DrugBuyers.Com: drugs and your body chemistry

I posted some info from websites on this topic in another forum, so I have copied that post to put here.

There are some good websites that discuss the APAP issue & I'll post some links here:

http://www.tylenol.com/products/adult/detail.jhtml?id=tylenol/products/adult/regularextra.inc
Let's start with Tylenol's website - not that it is the most straightforward place to get this info!

If you put together the info in the table "take 2 tablets every 4 to 6 hours as needed" and "do not take more than 12 tablets in 24 hours" for the regular strength Tylenol with the info on the dose of acetominophen in regular strength Tylenol - 325mg per tablet, then you get (do not take more than 3900mg in 24 hours). One thing that they should stress here is that you also should not take more than 750mg in any 4 to 6 hour period. BUT for some people, 750mg taken in a 4 to 6 hour period is too much (even if they have not had alcohol). BTW, these were adult doses.

http://www.carefulparents.com/tylenol.htm
This site addresses the dangers of tylenol in children, but the same concepts apply to adults. For the parents of young children out there, I recommend bookmarking this website to consult for all kinds of safety info regarding children. It has some links to other useful websites as well.

http://www.medicinenet.com/Tylenol_Liver_Damage/page1.htm
This website has a lot of info including explanations about how APAP is metabolized and how it can become toxic AND signs of APAP poisoning and what to do. You may want to bookmark this one for future reference. I don't agree with the position they take that usual doses of APAP rarely cause significant liver damage. There is no such thing as insignificant liver damage! The liver cannot regenerate, so any damage it suffers is cumulative. If you take pain killers with APAP regularly, like many of us do, then every little bit of damage will eventually add up to significant damage given enough time. Also, I take issue with them saving up for a little blurb at the end that even doses that are not much larger than the max recommended doses can cause serious injury or death in some people. This website is worth a read though. If you don't want to read that website, then just have a look at this paragraph from it:

"How does an overdose of acetaminophen cause liver injury?

The answer is that liver damage from acetaminophen occurs when the glutathione pathway is overwhelmed by too much of acetaminophen's metabolite, NAPQI. Then, this toxic compound accumulates in the liver and causes the damage. Furthermore, alcohol and certain medications such as phenobarbital, phenytoin, or carbamezepine (anti-seizure medications) or isoniazid (anti-TB drug) can significantly increase the damage. They do this by making the cytochrome P-450 system in the liver more active. This increased P-450 activity, as you might expect, results in an increased formation of NAPQI from the acetaminophen. Additionally, chronic alcohol use, as well as the fasting state or poor nutrition, can each deplete the liver's glutathione. So, alcohol both increases the toxic compound and decreases the detoxifying material. Accordingly, the bottom line in an acetaminophen overdose is that when the amount of NAPQI is too much for the available glutathione to detoxify, liver damage occurs."

http://www.canoe.ca/Health0103/26_pain-ap.html
This website so aptly says what I have been trying to get across that I'm going to paste the article here:

Acetaminophen overdose worries
By LAURAN NEERGAARD -- The Associated Press

WASHINGTON -- Evidence that many North Americans may poison their livers by unwittingly taking toxic doses of acetaminophen has the U.S. government considering if consumers need stiffer warnings about the popular over-the-counter painkiller.

It's not the first time acetaminophen, best known by the Tylenol brand, has drawn concern. There are warnings not to take it if you consume more than three alcoholic drinks, because the combination can poison your liver.

But the latest worry is about overdoses: taking too much for too long, or mixing the myriad acetaminophen-containing headache, cold/flu and other remedies, or just popping extra pills.

Because acetaminophen is nonprescription, people think "it must be safe and they take it like M&Ms," says Dr. William Lee of the University of Texas Southwestern Medical Center in Dallas.

Lee's data suggest acetaminophen overdoses could be a bigger cause of liver failure than some prescription drugs recently banned for liver poisoning, such as the diabetes medicine Rezulin.

He tracked more than 300 acute liver failure cases at 22 hospitals and linked 38 per cent to acetaminophen, versus 18 per cent of cases caused by other medications. In a second database tracking 307 adults with severe liver injury -- not full-fledged failure -- at six hospitals, Lee linked acetaminophen to 35 per cent of cases.

Most were accidents and should have been preventable, Lee contends.

The findings surprised Food and Drug Administration officials, who this month began investigating how big a risk the painkiller poses and whether more explicit warnings are needed. They are even seeking data from Britain, where so many people used acetaminophen for suicide that British health authorities now restrict how many tablets are sold at once.

Acetaminophen's liver toxicity "is conspicuous in its magnitude compared to some of the other bad players we've taken off the market," says Dr. Peter Honig, FDA's postmarketing drug safety chief. "We're looking at the data to decide if something has to be done, and what."

Certainly millions of Americans safely take acetaminophen every day. Tylenol maker McNeil Consumer Healthcare calls it one of the safest over-the-counter products and insists liver failure occurs only with substantial overdoses.

"This is not a casual, 'Oops, I took an extra pill,'" stresses McNeil vice-president Dr. Anthony Temple.

And McNeil warns that mixing up doses of infant Tylenol drops with children's Tylenol liquid kills -- the two are not interchangeable. Yet poisonings still occur when parents mix up products and give babies a potentially deadly teaspoon-full instead of a safe dropper-full.

For adults, acetaminophen bottles recommend no more than eight extra-strength pills in 24 hours, and to seek help for overdoses.

Critics want labels to mention liver failure explicitly, saying consumers don't realize overdosing is easy and dangerous.

On the other hand, some FDA officials worry that too-explicit warnings could alert potential suicides to the worst doses, causing a problem such as Britain faced.

To be safe, Lee advises limiting daily acetaminophen to the amount in four extra-strength pills, 2 grams total from all medicines.

Overdoses can be treated easily if doctors know the culprit in time. But initial symptoms are flu-like and doctors may not promptly test for acetaminophen's hallmark sky-high liver enzymes.