A few extra tablets can cause cumulative paracetamol [acetaminophen] overdose

[size=+1]A few extra tablets can cause cumulative paracetamol overdose[/size]
Taking just a few extra paracetamol tablets a day over time could lead to a dangerous overdose and even death, a new study suggests.

Paracetamol overdoses are the leading cause of acute liver failure in Britain, usually occurring when patients take a vast number of tablets all at once.

But doctors are concerned that patients who take just slightly too many pills on a regular basis could be at even greater risk because their problem is harder to spot.

People who arrive at hospital having taken a single overdose can often be saved because blood tests reveal instantly how much of the drug is in their system, enabling doctors to act fast to save their liver.

But those who innocently exceed the recommended daily dose of eight 500mg tablets on a regular basis to cope with chronic pain may simply report to hospital feeling unwell, and not mention how many pills they have been taking.

Despite having similar levels of liver damage, blood tests might only show small amounts of paracetamol in their system meaning doctors may not spot the life-threatening problem, experts said.


Full article: http://www.telegraph.co.uk/health/h...an-cause-cumulative-paracetamol-overdose.html

I want info on whether taking N-acetyl L-cysteine (NAC) with paracetamol nullifies the danger. The last time I got a Vicodin script I took 1800 mg of NAC along with it. Is that enough to neutralize all the toxic byproduct? Is it too much? NAC is what is given in hospitals to treat paracetamol overdoses.

People look at me like an extra-terrestrial when I tell them that most people that die from Vicodin do so because of the Tylenol. The public perception is still that Tylenol is one of the safest drugs available. It is, after all, what is given to children for pain and fever.

Though it's true that NAC is the antidote for APAP poisoning, it is run IV continuously until liver enzymes/coagulopathy is corrected. Unless you have the mystical luxury of constant metabolic testing, I'm afraid there is no good answer as far as a prophylactic regime. APAP overdose is no joke, and I sincerely hope you aren't taking enough Norco/Vicodin/etc to kill you (not to be an overdramatic nag, but I've seen enough people fatally fuck up their liver).

^I've read case reports where it's given orally. At least I'm pretty sure I have (I'll look for these). Anyway I just take it for sub-toxic doses like anything up to 4.5 grams. It works really well for some of the oral anabolics, and I suppose it does something for APAP ingestion that's not quite high enough to ferry yourself on over to the ER.

edit: yeah see NAC is often given orally in ERs: http://www.ncbi.nlm.nih.gov/pubmed/20095817 (though I have no idea why)

They are supposedly pulling the 500mg tablets here in the USA at some point (and kudos for that). Isn't codeine or DHC available in the UK, though? I would think that people would just take the stronger painkiller, but I guess the information probably isn't available for them to make informed decisions...

Pegasus said:

They are supposedly pulling the 500mg tablets here in the USA at some point (and kudos for that). Isn't codeine or DHC available in the UK, though? I would think that people would just take the stronger painkiller, but I guess the information probably isn't available for them to make informed decisions...

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I'm fairly sure that the UK has similar laws to Aus, which dictate that codeine/DHC can't be sold otc without an addition ingredient (usually paracetemol or ibuprofen) included. Also, the doses are low, so to consume a decent dose of codiene you need to either CWE (which 99% of the population are completely ignorant of) or take a large dose of paracetemol with it.

It's also much more expensive (here a box of pills with 500mg paracetemol/8 - 10mg of codeine will cost 5 - 8x what a box of plain paracetemol will).

No, the 500mg tabs of plain APAP will stick around, though the makers of brand name Tylenol are voluntarily reducing the recommended daily max to 3000mg. They are lobbying generic manufacturers to follow suit, so we'll see about that. The big news is that prescription narcotics will be capped at 325mg APAP (I think it will officially go into effect in 2014 or 2015, I'm sure one of you know). Most doctors have stopped writing for anything but Norco, and hospitals are no longer stocking Vicodin etc. If they would only stop putting it in altogether, and leave it out of every OTC product while they are at it...

And we just figured this out? After the millions of overdoses and thousands of deaths?

FUCK. DO YOU THINK CIGARETTES MIGHT BE CAUSING ALL THIS LUNG CANCER GUISE?

I hate APAP more than I hate Datura.

Worthless fucking drug. All nsaids should be stricken, shamed, and driven across the land.

A naproxen allergy gave me horrible boils. Vicious drugs.

panic_the_digital said:

Most doctors have stopped writing for anything but Norco, and hospitals are no longer stocking Vicodin etc. If they would only stop putting it in altogether, and leave it out of every OTC product while they are at it...

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They arn't going to top putting it in altogether though. The problem is pure hydrocodone is a Schedule II drug, you need to add some APAP to make it Schedule III. Schedule II drugs are more of a hassle to prescribe because of more regulations (triplicate scripts, can't phone it in, etc)

villian said:

They arn't going to top putting it in altogether though. The problem is pure hydrocodone is a Schedule II drug, you need to add some APAP to make it Schedule III. Schedule II drugs are more of a hassle to prescribe because of more regulations (triplicate scripts, can't phone it in, etc)

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I know well enough, just wishful thinking. APAP is a pretty shitty drug, unless you are old and have bad kidneys or blood pressure. Addressing the hassle issue, I can tell you from personal experience that they are a pain to dispense too, as they grind workflow to a halt to count out and document. There is no one else I can think of that has as much regulatory bullshit to deal with than a pharmacist.

panic_the_digital said:

No, the 500mg tabs of plain APAP will stick around, though the makers of brand name Tylenol are voluntarily reducing the recommended daily max to 3000mg. They are lobbying generic manufacturers to follow suit, so we'll see about that. The big news is that prescription narcotics will be capped at 325mg APAP (I think it will officially go into effect in 2014 or 2015, I'm sure one of you know). Most doctors have stopped writing for anything but Norco, and hospitals are no longer stocking Vicodin etc. If they would only stop putting it in altogether, and leave it out of every OTC product while they are at it...

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Yeah, I think you're right, on second thought... (I'll look for the article in a bit to get the guts of it)

Worryingly, I have a friend who takes a handful of paracetamol before he starts drinking as he feels it makes it easier for him to get drunk. He probably does this about 3 times a week .

Tell your mate not to eat before he goes drinking. May not be exactly harm reduction, but it beats destroying your liver with APAP.

Eat Glucuronolactone to promote Glucuronidation!

235360287471352662 said:

I want info on whether taking N-acetyl L-cysteine (NAC) with paracetamol nullifies the danger.

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Hi,

My take on this is that NAC intake will in fact suppress some of the toxicity of paracetamol/acetominophen (APAP), but not wholly.

My suggestion would actually be to ingest a bolus amount of a compound called "glucuronolactone", readily available from nutritional supplement retailers.

From what I'm reading, conjugation of glutathione (GSH), which is the downstream, active product of NAC consumption, only accounts for ~15% of APAP metabolism, that implies that up to 85% or more of APAP is not going to be cleared by consuming NAC.

However, glucuronidation accounts for about ~40% of APAP metabolism, and this process clears the parent form of APAP before the damaging, electrophile/alkylating form of APAP can even be formed.

Quote from Wiki:
http://anonym.to/?https://en.wikipedia.org/wiki/Paracetamol#Metabolism

* Glucuronidation is believed to account for 40% to two-thirds of the metabolism of paracetamol.

* N-hydroxylation and rearrangement, then GSH conjugation, accounts for less than 15%.

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Thus, consumption of glucuronolactone and clearance of APAP by glucuronidation prevents the toxic form of APAP from being produced, while NAC consumption and GSH conjugation helps scavenge the toxic form of APAP once it is already formed.

A wise bet might be to consume NAC to promote GSH conjugation of the toxic form of APAP, but also consume glucuronolactone to promote glucuronidation and excretion of APAP through a wholly different and much more robust pathway.

^Thanks. I had to delete the source link cuz even though it's not psychoactive it's not allowed.

panic_the_digital said:

Tell your mate not to eat before he goes drinking. May not be exactly harm reduction, but it beats destroying your liver with APAP.

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He doesn't eat either, he stands by the motto 'eating is cheating'. The paracetamol thing is really silly tho, he has been doing it for years. Also, he often gets headaches (so he claims) and whenever I get in his car there is like 50 pills of codeine/paracetamol and he gets through a lot a day. Whether he is addicted to the codeine or not I dunno, but I know he does a CWE sometimes. heh. He is a weird guy.