Sciencemadness Discussion Board - Acetaminophen: How does it work?

Acetaminophen: How does it work?

Blind Angel - 16-11-2003 at 21:22

Sorry about my last question post, it wasn't a school work it was only for my personnal interest, anyway i found all the answer so i will make this interogative post an informative one.

Question mark (?) mean part that i wasn't able to translate of possible bad translation

Pharmacology: Acetaminophen, also know as paracetamol, is a synthetic derivative of the p-aminophenol. It's also an active metabolite of the phenacetine and of the acetanilide, two other p-aminophenol derivative removed from the market due to inacceptable nephrotic effects.
Acetaminophen is an analgesic agent and an antipyrretic with power and efficacity similar to salicylates.
However, this drugs doesn't have, contrarly to the ASA, anti-inflamatory nor uricosuric (?) property, and it doesn't cause gastro-intestinal ulcer nor (agrégation plaquettaire ?) inhibition.
We believe that the antipyrretic macnism of acetaminophen consist in a direct effect on the thermoregulator center situated in the hypothalamus, effect that would increase the heat dissipation by vasodilatation and swetting.
Even if it's not completly understood, the mechanism of action of acetaminophen proceed, we believe, by the inhibition of the prostaglandine synthetase in the CNS. The acetaminophen little effect on the prostaglandine peripheric system, this would explain the absence of anti-inflamatory.
Pharmacokinetic: [Skipping blood plasma concentration and absorbtion pathway] A small fraction of the acetaminophen is converted in a toxic metabolite by the Cytochrome P450 system. Ce metabolite is then conjugated with the glutathion then rejected via the kidney, but in the presence of a Glutathion depletion due to a strong acetaminophen dose, an accumulation happen which, we believe, is the cause of the hepatic necrose induced by acetaminophen (see Overdosing).

[Skipping a big part]

Overdosing: In the adult, the hepatotoxicity may happen after the ingestion of a 7,5g or more, or 150<sup>mg</sup>/<sub>kg</sub> (children) of acetaminophen; a dose of more than 10g can be mortal.
We reported hepatic necrose case induced by the ingestion of 6g and death with dose of 13g. But we also had report of dose between 12,5g and 32,5g without inducing death.

[Skipped the rest]

Personal note: 2 Tylenol extra-strengh = 1g, which is a pretty high dose considering this as a drugs...

[Edited on 17-11-2003 by Blind Angel]

chemoleo - 17-11-2003 at 18:50

Indeed, paracetamol works to my knowledge much like acetylsalicylic acid. It acts by inhibiting the prostaglandin-synthesising enzymes (prostaglandins being a 5-membered carbon ring (2 hydroxyl or ketone groups sticking off it) with two more or less aliphatic chains coming off, one of which carries a COOH group - dont crucify me on this, there are many types (with many variations), in fact type A to I but all derivatives of prostanoic acid).
Anyway, by inhibiting prostaglanding synthesis, which is the main hormone responsible for swelling, pain etc, one reduces the amount of secondary hormones being produced, which ultimately lead to cell death... and pain! This is why it works.
And this is why it's a reasonably good thing to use as a pain killer (like ASA), it doesnt just suffocate the symptoms (like a lot of medicines do), but it literally reduces self-induced cell death (apoptosis) and aides recovery by avoiding the killing of major cell areas (say, during a skin infection), thus making an infection etc (and of course the pain) less serious.
As a result, ASA or paracetamol are actually good for wound healing (taking aside the effect of blood thinning, which is not a problem for most people but for some who suffer have a mutation in their blood clotting gene)

Besides this, there are studies that say that acetylsalicylicacid (ASA) has the ability to prolong life if taken constantly after the age of 30 or so... partly this is related to the blood thinning (less vasicular disease), but also to the lesser amount of inflammation caused by any sort of damage, be it physical (wounds), chemical (i.e. cigarette smoke, which causes inflammation which in turn aides the progression of cancer - believe me I studied this

)or biological (infection).
The basis of this study is based on those poor individuals (which is probably HALF of us eventually) who are suffering arterial/veneral cloggings, who have to take ASA for preemptive blood thinning and treatment...
For myself, I am taking an aspirin every day. Lets see if it works

(speak to you in 80 years

) (see also http://www.sciencemadness.org/talk/viewthread.php?tid=1011 )

(of course, there are those health fascists that think that ASA is really nasty, due to its effect on the stomach lining... but 1) I never appeared to have a stomach problem and 2) if I was to get an acid stomach, there is plenty of calcium carbonate around that can soothe an acid burn, like Rennies etc...., and 3) I dont think (although I dont know) that acid stomach is life threatening unless you really really overdo it)

ANyway.....
The structure of acetaminophen is
HO - phenyl - NH CO CH3.

I purified it myself from tablets, and was trying to think of some useful purposes.

For one thing, adding a strong acid such as HCL should split the peptide bond (NHCO), yielding paraaminophenole hydrochloride.

How would we go about nitrating this? or doing all sorts of other fun reactions??

[Edited on 18-11-2003 by chemoleo]

Blind Angel - 17-11-2003 at 20:02

Look for Pentryl for the nitratation
And by 1g i mean 1g of Acetaminophen, since Tylenol 500 (which is the Extra-Strengh), contain 500mg of acetaminophen

[Edit] I'm one of those who think that Acetaminophen is much too used nowadays, doctor that doesn't even know what it does use it to threat (without result) inflamatoy pain like bursitis. People take a lot of them for nothing, i don't think that it actually help an headache.

Funny note on doctor: a friend of mine was prescribed Oxycontin (oxycodent), Dilaudid (hydromorphone) and Ratio Emtec (codeine) for a bursitis, and they where wondering why her pain didn't went away. The only anti-inflamatory she had in her pill coktail was Naprosyn (Naproxen), to which she had bad side effect. The point of this is that some drugs tend to be so accepted that their bad point are forgotten, thus more and more people are getting prescribed opiate. This induce more and more overdose/misuse and it's the drugs that is blame (Oxycontin is in the grip of the media now I think)

[Edited on 18-11-2003 by Blind Angel]

chemoleo - 18-11-2003 at 09:28

- pentryl got nothing to do with paraaminophenol (HO-phenyl-NH2). Pentryl is obtained from the nitration of phenylethanolamine, which is Phenyl-NH-C2H4OH..... pz

[Edited on 18-11-2003 by chemoleo]

Blind Angel - 18-11-2003 at 14:36

yes, but you may add an ethanol to paracetamol to get it

KABOOM(pyrojustforfun) had the idea btw, he may have more info

[Edited on 18-11-2003 by Blind Angel]

chemoleo - 18-11-2003 at 15:16

yepp, but then there is still the OH hydroxyl at the para-position!!

oopsi!

KABOOOM(pyrojustforfun) - 29-1-2004 at 20:27

(I just read this thread)
Blind Angel: no. that day we were chating on MSN, u told me you were lookin for hydroquinone (2 make its diMe ether IIRC). then I offered the idea of boiling it in alkaline water to hydrolyse it and then diazotating it then adding an alkaline and boliling again. this was the part that reminded you of acetaminophen... I also told you that I was planning to dry-distill ethanolamine phenolate to see if aminolysis occurs and see if I can get N-phenyl ethanolamine this way. which when nitrated yields pentryl...

Blind Angel - 29-1-2004 at 20:45

Sorry for my misunderstanding, that make more since now that i'm rethinking of it

guaguanco - 29-1-2004 at 21:33

Quote:

Originally posted by chemoleo

(of course, there are those health fascists that think that ASA is really nasty, due to its effect on the stomach lining...

May be Urban Legend, but I have read that a surprising number of people used to get small ulcers from unbuffered asprin tablets. Overall, buffered asprin is about as safe as you can get.
Acetaminophen has a certain amount of toxicity associated with it, due to the formation of Acetimidoquinone
http://www.hypertension-consult.com/Secure/textbookarticles/...

Quote:

How would we go about nitrating this? or doing all sorts of other fun reactions??

Well, 4-NH2C6H4OH is very prone to oxidation to benzoquinone, and you can make various things out of that. You could probably directly nitrate acetaminophen, but I don't know that you'd get picric acid.

Edit: changed URL so it would react. chemoleo

[Edited on 31-1-2004 by chemoleo]

Haggis - 30-1-2004 at 12:09

I've always understood that the regular asprin causes ulcers due to the inroduction of extra acid into the stomach. This never made sense to me, being as how a stomach contains hydrochloric. I thought that a bit of ASA wouldn't matter much, but I was probably wrong, due to the fact that buffered is meant to keep a constant pH. The buffered is usually taked by people with existing ulcers, or people on an aspirin regiment, who take a lot of the drug.

Mumbles - 30-1-2004 at 21:29

Take it from me(a guy with ulcers since age 8). ASA doesn't do anything. I'm not sure exactly why you're not supposed to have asprin. I know it irritates the stomach lining. Any irritation does suck with ulcers. Any non-steriodal anti-inflamitory will irritate/cause ulcers and mess with the stomach. I guess asprin just does it more.

chemoleo - 31-1-2004 at 09:13

Remember in the old days they used salicylic acid instead of the acetylated variant. This apparently was worse on stomach lining, hence the acetylated version was used a few decades later.

Presumably the sodium salt of ASA would be the buffered version? should be a weak base, as NaOH is more basic than ASA is acidic, I should think ...

Kaboom, did you try that little idea of yours?
Distilling ethanolamine phenolate, to get N-phenyl ethanol amine? Slightly off topic I know...

KABOOOM(pyrojustforfun) - 31-1-2004 at 14:13

if I had done I would've spiced my post with it...(I'll make a topic as soon as I do)

reply

tom haggen - 31-1-2004 at 19:32

is there away to synthesize an opiate alkaloid with over the counter products?

Blind Angel - 31-1-2004 at 19:52

The most "opiatic" alkaloid in OTC product is the Dextrorotary isomer of Levorphan, also known as Dextromethorphan, which is a morphinan.
You might like to take a look at this page which is pretty detailled

.
BTW: Dextromethophan has no morphine/heroin/codeine... like activity (this is why it is disponible otc) and i don't think there's a way to turn it in something stronger (maybe playing with the R on the tertiary amine but i think that this work only on the Levotary isomer).

chemoleo - 31-1-2004 at 20:12

Nice link.

Nonetheless let's bring this back on topic- I dont even remotely see what this has got to do with acetaminophen, tom haggen. If you want to follow this up then create a separate thread

PHILOU Zrealone - 1-6-2004 at 14:35

Paraaminophenol, paradiaminobenzen and paradihydroxybenzen suffer all three of high sensitivity towards oxydisers...what HNO3 is...there is modification of the reducing form dihydro to de oxydative quinon form...
NH2-Ar-OH <-ox-> HN=C(CH=CH)2C=O + H2O
HO-Ar-OH <-ox-> O=C(CH=CH)2C=O + H2O
NH2-Ar-NH2 <-ox-> HN=C(CH=CH)2C=NH + H2O
the later forms are more prompt to oxydise further and leave nothing but water, CO2 and NOx

Anyway then the way to go for nitration is via
O=C(CCl=CCl)2C=O which is made to react with NaNO2.
Or to block possible proton jump and quinon formation by derivatisating the NH2 and the OH groups into R2N- and -O-R

:cool:

The_Davster - 20-10-2005 at 18:41

I got to thinking about acetaminophen today, initially wondering if it could be nitrated to form picric acid. Upon research on the net it did not seem possible unless it was hydrolysed by a base, the amine group then oxidized to a nitro, and then further nitrated. In the course of my search I came across this site Well I decided I wanted to try out that reaction, then base hydrolyse the product(the second structure in the above link) to 1-nitro-4-aminophenol for no particular reason, although diazonium salts of it could be interesting.

Although this seems rather straight forward, in the link above, what role does the sulphamic acid play in the reaction? I am thinking it somehow aids the oxidation of nitroso to nitro but am not completly sure. Also, upon hydrolysis with base to 1-nitro-4-aminophenol what would be the best way to separate it from the Na-acetate formed? Not much solubility data available on 1-nitro-4-aminophenol in solvents other than water, in which it is soluble in.

Quince - 20-10-2005 at 20:56

Save your liver, take aspirin instead. (unless you are at risk for Reye's syndrome, or have ulcers)

Globey - 18-9-2010 at 20:51

Quote: Originally posted by The_Davster

I got to thinking about acetaminophen today, initially wondering if it could be nitrated to form picric acid. Upon research on the net it did not seem possible unless it was hydrolysed by a base, the amine group then oxidized to a nitro, and then further nitrated. In the course of my search I came across this site Well I decided I wanted to try out that reaction, then base hydrolyse the product(the second structure in the above link) to 1-nitro-4-aminophenol for no particular reason, although diazonium salts of it could be interesting.

Sorry this reply is like 7 years later, but Field Expedient has a tried and true picric acid method using aspirin a the phenol source, sodium nitrate, and conc. HSO4. Advisable to perform outdoors as NO to NO2 is formed. Oh BTW, amongst other mechanisms, acetaminophen actually reacts with the cannanniboid receptor system. Who would have thought.

[Edited on 19-9-2010 by Globey]

zed - 19-9-2010 at 14:35

Ulcers from aspirin? Dissolve 'em in your mouth, before you swallow. Wash 'em down with a little water.

Your stomach's lining, isn't happy with having a solid-lump of pure chemical, burning a hole in it. Much less likely to be problems, if you dilute the reagent, before adding it to the reaction vessel.