OT:Poisons ...

[Johny B Good]

Rather sadly, they used this excuse to withdraw the very fine painkiller variously known as Distalgesic and Co-proxamol back in December 2007.

The Zapain capsules (Cocodomol) prescribed to replace the initial paracetemol substitute have even worse side effects and hazrds.

And, a mere 24 hours or so to irreversible liver failure from a large[1] paracetamol overdose. The victim usually doesn't feel any immediate effect, it justs destroys their liver after about 24 hours by which time the victim may well have had a change of heart in their self inflicted demise which is rather unfortunate since by then, they've signed their own death warrant that only the miracle of an immediately available liver transplant can revoke.

Staggeringly, there's an antidote that can be included as an extra ingredient in the tablet or capsule which will eliminate the death by liver failure without compromising the pain killing benefit of the paracetamol.

I say staggeringly because whilst ordinary paracetamol is now outlawed in the US of A with only the safe formulation being allowed, the UK still allow the dangerous form to be prescribed and used in OTC medications, which, considering their health and safety concerns in banning a perfectly good painkiller, co-proxamol, seems to be a serious shortcoming in our H&S obsessed culture of UK government.

When I mentioned the "Safe Paracetamol" to my GP, he seemed totally unaware of its existence which gave me a rather shocking insight into the fallabilty of the medical profesion.

[1] What's considered to be a large overdose depends on the individual. Most folk can survive an overdose of a dozen or so 500mg tablets if given prompt treatment with the first hour or two. With some indiviuals it may only be a matter of taking half a dozen such tablets to place themselves at risk of death by liver failure.

The problem with Paracetamol is its low therapeutic to toxic dose ratio. Most drugs are essentially poisons which simply provide a therapeutic benefit at very low sub toxic dosages often with a much higher ratio between these two dosage levels.

[Johny B Good]

In as little as ten seconds on account it locks onto the haemoglobin molecule effectively starving the organs of oxygen. I think an OU lecturer mentioned that potassium cycnaide reportedly tastes like common table salt.

[Bob Henson]

Not so. Co-proxamol was the favourite drug for suicide before it was taken off the market because of its narrow therapeutic ratio - very few were needed to cause death - particularly combined with alcohol. It was no more effective as a pain killer than the other safer opiates, so it was withdrawn.

There is (or was, I don't know if it's still around) , but I never saw any in 50 years in pharmacy. Adding methionine was dubiously effective, it is hepatotoxic in its own right, and pushed the cost up hugely, so there was never any interest in it. It isn't included in the BNF, and most doctors will not have heard of it.

[Nightjar]

On 29/04/2014 19:10, Bob Henson wrote: ...

My partner would disagree with your there. She carefully hoards the co-proxamol she gets on prescription for when her back is really painful.

Colin Bignell

[Vir Campestris]

And yet here we are a selection of interested laymen, and we know about it.

Which is why I take aspirin. I'd rather have ulcers.

Andy

[Mark]

The median toxic single dose for paracetamol toxicity is between 8 and 10 grams (for 'normal' sized adult with the usual variability). As the therapeutic dose is 1 gram the therapeutic ratio is at least 8:1.

I must admit to having a soft spot for paracetamol toxicity for two reasons:

1) the drug itself is not toxic - the problems are caused with a minor oxidation pathway catalysed by cytochrome P450 in the liver. I find it mildly amusing that a system that is typically used to detoxify substances can have unintended consequences. 2) the paracetamol to NAPQI conversion made up a large part of the final viva for my degree.

[Mark]

I believe you may be confusing the mechanism of action of Carbon Monoxide w ith that of cyanide. CO acts in the way in which you describe but cyanide works by decoupling the electron transport chain within the mitachondria wi thin cells. This means that aerobic respiration ceases within the cell thu s effectively stopping energy production with the cell.

[Bob Henson]

Surely she doesn't still get them any more? They are no longer licensed and haven't been generally available and/or prescribed for a long time - several years. There were/are always a vociferous few who insist that they know better than medical science and that "their" drug is better than any other - otherwise there would be no homeopaths left by now - but all the patients I knew eventually stopped whingeing and got on with the new ones just fine. As a long-term, serious arthritis sufferer, if I thought they were any better than anything else I would be whingeing too - I'd do anything that might help with the pain - but they aren't.

[Bob Henson]

Paracetamol is fine within the recommended dosage range. Anything is dangerous taken to excess. I'm quite happy taking paracetamol, but my doctor and I are very nervous about the NSAIs I have to take to stay mobile.

[Nightjar]

TBH I don't recall when she last got a prescription for them. I suspect a lot of things in her drawer full of medications are well past their use by date.

I wouldn't dismiss the effects of belief in a cure, particularly in overcoming symptoms like pain.

They might be, if you believed they were :-)

Colin Bignell

[tony sayer]

Our then 4 Year Old daughter had a cold and was given the universal children's remedy for all aches and pains, Calpol !..

However later that evening we noticed a lot of the packets it came in were in the bin despite them being stored on a high shelf. Young madam had surmised that if you took more of the "medicine" then surely you'd feel more "better";?..

We don't know quite how much she had and as she was asleep at the time however we rushed to her to the local hospital and they in turn contacted the national poisons dept and after a lot of calculations of body weight etc decided that she might have got away with it!.

Seemed she'd taken a small chair and put that next to a bar stool and climbed on the one to get onto the other then climbed onto the worktop and on that reached the top cabinet.....

Where we assumed they'd never be able to get at them;!...

[Huge]

And welcome to it.

[Vir Campestris]

The antidote to methanol poisoning is ethanol.

It's the breakdown products that kill you, and enough ethanol slows down the breakdown of the methanol by competing for the enzyme.

Andy

[Bob Henson]

I hope no-one believes that nonsense and drinks methylated spirits.

[Ferretygubbins]

There are two mechanisms to methanol toxicity - direct CNS toxicity in the same way as ethanol (and any other alcohol) and by metabolisation to formic acid by the enzyme alcohol dehydrogenase. This enzyme can be competitively inhibited by ethanol. This metabolism can be reduced by up to 90% by an equimolar dose of ethanol. (*)

Cheers

Mark

(*) For further details see Principles of Biochemical Toxicology - J A Timbrell

[a_lurker]

It's perfectly true. The same is true for ethylene glycol poisoning, which is probably more common.

You still don't want to drink meths, though -- it contains much nastier things than methanol (pyridine, for example).

[Bob Henson]

The pyridine is there because it tastes unpleasant. The methanol will kill you quite easily, regardless of the presence of large amounts of ethanol. Have a look at the toxicology comments re methanol, and then tell me that ethanol will save you from the effects of it.

[Bob Henson]

You telling me that anyone can drink meths with impunity? Don't be so daft.

[a_lurker]

From which: "Methanol poisoning can be treated with the antidotes ethanol or fomepizole. Both drugs act to reduce the action of alcohol dehydrogenase on methanol by means of competitive inhibition, so it is excreted by the kidneys rather than being transformed into toxic metabolites."

I knew of a case, many years ago, where an individual was in the habit of throwing after-work parties at which he made up the first drinks with methanol instead of ethanol, in order to get the participants 'lit up' more quickly. He got away with this for some time, because the drinkers would then go on to consume large amounts of ethanol-based drinks. Eventually, of course, the practice came to light when two people left early after only a couple of drinks; one subsequently died, and one was left blind.

[Ferretygubbins]

I made no comment about impunity. I merely pointed out the two mechanisms of methanol toxicity. As it happens I think I will defer to the information contained within respected textbooks (as quoted above) that mirrors that given at the Toxicology Department (*) at the London School of Pharmacy both of which are now sadly defunct.

(*) As Professor Timbrell was head of department at the time it is hardly surprising that his text book mirrors the information given in his own lectures.