand on its own as well. Andrew73 14:47, 19 August 2006 (UTC)
  • Paracetamol poisoning ought to be merged, as that is the main encyclopedic subject. Paracetamol is not currently bloated or unwieldy. —Centrx→talk • 17:29, 21 August 2006 (UTC)

I've merged the articles. As stated above, there didn't appear to be many differences between the two articles. --Uthbrian (talk) 07:47, 28 August 2006 (UTC)

[edit] Panadol availability in the US

The article notes the locations in which various brands are sold; Panadol, while sometimes difficult to find, is available in the US. In cities with sizeable Hispanic populations (at least as far north as Indiana), certain stores (notably Walgreens and Wal-Mart) carry Panadol, presumably because of its popularity in Latin America. I'm not sure if I should add the US to Panadol's availability list, since its popularity is considerably less than Tylenol. Suggestions? Perhaps add the US to the list and note that availability is limited? Student Driver 20:15, 2 September 2006 (UTC)

[edit] Brand names

is the "brand name" section that has just been added really necessary? If i recall, the drug is available generically worldwide, so there is little to no point putting a list of the possible brands, and just adds more confusion to an allready long article. I'm reverting back to the old version for the moment.

[edit] PT/INR and paracetamol

There is a know interaction between tylenol and PT/INR blood clotting times. It is no where near the level of NSAIDs but persons on warfarin therapy should not read the article and believe it is safe to take tylenol as it can increase clotting times substantially. I changed to articles to reflect this. Comment? --Tbeatty 05:02, 21 September 2006 (UTC)

This is only true when using paracetamol in large doses over an extended period of time. I have never heard of a clinically relevant effect when using normal doses. Do you have any references for this? --WS 07:47, 21 September 2006 (UTC)
Usually its a max of 2 extra strength tylenol (500mg) per day, and a max of 8 per week, unless the patient is taking a medication containing apap daily, in that case dosing of the warfarin will be adjusted. --eLeigh33 00:39, 4 April 2007 (UTC)

[edit] Paracetomol in cats and dogs

Although paracetomol is highly toxic in cats as stated, it can be and is used safely in dogs at the correct dose of 10mg/kg twice daily, in fact there is a paracetomol product (Pardale-V[1]) which has a product licence for use in dogs and has been on the market for decades. This section of the article as it stands is misleading and has led to unnecessary worry on the part of dog owners as it contradicts veterinary advice. I propose to edit the paragraph accordingly.--Vetedit1982 22:05, 6 October 2006 (UTC)

[edit] Naming Conventions

I have noticed some confusion among pharmacy patients about the information available on the internet concerning paracetamol/acetaminophen. It is usually due to the, often undefined, interchangable use of the two names. I would like to encourage the use of the abbrevation APAP (which is does not have a second version) when referring to the drug when the other names are not defined on the page. Thank You. --Matt 161.45.236.217 17:54, 2 November 2006 (UTC)

There are policies on the wikipedia defining the naming of the articles. For drugs the naming is in general the INN name (which is in this case paracetamol, hence the article is on this page). If you think there are things to clarify, then I would recommend that a section about the naming is added, with an explanation aimed at resolving the confusion. APAP can be created as a redirect to the INN name of paracetamol, in general it is discouraged to use the abbreviation as the main name of the article, since there may be other uses for the acronym. I hope this clarifies. --Dirk Beetstra T C 22:11, 2 November 2006 (UTC)
I understand that the use of names is usually standardized on Wikipedia, which has been fairly good about providing information to paitents. (Although the whole truth sometimes causes some fear, but that is expected and easily dealt with.) I really was suggesting the use in all cases on the internet, not just here. I just want to make sure that paitents don't get the naming conventions confused with another drug. We had a woman recently who had some liver damage because she read that her medicine contained Paracetamol, so she reasoned that she could take here usual tylenol for her pain (4tabs) She was lucky. Personally, I think that we should only use one name, and I don't care which one, but I'm not in the position to change anything.Matt 161.45.237.73 15:45, 20 November 2006 (UTC)
The problem is that we are not in a position to use more than one name for a given drug. While we try to set up redirects as far as this is possible, the article has to be stored at a single place on the servers. Equally, Wikipedia does not give medical advice: we summarize published material on certain compounds which happen to be used as drugs, which is rather different. A change in the article name would make this information harder to find for many users. Physchim62 (talk) 17:42, 20 November 2006 (UTC)
I disagree with using the name "paracetamol" without "acetaminophen" simply because acetaminophen is almost never called paracetamol in the United States although it apparently is in the UK. We are writing an encyclopedia for the masses, so restricting ourselves to just standard INN names is really an ivory tower kind of exercise that only a chemist might appreciate. I therefore propose that the title be changed to "paracetamol or acetaminophen" —The preceding unsigned comment was added by Woodcore (talk • contribs) 14:00, 9 January 2007 (UTC).
For a comparison, see Gasoline and Talk:Gasoline, where a consensus was reached to title the article "Gasoline" and to stick to that word in the article text, except in the introduction. Paracetamol presents a more difficult problem because speakers of different varieties of English usually are not familiar with both forms (whereas most people probably know both gasoline and petrol), but I think the principle holds. Sticking with one form also makes the article more readable. As long as there are appropriate redirects/links (as there are here from Acetaminophen and APAP), and all well-known names are covered in the introduction, I think that sticking with a single term for the bulk of the article makes it markedly better. There is more info at WP:Naming. I also want to clarify some points about my Gasoline example: (1) the point is not that the US term should be preferred; (2) one point is that the article should have a single name, and forms like Gasoline or petrol and Petrol (Gasoline) are strongly discouraged; (3) the other point is that the article title is decided by consensus, usually right here on the talk page. I have also raised this issue from the perspective I've just outlined in a topic below. --Tkynerd 15:44, 9 January 2007 (UTC)

[edit] U.S. recall of generic paracetamol

I have moved the note added by Zandperl (talk · contribs) to the top of the article into a separate section. IMHO this is a notable incident which merits inclusion in the article, although I am unsure as to the future permanence of this section — perhaps a "Notable incidents" section could be created, with a short note on the 1982 Chicago Tylenol murders as well. Comments and criticism are more than welcome. Fvasconcellos 14:05, 14 November 2006 (UTC)

Recalls like this are not really the stuff of Wikipedia until after the event: we are supposed to be an encyclopedia and not a news service. Physchim62 (talk) 15:25, 14 November 2006 (UTC)
I agree; I, however, chose to keep the information because a) I am wary of removing others' contributions when they are made in good faith and are neither damaging nor misleading, and b) it's a fair assumption that people (particularly in the U.S.) may be turning to Wikipedia for information regarding this incident. Maybe it should indeed be removed, and re-added later if it's still worth it? Fvasconcellos 16:17, 14 November 2006 (UTC)
Thanks for the note Fvasconcellos.
I'm the one who put it in. My reasoning was threefold: (1) we do sometimes document current events (for example, US hurricanes), (2) people may turn to Wikipedia for information about this event, and (3) it's a piece of information that could help our users. If Wikinews appeared to have an article, perhaps a link to it would be most appropriate, but I couldn't find one. My opinion is that for now it seems appropriate to at least leave the information somewhere in the article. It can be removed with time when it is less relevant. --zandperl 21:05, 14 November 2006 (UTC)
Update: I am removing the section. Nearly two months have elapsed, and there seem to have been no notable consequences; I therefore think the section is in fact not notable enough to remain in the article. If anyone objects, it will still be in page history for future reference. Fvasconcellos 13:56, 3 January 2007 (UTC)

[edit] Paracetamol in Australia

Just pointing out that Paracetamol in australia is commonly known as 'Panadol' rather than 'Herron'. Should I change the intro? --Gunny01 05:19, 1 December 2006 (UTC)

The list of trade names should probably be sorted into alphabetical order. Herron is still a trade name for Paracetamol in Australia [2] (although we may possibly be spam victims given the promenance of the name). Physchim62 (talk) 17:43, 1 December 2006 (UTC)
I fail to see, on evidence of http://www.herron.com.au/products/analgesics/analgesics.html that Herron is specifically a trade or brand name for Paracetamol. As the link clearly shows, Herron seems to be used as a trading name for the company, i.e. name of a product range which includes paracetamol and ibuprofen, hence "Herron Paracetamol" and "Herron Blue Ibuprofen". Compare to their laxative products http://www.herron.com.au/products/laxatives/laxatives.html for which "Sennetabs" and "SenneSoft" are brand names. Hence is not Herron merely just a generic paracetamol manufacturer and so inappropriate to list in the introduction's collection of branded products ? Conversely the US Tylenol or UK Panadol ranges all contain paracetamol. However, not living in Australia, I am not aware how notable Herron is in terms of market share, primacy by dates of marketing in Australia, or of the common usage of the term "Herron" (maybe is is perceived by the Australian public as a synonym, eg as "Kleenex" is for tissues or "Hoover" for vacuum cleaner). David Ruben Talk 02:38, 10 December 2006 (UTC)
I've removed Herron as a brand name in Australia and added Australia to the Tylenol list. Herron is a manufacturer of many products, one of which is "Herron Paracetamol" (Mollwollfumble 01:45, 13 December 2006 (UTC))
Problem is no one in Australia calls it Tylenol. Ask for Tylenol in Australia and you'll get a strange look. Panadol is the common name for Paracetamol. In australia, Panadol is to Paracetamol as Hoover is to vacuum cleaner, etc etc. It's a generic name. Gunny01 22:55, 14 December 2006 (UTC)


"In Australia, the limits appear to be 24 and 100 tablets respectively." This information ought to be verified, or if it cannot be, removed. "appear to be" implies uncertainty and unverifiability. To quote the warning directly below this editing box, "Encyclopedic content must be attributable to a reliable source. " Glacialfury 23:19, 3 April 2007 (UTC)

24 is definate, 100 i've never seen a bigger pack, but who has that much pain

i swapped 24 and 100 round. even if it's not properly verified, it made no sense the other way around Snappyfool 10:21, 4 May 2007 (UTC)

[edit] Two issues about this article

(1) Given that Wikipedia standards require that the INN name (here, paracetamol) be used as the name of the article, shouldn't that name also be used consistently throughout the article? Some passages use the name acetaminophen. I could be bold and fix this, but this is my first trip to this article, and I'd prefer to see if there is any consensus on this first.

Go ahead. The name acetaminophen is defined in the first sentence, as guidelines require, but in the text of the article we should only use paracetamol. Physchim62 (talk) 16:06, 9 January 2007 (UTC)
Done. I only changed it in a few places where it seemed appropriate; there are one or two places in the article body where it seemed appropriate to leave "acetaminophen." I also had to be careful not to change the titles of any of the referenced articles! :-) --Tkynerd 18:26, 9 January 2007 (UTC)

(2) I find the following passage confusing: However, there are important differences between the effects of aspirin and those of paracetamol. Prostaglandins participate in the inflammatory response which is why it has been known to trigger symptoms in asthmatics, but paracetamol has no appreciable anti-inflammatory action and hence does not have this side-effect. What, exactly, is it that "has been known to trigger symptoms in asthmatics"? I suspect aspirin is what is referred to, but I don't know for sure; in any case, the passage as it stands is difficult to understand. --Tkynerd 00:46, 9 January 2007 (UTC)

The whole section needs rewriting, with a little less speculation. Physchim62 (talk) 16:06, 9 January 2007 (UTC)
That's not me. I'm no scientist. :-) I would like to see it clarified, though. --Tkynerd 18:26, 9 January 2007 (UTC)

[edit] Considered safe

I modified the word "safe" to "considered safe." (The actual phrase conventionally used is "generally considered as safe.") Geoffrey.landis 14:50, 24 January 2007 (UTC)

[edit] Proposal

How do people feel about taking the Metabolism paragraph and moving it above Mechanism of Action since then it would be easier to merge Mechanism... with Comparison with NSAIDS -- those two sections repeat each other quit a bit, and the possibility of liver toxicity I would think should be added in the Comparison... paragraph (just as a sentence, as the Toxicity section otherwise gets into liver metabolism, but a good comparison with nsaids... maybe take the sentence from further down about nsaids being recommended over apap for hangovers). If Physchim62 or others could list some of the stuff that sounds too speculation on Talk then we could root those out while merging/clarifying those paragraphs. Gaviidae 18:49, 29 January 2007 (UTC)

[edit] Narrow therapeutic index?

This diff shows where I reverted edits by an anon asserting that paracetamol actually does not have a narrow therapeutic index. I find it difficult to believe this is true, considering the review process this article has been through, but I wanted to bring up the issue here for discussion. (Leaving aside the fact that the anon took it upon himself to E-mail me -- not through Wikipedia, either -- to take issue with my revert. Also, the anonymous edits were unsourced, which was the main reason I chose to revert them.) I would recommend that someone explain here in detail exactly WHY paracetamol is said to have a narrow therapeutic index. Thanks. --Tkynerd 23:48, 30 January 2007 (UTC)

The therapeutic index is defined as the TD50/LD50. This means that the dose required to reach a toxic level in 50% of subjects divided by the dose that is effective in 50% of subjects. For obvious reasons these kinds of tests are most commonly done on rats. The closer this number approaches 1 the more narrow the therapeutic index occurs. If the therapeutic index is 1 then the drug will become toxic at the same dose that it becomes effective at. The FDA web site defines having a narrow therapeutic index as having a therapeutic index of less than 2-you may go there and search therapeutic index to verify this information(http://www.fda.gov/cder/news/ntiletter.htm). That is, the toxic dose is less than 2 times the therapeutic dose. Also, the FDA website lists acetaminophen as a "safe and effective drug" (http://www.fda.gov/fdac/features/2003/103_pain.html). With some simple math it becomes obvious that acetaminophen does not have a narrow therapeutic index. In the wikipedia article the toxic dose is suggested to be 10g or 150mg/kg body weight. It also says that if taken chronically at 4g/day toxicity could occur. Given that we know that the effective dose is about two tylenol tablets-for headaches (1000mg or 1g) and the effective dose for more severe pain is about two perscription tablets (1600mg or 1.6g) we can now divide the suggested toxic dose by the effective dose. Even at best, (4/1.6) we still do not get a ratio of less than 2, so acetaminophen does not have a narrow therapeutic index. By the way, the recommended does of acetominophen suggests not going over 4g in 24 hours on the side of every bottle, which could be considered overdoseing. The FDA also recommends not overdosing or liver damage could occur. The fact that liver damage could occur at less than 4g a day is a side effect of the drug and does not cause the therapeutic index to shrink-every drug has a side effect. The fact is that in the wikipedia article the therapeutic index is called "narrow" under the toxicity heading, which implies that it is dangerous because the effective dose is very close to the toxic dose. The truth of the matter is that acetaminophen is a very safe drug. If the therapeutic index was narrow it would be not be perscribed to pregnant women, children, elderly, or anyone for that matter who didn't seriously need it. Citation 9 in the article discuss the overdoes problems not that the therapeutic index is narrow, and the fact that the UK and Ireland don't sell it over the counter doesn't mean that the therapeutic index is narrow either. For example, antibiotics in the US don't necessarily have a narrow therapeutic index, but perscriptions are still needed to obtain them. This portion of the article makes acetaminophen sound like a deadly drug and is very misleading, especially because it doesn't have a narrow therapeutic index. It should be altered.--William mcfadden 05:12, 31 January 2007 (UTC)
It doesn't have a narrow therapeutic index. —Preceding unsigned comment added by 67.166.96.147 (talk • contribs)
Maybe for prescription medication, the therapeutic index must be lower than 2 to be considered narrow, but for OTC medications, or worse yet, medications which anyone can buy off the shelf at any corner store, the therapeutic index should be significantly higher than 2 to be considered safe. For decades Tylenol has been pandering acetaminophen as much more safe than any other painkiller and doctor recommended. Recent studies prove otherwise. BTW, liver damage is a very serious "side effect". I hope you're not trying to compare liver damage to side effects like nausea, dry mouth, constipation or drowsiness! --Thoric 16:08, 31 January 2007 (UTC)
Side effects
I am merely trying to distunguish between what a side effect and toxic effect of a drug are. A generic definition could be that side effects occur at any concentration of the drug, but a toxic side effect only comes into play when too much of a drug is given. The side effects of a drug don't effect the therapeutic index because they are present at therapeutic dosing levels. Liver damage can occur with overdosing when the metabolic products of acetaminophen overcome the systems ability to handle them; but to reach the level needed to produce toxicity, there would need to be a lot taken. Perscription drugs only give a higher dose of the drug, which doesn't change the fact that toxic side effects are seen only on overdose or large doses. The perscription drugs, because they are given in a higher dose, are much easier to overdose on. BTW, the therapeutic index for acetaminophen is much larger than 2. In fact, it is much higher. I merely used 4g in the calculation above because the article states that 4g/day is the lowest dose that could cause toxic side effects in chronic users. The article states that the narrow therapeutic index is causing overdosing and toxic problems. That isn't true. The commonality of the drug makes it easy to overdose on without knowing it. Without a doubt all drugs that have a narrow therapeutic index will be perscription, but even drugs that have a broad therapeutic index can be perscription, mostly because they are given in high doses-like acetaminophen. Common overdosing of acetominophen is caused by naive suicide attempts or because a person is taking too many medications that contain acetaminophen. Given that the drug is commonly used in a lot of medications it is easy to overdose on; however, the therapeutic index is still the same-wide. It still takes a lot of acetaminophen to become toxic, much more than a therapeutic dose, which means that the therapeutic index isn't narrow. The recent articles on acetaminophen are describing what can happen when overdose occurs. It is fairly recent knowledge that acetaminophen can cause liver damage, but the key word here is "overdose". The articles aren't saying that acetaminophen is dangerous at therapeutic doses-quiet the contrary. It is a vary safe drug at therapeutic doses, but as soon as you reach a toxic level it isn't so safe anymore. Fortunately we know that acetaminophen has a therapeutic index that is fairly large. This still means that the therapeutic index is not narrow. Even if extremely low doses were associated with liver damage, it would be considered a side effect and not a toxic effect, which means it wouldn't affect the therapeutic index. Side effects can be anything that a drug causes at therapeutic levels-including serious side effects. The article should say that the therapeutic index is large, but the commonality of the drug make it easy to overdose on; this can lead to liver damage.--William mcfadden 19:40, 31 January 2007 (UTC)

I have edited out the portion that says that paracetamol has a narrow therapeutic index. The original article had no reference for this claim. The article that was sighted shortly after looks at the potential for overdose and does not indicate that the drug has a narrow therapeutic index. The article was never used to as a citation that said that paracetamol has a narrow therapeutic index anyway. I have not listed a citation because I added no claim to the article and did not say that it has a wide therapeutic index. However, it has become clear, from the above, that it doesn't have a narrow therapeutic index and this should not be in the article. It would be nice if someone would look up a citation for this.--William mcfadden 21:11, 5 February 2007 (UTC)

It's not at all "clear from the above" that paracetamol does not have a narrow therapeutic index. There is no consensus on this point. I'm reluctant to revert your edit, although I'm tempted to do so, but you should do so yourself, since the edit concerns a controversial point on which there is no consensus yet. --Tkynerd 21:58, 5 February 2007 (UTC)

I have taken out the controversy. I have not claimed that paracetamol has a wide or a narrow therapeutic index in my edit. The previous article claimed a narrow therapeutic index with no citation. If it is in fact a controversial point in your eyes then no claim should made, and I have changed the article to reflect that. If Tyknerd is right about the controversy, reverting my edit would be staking a claim in an un-source claim that is controversial. Recent articles claim new evidence of toxcity based on the wide availability of paracetamol; they in no way claim a narrow therapeutic index. Even if side-effects are discovered, a side-effect doesn't change the therapeutic index at all! Again, if you have had background in pharmacology, then it would be very clear from the above that paracetamol does not have a narrow therapeutic index. I would refer you to the FDA pages as a reference. Just as a side note, Harvard recently produced a new textbook for medical students on pharmacology. If this book is not consensus, I don't know what is. It says that acetaminophen is very safe, but the common nature of it makes it easy to overdose on. It is not a controversial point. I leave the reference out because most people don't have the physiology background to just start reading this book, but to satisfy the needs of anyone who thinks it is controversial, I have made no claim.--William mcfadden 22:25, 5 February 2007 (UTC)

You didn't take out the controversy; you took out what YOU thought was controversial. It was explained above that the ratio below which a drug's therapeutic index is called "narrow" is much higher for OTC drugs. Your response ("Perscription drugs only give a higher dose of the drug") applies only to different dosage levels of the same drug, not to different drugs. Again, you need to revert your removal of this information until consensus is reached. --Tkynerd 23:48, 5 February 2007 (UTC)

Okay, first of all, the therapeutic index DOESN'T CHANGE whether the paracetamol is given OTC or by perscription. However, the potential for toxic overdose is much higher with higher dosages being taken. I think where you are making an error is that if you get paracetamol in Tylenol or if you get it in a straight perscription form it is still exactly the same! The name of the brand doesn't change the drugs chemical structure, so we want the information to apply to different dosing levels not different drugs (it is all the same chemical structure). You would know this if you had a background in pharmacology. Tkynerd claimed "I am no scientist" in the above comments. It makes it clear that you have no idea what you are talking about when it comes to pharmacology. If you want to stake a claim that a narrow therapeutic exists please source your information, and there still has not been a citation for paracetamol having narrow therapeutic index. The only controversy is that you think it is controversial, and you don't have a source or a leg to stand on. Secondly, I have made not claim in the article, and until you can get some sources claiming a narrow therapeutic index you are entering faulty information. You asked for an explaination of a narrow therapeutic index, and no one can give one for paracetamol because it doesn't exist. I have played your little game and still you are unhappy about more accurate edits. You watch this paper like a hawk and you don't allow updates from people more experience than you. It is people like you that keep wikipedia from becoming accurate and prevent me from being able to use it as a viable source in any collegic paper. I feel you have done nothing but belittle me over something you know nothing about. I really don't think you understand therapeutic indeces or have ever studied them, so until you get a PhD, MD, can source something or prove something please stop asking me to revert my edits based on no data.--William mcfadden 05:51, 6 February 2007 (UTC)

References to paracetamol/acetaminophen having a low/narrow therapeutic index: [3] [4] [5] [6] [7] --Thoric 06:13, 6 February 2007 (UTC)

Thoric- these references don't say it has a narrow therapeutic index. I have read all of them, and it only indicates risks of acetaminophen. In fact references 3 says "However, unlike the classical NSAIDs such as aspirin or indomethacin, therapeutic doses of paracetamol do not damage the stomach." Reference 6 says "anti-inflammatory drugs should be given in monotherapy and at the lowest effective dose in order to reduce the risk of serious upper gastrointestinal complications", which is a given because you don't want to reach toxic doses. Do you think that this paper would even suggest giving the drug in non-life threatening situations if it had a narrow therapeutic index? NO. None of these articles stake the claim that there is a narrow therapeutic index they only are speaking about problems that might exist. These references don't claim the therapeutic index is narrow.--William mcfadden 07:12, 6 February 2007 (UTC)

You read all of them? The second one says, and I quote, "It has been suggested that the therapeutic index for paracetamol may be as low as 1.7", and cites references to back up that claim. How about reading those references again? --Thoric 18:20, 6 February 2007 (UTC)

Keep in mind that it says "suggested" and "may be" these in no way establish a narrow therapeutic index. As I have said, these references talk about problems that might exist not those that do exist. The author is in no way saying with absolute certainty that a narrow therapeutic index exists, but it has been suggested. I stand by my previous comments. Additionally, the study is in children not adults and says that reports of liver toxicity from paracetamol are rare. The Google scholar has cited a reference having a narrow therapeutic index in alcholics, but it also says that damage from it can vary. This could indicate a narrow therapeutic index for alcoholics, but I am not convinced that it applies to healthy adults. If so, as cited above, I don't think the FDA would list it as "safe". Again, no claim in the article has been made about therapeutic indeces. If you would like to add a sentence saying that paracetamol has been suggested as having a narrow therapeutic index in children and alcoholics, but the FDA lists it as a safe and effective drug at therapeutic levels, by all means do so.--William mcfadden 18:50, 6 February 2007 (UTC)

[edit] Google Scholar shows

One swallow does not a summer make and this is a published letter in a reputable journal, not a refereed paper. Still, seems like there's enough support to note the claim, perhaps with qualificationn. The clear point of the letter seems to be that doctors shouldn't perscribe paracetamol to alcoholics. David.Throop 14:23, 6 February 2007 (UTC)

[edit] Obsolete?

User:The Right Honourable has just removed the British Approved Name, the INN and the USAN from the infobox, describing them in an edit summary as "obsalete" [sic]. Is there any basis for this? In what sense are they obsolete? --Tkynerd 04:43, 10 February 2007 (UTC)

I believe he is referring to this discussion, which hasn't gone too far. Fvasconcellos 14:25, 10 February 2007 (UTC)
OK. Then "obsolete" isn't really the right term; maybe "premature" would have been more appropriate? :-) In any case, I assume the template will be sorted out in due time, and with it the version carried by this article. Thanks. --Tkynerd 14:31, 10 February 2007 (UTC)

[edit] Synthesis

As this is an article on a chemical, shouldn't it include one or more total synthesis of the compound as is customary on other articles on chemicals? There should also be descriptions of industrial synthetic pathways. Loom91 06:00, 21 February 2007 (UTC)


This article http://www.chemsoc.org/pdf/LearnNet/rsc/paracetamol.pdf from the Royal Society of Chemistry explains the process of making it in the lab, nothing really about manufacture in industry, I would write it up, but I really don't quite feel qualified enough since I'm just a first year 6th form student. I may do my best at some point, but no promises.

mbree 08/07/2007 16:11

[edit] Acetaminophen

Does amoxicillin have a reaction with acetaminophen? --myselfalso 00:28, 22 February 2007 (UTC)

Not at all! Hope that answers your question. 82.32.203.68 11:04, 19 March 2007 (UTC)

[edit] Passing through system

How long does it take for acetaminophen to pass through one's system? If one were to take four capsules during the day, and then hours later at night decide to have a few drinks, is there still a risk factor for toxicity? Altamer 02:15, 4 March 2007 (UTC)

it's half life is 1-4 hours so i doubt a few drinks would hurt you.


toxicity only occurs above 4 grams, that's 8x 500mg pills. with stomach problems try to avoid paracetamol, it won't help! if your already taking 4 per day you should really be going to a doctor Markthemac 00:14, 17 June 2007 (UTC)

[edit] name differance

could we have a page for names of pharms which have different names in UK and US —The preceding unsigned comment was added by The Right Honourable (talk • contribs) 07:41, 4 May 2007 (UTC).

[edit] The History of paracetamol

I think it might be interesting for the article to discuss the work of professor Kussmaul in 1880 using acetanilide, not paracetamol, which led to the discovery of it's antipyretic properties - which then led on to the discovery of dirivitives which include paracetamol.

I say this just because the story is interesting and would be beneficial to the article.

I source my information from the Royal Society of Chemistry student document on Paracetamol, which can be found here: http://www.chemsoc.org/pdf/LearnNet/rsc/paracetamol.pdf

It states:

At the University of Strassburg in the 1880s Professor Kussmaul, of the Department of Internal Medicine, asked two assistants to give naphthalene as a treatment for intestinal worms. The medicine had little effect on worms, but one patient had a great reduction in fever temperature. It was found that this patient had, in fact, been given acetanilide instead of naphthalene due to a mistake at the pharmacy!

If you read further, it explains the need for a better drug to be obtained due to it's bad side effects, this was the basis of the necessity for paracetamol to be discovered, and in this way it is quite relevant to the article.

mbree, 07/June 07

[edit] Overdose prevalence

User:Assassin3577 added:

However, overdosing on paracetamol is extremely difficult owing to it's extremely disgusting taste, and therefore by ingesting too much, the body will simply reject the dosage and expel the analgesic via emesis

Without citation, this seems unlikely: compare "Acetaminophen overdose is one of the mose common poisonings worldwide" [[8]] and "Now, a new study shows a rise in cases of acute (sudden) liver failure reportedly linked to Tylenol overdoses." [[9]].

[edit] Mention methionine treatment for overdose?

As mentioned in T G Mant; J H Tempowski; G N Volans; and J C Talbot (1984). "Adverse reactions to acetylcysteine and effects of overdose.". Br Med J (Clin Res Ed) 298: 217–219. , menthionine used to be very popular, and is cheaper than n-Acetylcysteine. Antidotes for Poisoning by Paracetamol also talks about it, and it's quite effective within 8 hours or so. These are all from the 80s, and I'm not sure what current fashion is. Here's a paper from 2003: Oral methionine compared with intravenous n-acetyl cysteine for paracetamol overdose claiming that acetylcysteine is better. 71.41.210.146 06:45, 10 July 2007 (UTC)

The article has been updated. Dr. Cash 19:50, 17 August 2007 (UTC)

[edit] Of interest?

http://www.dailymail.co.uk/pages/live/articles/health/dietfitness.html?in_article_id=483993&in_page_id=1774&ICO=HEALTH&ICL=TOPART Anyone know where to find the study that the popsci article here is based on? MrZaiustalk 07:02, 28 September 2007 (UTC)

[edit] Redid Mechanism

As has been mentioned before, the mechanism section of this article was pretty bad. It kind of rambled and jumped from point to point, and still talked about the debunked COX-3 hypothesis. I rewrote it from scratch. It's got some good references in their now, some recent reviews and all the important original research articles. To me it seems painfully obvious that paracetamol's anti-pyretic action is via COX modulation, while it's anti-nocicpetive action is via AM404, but I haven't found a paper that puts it like that, so I haven't said it (original research). I could go into more detail about how paracetamols action on COX doesn't quite fit the picture, but I feel this might be a bit above and beyond the scope of this article. Thoughts? Bilz0r 09:14, 4 October 2007 (UTC)


At minimum, this passage

The activity of the COX enzyme relies on its being in the oxidized 
form to be specific, tyrosine 385 must be oxidized to a radical.

needs a period (a.k.a. full stop) after 'form'. However, I would like to reword it. See what you think of this

To metabolize arachidonic acid, an amino acid in the COX enzyme 
must be oxidized.  To be specific, the tyrosine at position 385 
in the COX enzyme must be oxidized into a radical.

[edit] OR?

This paragraph, from "Risk factors", should probably be removed:

Surprisingly, paracetamol can be physically addictive: the needed dose increases with each administration, and there is a distinct withdrawal syndrome, which resembles the headache for which the drug was first taken, but not exactly. This is easily demonstrated, at least in rural France, where this common drug is not sold in bottles of 100 pills but in boxes of 16 blister packs of 500-mg tablets/caplets/capsules. (As in the U.S., it is hard to find 325-mg "regular strength" pills: the 500-mg "extra-strength" pills have become the more usual dose.) If one takes two every six hours until the 16 pills are exhaused, one will discover that, as the time for the next dose approaches, the headache will return, with a slightly different kind of pain and greater intensity. After the 16 are exhausted, the intensity is severe enough to be mistaken for a migraine. (This is of little concern to those who have easy access to emergency rooms and to pain management specialists (physicians unafraid to treat pain with narcotics and who are trained to distinguish real addicts from people in pain), but these are not easily found on short notice, particularly in rural areas.)[citation needed]

—Fvasconcellos (t·c) 15:30, 4 October 2007 (UTC)

OK, three days have passed and there has been no objection, so I've removed the text. It was uncited, anecdotal, and contained arguably POV statements; at the very least, it didn't fit into the "Risk factors" section. I'll leave it here anyway for convenience, should there be anything worth rewording and adding back in. Fvasconcellos (t·c) 22:36, 7 October 2007 (UTC)

[edit] The seratonin (5HT) system

"Paracetamol reinforces the decending inhibitory pain pathways" A study which also confirmed thats the central 5HT mechanism isn't stimulus dependednt —Preceding unsigned comment added by Blonde2max (talk • contribs) 22:33, 7 November 2007 (UTC)


[edit] Error in one of the external links

This external link: http://www.ch.ic.ac.uk/rzepa/mim/drugs/html/paracet_text.htm, labeled "History & chemistry of paracetamol," contains a major error. It states, "When mixed with codeine, it goes under the tradename Tylenol." This is completely untrue. The only active ingredient in Tylenol is acetaminophen/paracetamol. Prescription-only forms of Tylenol (with numbers following the word Tylenol) contain codeine, but not Tylenol itself. Suggest this external link be removed, especially since I see no way, even on the home page, of contacting that webmaster. Suggest finding a U.S. site to link re: history and chemistry of Tylenol, especially since that UK one is incorrect and the drug was first produced in the U.S. Softlavender (talk) 01:49, 13 December 2007 (UTC)

[edit] Brand Name Table

I added, what I hope is, a complete list of brand names. I forgot to log in when I did this so it posted as anonymous. I just wanted to let the community know who to contact with comments if neccesary. --Remark knights (talk) 18:55, 28 December 2007 (UTC)

[edit] Error in mechanism?

Under the metabolism section, there is a scheme showing the biological fate of paracetamol. After N-hydroxylation, the scheme shows square brackets with a "c" subscript. What does that mean? In addition, the next arrow says "rearrangement", and then shows a product which presumably result from expulsion of hydroxide. As written, that would be an elimination, not a rearrangement. Also, there is an apparent double bond missing to the bottom oxygen, if the mechanism is what I think it is. Finally, the toxic metabolite NAPQI is mentioned in the text, but not labeled. Eugene Kwan (talk) 09:41, 2 January 2008 (UTC)

I agree that there's a problem in the mechanism. The toxic metabolite should have the same structure shown in NAPQI, but it's got an OH group where it should be quinone (double bond to O). Queerwiki (talk) 00:56, 6 May 2008 (UTC) (wrote this comment without logging in and then corrected by logging in)

[edit] References

Please can you provide a reference for the following statement you make:

"It is also used in combination with opioid analgesics to prevent recreational use of the opioid since the high hepatotoxicity (liver damage) means that a person cannot do so without causing serious injury or death." Emsiba (talk) 22:24, 7 April 2008 (UTC)

This article appears to have an overall bias against paracetamol/acetaminophen. I do not know if this is justified by current medical opinion. As for that particular claim, I have removed it because (a) it is not referenced and (b) the following claim (that paracetamol has no effect in combination with opioids) is apparently incorrect, based on a reference I found and added. --Macrakis (talk) 21:05, 11 April 2008 (UTC)


The justification for adding the opiates to combination products is not based on deterring people from abusing opiate drugs. It was intended to enhance the drugs efficacy but there isn't much evidence to support that. I don't think it was trying to portray paracetamol negatively but was meant to show opiates poorly in combination with paracetamol. It's based on clinical evidence that comparing paracetamol to paracetamol + weak low dose opiate (Co-codamol) it has been found that there is marginal analgesic benefit to using co-codamol over paracetamol alone, however the opiate side effects (nausea and constipation) develop. In essence you get no real added pain relief from the opiate but all the side effects.
The reference you've chosen I'm going to have to change because that is to do with post-operative use of paracetamol in decreasing a patient's morphine demand, but states that it is to do with combination products. It's based on evidence found by the French with their use of propacetamol. Medos (talk • contribs) 21:27, 11 April 2008 (UTC)

[edit] Make the article reader friendly by saying that it is about a painkiller

Use a few words to explain in common English that this article is about a painkiller. I see no harm and only advantages in this. Thanks Andries (talk) 21:38, 11 April 2008 (UTC)

See Wikipedia:Explain_jargon which supports my opinion. Andries (talk) 20:49, 12 April 2008 (UTC)

[edit] Toxicity section; UK limits on sales

Present passage:

"In the UK, sales of over-the-counter paracetamol are restricted to packs of 32 tablets in pharmacies, and 16 tablets in non-pharmacy outlets.[33] Up to 100 tablets may be sold in a single transaction, however in pharmacies, 32 may only be sold, with more being sold at a pharmacists discretion."

This reference is bit vague and misleading ; the law has changed a number of times in the meantime, to reflect the prevalence of paracetamol in many otc preparations. For the text, I would propose (not least because the above is slightly misleading):

"Broadly speaking, in the UK sales of paracetamol are restricted to packs containing no more than 16 tablets of up to 500mg (for adult consumption) at non-pharmacy outlets, and packets containing no more than 32 tablets at Pharmacy outlets. Pharmacies may dispense quantities greater than 32 tablets, with a prescription, but the sale of quantities greater than 100 tablets is a criminal offence. However, the quantities applicable to effervescent, powdered, granulated and liquid forms and limits for use in children vary widely. see http://www.rpsgb.org/pdfs/medsparacettable.pdf

THe current reference (33) is the interpretation of the law (as it was in 1997) by one trading standards office; the law has been amended a number of times in the meantime to reflect the prevalence of paracetamol in many OTC preparations. I propose the link: http://www.rpsgb.org/pdfs/medsparacettable.pdf as it is published by the relevant professional body, and is more detailed and up to date.


Myredroom (talk) 17:26, 21 April 2008 (UTC)

[edit] Grammar Minor Error

Was just surfing wikipedia. "lack side effects of aspirin" in the introductory paragraph doesnt sound correct, its as if side-effects are a good thing to have ...i think the word "lack" should be replaced.

thanks 220.253.201.59 (talk) 13:37, 28 May 2008 (UTC) anonymous surfer


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