acetaminophen question

I know that technically the lethal dose of acetaminophen is 7-10grams depending on how long apart it’s taken or if it’s taken at once. But does body weight play a factor in overdose and lethality?

Say a 250 man takes ten 500mg Tylenol at once and gets sick and his liver enzymes skyrocket and he almost dies. Would it be the same situation for a 400lb man?

Does it take more to kill someone who weighs more or is it not one of those drugs? In other words, does it function like alcohol/body weight?

gabriela will be in here presently to give a better answer, but my guess (I’m not a doctor, but once upon a time I got a degree in animal physiology) is that it depends on the size and function of the liver, which is what acetaminophen attacks. A person with a larger or higher functioning liver might handle a large dose better than a person with a smaller or lower functioning liver. And, AFAIK, being severely overweight can damage the liver, so your 250 pounder might be better off than the 400 pounder.

I believe you are correct. Weight might have only a lose correlation with the toxic dose. For example, some heavy drinkers have taken a somewhat regular dose, gone into acute liver failure and died rather suddenly. They wouldn’t necessarily have been drinking when they took it but the types of liver damage that alcohol inflicts on the liver doesn’t play well with acetaminophen. That is why there is that warning label on Tylenol these days not to take it if you have X number of drinks a day.

People differ in the ability to metabolize different drugs in the liver a great deal. That is mostly matters in this case so you can’t assign a firm weight scale to it.

**Dope on Dosage **

Still, the LD50 for acetaminophen is listed in units of mg/kg, so there must be at least a rough correlation.

Toxic dose does, in part, depend on body mass, as a drug will partition into cells, intracellular fluid as well as in blood. However, in the case of acetaminophen (paracetamol) poisoning, the liver uses glutathione as part of the metabolic process. Once the glutathione stores are used up, toxic products are made (NAPQI) that begin to raise hell in the cell. After two or three days, liver cells die off, and you along with them.

Currently, my lab is exploring the phenomenon of surviving toxic doses of acetaminophen when the patient has been taking large, non-lethal doses previously.

Vlad/Igor

The liver size isn’t as much a factor as the function. In fact, an especially large liver is more likely to be diseased, making the toxic dose lower than in a normal (sized) liver.

Liver failure is a truly terrible way to die. Vlad/Igor is incorrect in saying when liver cells die you will too.

It can take weeks to die from liver failure. As the liver fails, toxins build up in the blood, causing shaking tremors, confusion, restlessness and massive swelling of the abdomen. The skin becomes yellow/orange, from the accumulation of bilirubin. Since the liver makes several of the components required for blood clotting, bleeding from the bowel becomes problematic. Ultimately every needle stick, every tiny trauma becomes a bleeding crisis.
The restlessness and confusion is an early stage of hepatic coma. It will eventually progress to unconsciousness, and finally, the blessed release of death.

The only treatment, other than liver transplant, is supportive. Examples of supportive care are, replacing the lost blood products and restraints to prevent injury from the restlessness.

Liver transplant isn’t always an option, since many patients die before a compatible donor comes along.
The surgery is complicated. It can take 8 hours to complete. When the patient comes back from surgery, they require tons of blood components. They can ooze for days. They are in ICU for days to weeks after surgery.
If the transplant is successful, the patient has to take anti-rejection drugs for the rest of his life. He can never drink alcohol again. He must be careful to not be exposed to contagious disease, since the anti-rejection drugs compromise the immune system.

^^Wow, sounds like a miserable way to go. Thansk guys !

In cases of non-acetaminophen induced liver failure, yes, death may take weeks or months even. However, in cases of liver failure due to acetaminophen poisoning, death can occur from liver failure as soon as two days after ingestion when treatment is delayed. Even with treatment, death from liver failure can occur as quickly as four days post-ingestion. I’m still looking for mortality data, but below are three papers that address mortality due to APAP hepatotoxicity.

Acetaminophen poisoning can have low survivability.

Epidemiological data.

WHO database mining implicates APAP in hepatotoxic death, without indicating time to death.

Vlad/Igor

I read your cites, and several of the related articles. None gave any indication as to the interval between the time of ingestion and time of death.
From the first cite:

All this indicates is that, of the eleven cases, only two of the six that received transplants survived, and the remaining five died, awaiting transplant.

I’ve cared for several tylenol overdose patients. Most of those who recieved N-acetylcysteine (Mucomyst®) within 12 hours survived, without injuring their livers. The others, while they progressed quickly to liver failure, lived, either until transplant or two weeks or more before supportive care was no longer of any help.

I worked in both pediatric and adult critical care units for over 30 years. If my experience doesn’t conform to national and world averages, I can only say, I’ve been lucky enough to work in especially good facilities.

I apologize if using real-world experience isn’t an acceptable cite.

You are are absolutely correct that with NAC treatment, the chances of survival is good, and that was not clearly reflected in the cites I gave. That is why I appended the comment “I’m still looking for mortality data…” I haven’t found citations yet that have studied the time to death, if there are any. My own experience comes from the toxicology lab, and working side-by-side with clinical chemistry fellows. You have seen one end of APAP poisoning, I have seen the other end, and the truth encompasses both plus the middle.

Vlad/Igor

I did not read any of the cites above, but I treat a number of acetaminophen overdoses each year.

Lethal doses are usually given in units of mg/kg, reflecting the fact that bodyweight is an important factor. 7-10g is more approximate than the blood concentration of Tylenol 4h post ingestion, and afterwards.

Hepatotoxicity is usually seen after days to weeks, but is seen quickly in high doses and is a bad sign.

NAC works in part by increasing glutathione synthesis in the liver, the glutathione is overwhelmed by high doses of Tylenol and APAP gets converted to NAPQI.
http://www.emedicine.com/ped/topic7.htm

Less well studied is chronic hepatotoxicity in patients on, say 5g per day for years.

Bodyweight is also the reason why babies are much more susceptible to poisoning than adults (one pill is often enough when you weigh little) and why most Poison Control Centres are located in large children’s hospitals.

Tylenol poisoning can’t be treated well if it is not diagnosed. NAC is effective perhaps up to 24 hours post-ingestion. People who swallow Tylenol in private or take ample sleep medicines with it are not treated as quickly and do worse.

NAPQI = N-acetyl-para-benzoquinoneimine, which positively rolls off the tongue.
I wonder why they use that cryptic abbreviation? :wink: