Talk:Paracetamol/Archive 1

message: What is the evidence that that is widely agreed upon? Kd4ttc 23:09, 11 May 2004 (UTC)
thread_title: General agreement on activated charcoal

message: I'm nominating this article for featured article (see top of this page). Ksheka 22:29, May 8, 2004 (UTC)
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It seems that this article has been copied (with a citation back to the wiki).  I'm flattered! Ksheka 14:36, May 9, 2004 (UTC)
::well done! --e 22:44, 9 May 2004 (UTC)
replies: text: Taken care of. Thanks for the idea. Ksheka 22:00, May 9, 2004 (UTC)
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these are a few musing that could be integrated:
# because of widespread availability it's effectiveness is often underestimated
#* Added to the Overview section. Ksheka 11:52, May 10, 2004 (UTC)
# need to emphasise need for early Px of OD
# ? mention phenomenom of deliberate od --> no effects --> remorse and desire to live ---> fulminant hepatic failure ---> death after a few weeks ???
#* Added to the Natural history section. Ksheka 11:52, May 10, 2004 (UTC)
## There's actually two different scenarios. If someone more elequoent that I would like to write them up, I would be much obligded. :-) Ksheka 01:33, May 10, 2004 (UTC):
##* An individual ingests acetaminophen in a suicide attempt, changes their mind, and then develops hepatic necrosis
##* An individual ingests acetaminophen, not as a suicide attempt, but just as a call for attention.  They choose acetaminophen because they think it's harmless.  Then they develop hepatic necrosis.
# can be taken in combination with NSAIDs providing additive analgesic effects
# ???used to be recomended prophylacticly before childhood immunistations but not any more?? don't know details or why thinking changed... ?alex? --e 22:44, 9 May 2004 (UTC)
thread_title: [[Wikipedia:Featured article candidates | Featured article candidate]]

message: what do people think about splitting the toxicity out of this page into a separate article? I think toxicity is so common and so well covered it is deserving of going solo! Erich 04:35, 14 Jun 2004 (UTC)
thread_title: Splitting the page

message: In http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11113024&dopt=Abstract I read that acetaminophen is counted among the NSAIDs, yet our articles claims otherwise. AxelBoldt 20:00, 21 Oct 2004 (UTC)
replies: text: Some people group paracetamol as an NSAID because of its mechanism of action. However, since paracetamol has no appreciable antiinflammatory effect, it would be inappropriate to classify it as an NSAID. (see NSAID for more details). Techelf 08:06, 4 Nov 2004 (UTC)
thread_title:  NSAID? 

message: I removed the reference to isoniazid and stimulation of cytochrome P450. Isoniazid actually inhibits cytochrome P450 (perhaps there was confusion with rifampicin?). The mechanism of isoniazid-induced hepatotoxicity is not fully understood. Isoniazid is metabolized by N-acetyltranferase. The gene for this enzyme has polymorphisms that cause variation in the enzyme's activity. These different phenotypes are commonly called 'slow acetylators' and 'fast acetylators'. Once the acetylation pathway becomes saturated, metabolism switches to cytochrome P450. Slow acetylators typically have a higher incidence of hepatotoxicity, probably because the cytochrome P450 degradation products are toxic. [Cytochrome P450 inducers, such as barbiturates and rifampicin, lead to increased risk of isoniazid toxicity.] Isoniazid does increase the risk of paracetamol toxicity, but this is probably due to an additive effect of isoniazid degradation products with NABQI. Axl 17:08, 10 Nov 2004 (UTC)
replies: text: Isoniazid is an inducer of CYP2E1 . In any case I've put additional references in the main article concerning interactions. You are right though about the complexity of isoniazid-induced hepatotoxicity; it seems that the hepatotoxicity of the combination with paracetamol may not necessarily relate to CYP2E1 induction. Techelf 07:22, 11 Nov 2004 (UTC)

text: I accept that my claim that isoniazid is an inhibitor of cytochrome P450 is simplistic. Isoniazid inhibits CYP1A2, 2A6, 2C9, 2C19 and 3A (and probably many others). However even your reference is too simplistic. Isoniazid has a complex interaction with CYP2E1, involving first induction, later followed by inhibition.
Axl 12:20, 11 Nov 2004 (UTC)
thread_title:  Isoniazid 

message: "While aspirin acts as a competitive inhibitor of COX..."
I believe aspirin permanently acetylates COX enzymes, rather than inhibiting it by competition with it's natural substrate (the page on aspirin -  - appears to agree)
:It is irreversible, and the main article has been corrected. -Techelf 11:51, 12 May 2005 (UTC)
thread_title:  Aspirin Reference 

message: I was reading through this and was very surprised to see, in a peer-reviewed article, the first sentence of the History section, which began "Prior to the creation of paracetamol, the only antipyretic agent available was cinchona bark..." I'm sorry, but that's not remotely true. Willow bark (and salicin) antipyretics were known since the 5th century BC, as noted in the aspirin article, and were in use and under development in much of the 18th & 19th centuries.  MCB 23:55, 27 August 2005 (UTC)
thread_title:  History issue

message: In the section on toxicity overview shouldn't it read: "narrow therapeutic index" instead of "low therapeutic index"? This would favourably tie in with the hyperlink to therapetuic index.
:You're quite right. I've changed it. JFW | T@lk 12:28, 5 September 2005 (UTC)
thread_title:  Low therapeutic index? 

message: Per this article, acetaminophen was to blame for 28 percent of the liver poisonings in 1998, but caused 51 percent of cases in 2003. The FDA may "revisit the issue,"  considering that more than 56,000 emergency-room visits a year are due to acetaminophen overdoses and that 100 people die annually from unintentionally taking too much. Is there anything in this which can be folded into this Wiki article? UncleFester 07:37, 28 December 2005 (UTC)
replies: text: The CBS got the statistic from somewhere. Could you recover the original source, e.g. a medical journal article? You did not mention the the absolute increase. Perhaps people took less other hepatotoxic agents (troglitazone was withdrawn in the meantime). JFW | T@lk 13:50, 28 December 2005 (UTC)
thread_title:  Rise in Acetaminophen-linked liver poisoning 

message: The pronunciation is given as [pærəˈsitəmoʊl], which normally would be spelled <paracetamole>.  Is it really pronounced that way?  I'd have thought [pærəˈsitəmɔl].  --Macrakis 19:25, 1 March 2006 (UTC)
replies: text: Maybe it's my Australian accent. =) But that's actually what we use in the clinical setting. For the sake of completeness, however, I'll add the other main pronunciations from the Oxford English Dictionary. -Techelf 10:20, 2 March 2006 (UTC)
replies: text: So you don't distinguish the -ol of 'alcohol' and 'cholesterol' from the -ole of 'indole' and 'thiazole'? Interesting. --Macrakis 15:26, 2 March 2006 (UTC)
replies: text: I say indole as in-dol-AY.. 203.218.91.57 03:26, 26 March 2006 (UTC)
replies: text: That's a pretty unusual pronunciation... -Techelf 07:49, 26 March 2006 (UTC)
thread_title: Pronunciation

message: I have noticed that pharmacy labels (at least here in the United States) usually mark drugs containing acetaminophen with the letters "APAP".  I see that Apap is a redirect term here.  But the term is unexplained.  Can someone add some language explaining what APAP means? --TreyHarris 09:32, 5 March 2006 (UTC)
replies: text: Thanks, I didn't realize until now that the "para" could go on either side of "acetyl", and so I was getting "paap", not "apap". --TreyHarris 06:25, 22 March 2006 (UTC)
thread_title:  APAP 

message: The overview of toxicity notes that a low T.I. makes acetaminophen "relatively dangerous substance," but the fourth paragraph says, "When used responsibly, Paracetamol is one of the safest medications available for analgesia."  While confusing, I can understand how the qualifications on the second statement allow the two taken together to make sense, if one considers all analgesics dangerous.  But I still have a problem with calling acetaminophen "relatively dangerous" -- dangerous relative to what? Maybe this could be described some other way.   Prithason 05:19, 17 March 2006 (UTC)
thread_title:  Contradictory safety statements 

message: I think it would be interesting if a more clued up person to put a bit in about how paracetamol increases the analgesic effect of other drugs.
For example:
1000mg of paracetamol gives mild-moderate pain relef
60mg of codeine gives mild pain relief (no it really is just mild reliefe- taken oral, codeine does not actually provide a large reliefe to pain)
Where as combined they are able to give powerful pain relief.
Part of problem is that whilst most doctors perscribe such combinations (e.g. co-codamol, co-dydramol and before its withdrawal co-proxamol) and patients report better pain relief, the advice from UK Department of Health has often been that studies have failed to confirm the additional benefits over paracetamol alone, nor therefore the additional costs of combination products. This is at varience though with "common experience" when elderly patients´ complaint of increased pain is not infrequently due to taking tablets from their old paracetamol container rather than their newer combination product prescribed the previous week. Anyone else got any thoughts, and then we can perhaps cite some references to add a suitable NPOV comment. David Ruben  Talk  22:11, 25 March 2006 (UTC)
replies: text: I remember reading criticism somewhere saying that APAP/codeine products have never actually been shown to be more effective than acetaminophen alone. I believe similar criticisms have been made about propoxyphene products. I don't have any references, though. --Bk0 (Talk) 00:26, 26 March 2006 (UTC)
thread_title:  Paracetamol as a "booster" 

message: A line in this article states
    "In normal doses, paracetamol does not...affect blood coagulation"
While correct for one off doses, the Australian Medicines Handbook, or AMH, states that in doses above 3.5g per week, an increase in the International Normaised Ration (INR) may occur.  This is substantial enough to warrant a change in the oral anticoagulant, Warfarin.  In elderly patients (likely to be on 4g of paracetamol daily for such things as arthritis), I feel this is significant.  Any thoughts??
:The article passage is correct – paracetamol does not have any effect on coagulation per se. The statement you quoted from the AMH concerns a drug interaction between warfarin and paracetamol (i.e. prolonged use of paracetamol doses can increase the anticoagulant activity of warfarin). -Techelf 12:56, 22 May 2006 (UTC)
thread_title:  Effect on coagulation 

message: Tylenol has been suggested to be merged into this article. Tylenol is a brand while Paracetamol is the name of the drug. I think they can manage as seperate articles, but if they can be merged seemlessly, then I'm for it. --Chris 14:08, 5 June 2006 (UTC)
thread_title:  Merge with Tylenol 

message: Up to 40% of chronic paracetamol users have abnormal liver enzymes. JFW | T@lk 21:05, 4 July 2006 (UTC)
thread_title:  Abnormal LFTs 

message: I think that the opening paragraph should be changed to remove reference to "minor aches and pains." Paracetamol is an highly efficacious analgesic useful in many serious conditions and the public perception that it is weak is both a barrier to proper utilisation of this drug and also a contributor to the frequency of dangerous overdose of paracetamol. It is not just appropiate for slight pain, and even in severe pain where paracetamol is insufficient alone it is highly beneficial in allowing safe and adverse-effect free sparing of other analgesics such as opioids. I'm always eager to get my patients settled into a routine dosage of paracetamol before advising risky NSAIDs or opioids which have many side effects. What does anyone else think about this? Thanks, ben 16:06, 8 July 2006 (UTC)
replies: text: Good point, but if we stated, without your quite correct fuller explanation, "useful for severe pain" then this would also be incorrect for a larger majority of users (most use of paracetamol will be for minor conditions) - and your full explanation would be too lengthy in the introduction. So how about this addition to indicated that in combition useful for severe pain (I've left exposed the wikimarkup for easier copy&paste to the article if you agree): "... and other minor aches and pains. It is also useful in managing more severe pains, allowing lower dosages of additional NSAID or opioid analgesics to be used, so minimising overall side-effects."  ?  David Ruben  Talk  22:50, 8 July 2006 (UTC)

text: Cheers, I think that puts it very nicely! ben 08:24, 9 July 2006 (UTC)
thread_title:  Change to opening passage - paracetamol is not only for "minor" pain