Paracetamol overdose

[Graham Lappin]

In the UK the number of paracetamol that can be purchased in supermarkets is 16 tablets or a maximum of 32 from a chemists.

In the US there are no restrictions I just purchased a pack of 500 acetaminophen (paracetamol = acetaminophen in the US).

There is some evidence that restricting the purchase of paracetamol reduces suicide:

http://www.ncbi.nlm.nih.gov/pubmed/11210057.

The possibility that those inclined to suicide simply switch to some other means however is a little more difficult to assess.

I will declare a view and say that I always thought restricting the sale of paracetamol in the UK was not rational and if anything, irritatingly inconvenient. Is this another case of safety silliness http://www.ukskeptics.com/forum/show...8034#post68034 or a decision made by the legislators based on good science?

[Pebble]

Working a bit from memory here, so don't quote me.

As I remember it, there were a significant number of unintentional suicides especially among young girls. The problem with paracetamol is that for the first few days everything is fine then the lived fails often over 3 or so weeks. It was apparent that many of these people didn't really understand what they were doing, and really suffered a combination of remorse and terror while gradually dying. Case series showed that the number of tablets consumed depended more on ease of access than intent. The other problem was a number of accidents among children, eating lovely white sweets lying around. I don't believe there was anything more rigorous than that, save to say paracetamol overdose has become very rare in the UK now.

[FarSideOfTheMoon]

If you are determined, you are just going to go round the different shops anyway. It isn't hard to find places who sell paracetamol these days. I did read something about this not so long ago, not sure in what context.

But I guess it is useful in preventing accidental overdoses.

[Trinoc]

The only remotely plausible reason I heard for this (on Radio 4, I think) was that going for a walk such as to another chemist to get some more pills is very effective at lifting a suicidal mood.

Anyway, all they need to do with paracetamol is put on a prominent label saying "If you want to kill yourself, don't use paracetamol. It takes a week to work then you die of liver failure, and if you've changed your mind it's too late. Use something that works faster."

[polomint38]

Why is there no analgesic in the jungle?
Because the Parrots-eat-em-all

How much would be needed for an overdose, is it related to body size or other factors?

P.S. interest only, not planning on trying myself, that would be a loss that humanity would never get over.

I tried suicide on paracetamol once, but after the first 2, I felt fine.

[Mojo]

In the UK the number of paracetamol that can be purchased in supermarkets is 16 tablets or a maximum of 32 from a chemists.

According to this, a single dose of over 10g can cause toxicity. Since the tablets are 500mg each, restricting purchases to 32 seems a bit pointless.

[Trinoc]

What's the rate of removal from the body? Or, to put it another way, if you took the stuff every day, how much would you have to take a day to cause a toxic build-up?

(I ask because, even though I'm one of the people for whom paracetamol has almost no analgesic effect, I find that half a tablet helps me to sleep better.)

[Pebble]

What's the rate of removal from the body? Or, to put it another way, if you took the stuff every day, how much would you have to take a day to cause a toxic build-up?

(I ask because, even though I'm one of the people for whom paracetamol has almost no analgesic effect, I find that half a tablet helps me to sleep better.)

http://www.mja.com.au/public/issues/...l10916_fm.html

Paracetamol is rapidly absorbed from the small intestine. Peak serum concentrations occur within 1–2 hours for standard tablet or capsule formulations and within 30 minutes for liquid preparations. Peak serum concentrations after therapeutic doses do not usually exceed 130 μmol/L (20 mg/L). Twenty per cent of the ingested dose undergoes first-pass metabolism in the gut wall (sulphation). Distribution is usually within 4 hours of ingestion for standard preparations and 2 hours for liquid preparations. Volume of distribution is 0.9 L/kg.2
Further elimination occurs by hepatic biotransformation. After therapeutic doses, the elimination half-life is 1.5–3 hours. About 90% is metabolised to inactive sulphate and glucuronide conjugates that are excreted in the urine. Metabolism of the remainder is via cytochrome P450 (chiefly 2E1 and 3A4) and results in the highly reactive intermediary compound N-acetyl-p-benzoquinone imine (NAPQI). In normal conditions, NAPQI is immediately bound by intracellular glutathione and eliminated in the urine as mercapturic adducts.3
With increased paracetamol doses, greater production of NAPQI may deplete glutathione stores. When glutathione depletion reaches a critical level (thought to be about 30% of normal stores), NAPQI binds to other proteins, causing damage to the hepatocyte. Glutathione depletion itself may also be injurious.3

[Mulder]

If you are determined, you are just going to go round the different shops anyway.

Something which I do regularly because I like to keep a stock to last for a while. I don't want to go out to the shop just because I have a headache.

But I guess it is useful in preventing accidental overdoses.

Given the above, I would say, no it isn't. The whole thing is just another pointlessly annoying aspect of the nanny state.

[Trinoc]

http://www.mja.com.au/public/issues/...l10916_fm.html

Paracetamol is rapidly absorbed from the small intestine. Peak serum concentrations occur within 1–2 hours for standard tablet or capsule formulations and within 30 minutes for liquid preparations. Peak serum concentrations after therapeutic doses do not usually exceed 130 μmol/L (20 mg/L). Twenty per cent of the ingested dose undergoes first-pass metabolism in the gut wall (sulphation). Distribution is usually within 4 hours of ingestion for standard preparations and 2 hours for liquid preparations. Volume of distribution is 0.9 L/kg.2
Further elimination occurs by hepatic biotransformation. After therapeutic doses, the elimination half-life is 1.5–3 hours. About 90% is metabolised to inactive sulphate and glucuronide conjugates that are excreted in the urine. Metabolism of the remainder is via cytochrome P450 (chiefly 2E1 and 3A4) and results in the highly reactive intermediary compound N-acetyl-p-benzoquinone imine (NAPQI). In normal conditions, NAPQI is immediately bound by intracellular glutathione and eliminated in the urine as mercapturic adducts.3
With increased paracetamol doses, greater production of NAPQI may deplete glutathione stores. When glutathione depletion reaches a critical level (thought to be about 30% of normal stores), NAPQI binds to other proteins, causing damage to the hepatocyte. Glutathione depletion itself may also be injurious.3

So, as I'm not an expert in understanding clinicalese but I think I understand half life ... assuming worst case half life of 3 hours, doses 24 hours apart should only be supplemented by at most 1/256 of the previous dose and negligible amounts of previous doses. Correct?

[Pebble]

So, as I'm not an expert in understanding clinicalese but I think I understand half life ... assuming worst case half life of 3 hours, doses 24 hours apart should only be supplemented by at most 1/256 of the previous dose and negligible amounts of previous doses. Correct?

Good way of looking at it - though absorbed dose rather than administered, so only nanomolar concentrations still present after 1g dose, by 24 hours. Even at 1g six times per 24 hours don't get accumulation.