The effect of acetaminophen (four grams a day for three consecutive days)

[speakerz]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894983/

Results

A total of 443 subjects were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114 completed) received placebo. Study groups did not differ in demographics, alcohol consumption, nutritional status or baseline laboratory assessments. The peak mean ALT activity was 57 ± 45 IU/L and 55 ± 48 IU/L in the acetaminophen and placebo groups, respectively. Subgroup analyses for subjects presenting with an elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects attaining a peak ALT greater than 200 IU/L showed no statistical difference between the acetaminophen and control groups. The one participant developing an increased international normalized ratio was in the placebo group.

Conclusion

Alcoholic patients treated with the maximum recommended daily dose of acetaminophen for 3 consecutive days did not develop increases in serum transaminase or other measures of liver injury. Treatment of pain or fever for 3 days with acetaminophen appears safe in newly-abstinent alcoholic patients, such as those presenting for acute medical care.

So alcoholics, who are at a higher risk of acetaminophen related liver injury, took 4 grams per day for 3 days and had no or very little liver enzyme increases and no other signs of liver injury? I don't use opiates unless I'm actually in pain but if I did I would certainly do a CWE. I just found this study interesting..

 

[Jabberwocky]

I don't see what the point of this post is? Don't mean to be rude - perhaps you posted in the wrong section.

 

[trees_please]

I did not find this study interesting.

 

[speakerz]

Sorry. Where should I post it in? The point is that maybe acetaminophen isn't as bad as some people say? Just thought it was surprising considering some people suggested people go the ER after taking 3 grams. If you're in the U.S. without insurance that is easily a thousand dollars.

 

[opium]

i see where your comin from, proof of something nobody really has much experience with... not many people on the forum have experiences with APAP overdoses so i guess this research sheds some light

 

[Swimmingdancer]

I'm not totally sure where this post fits best, but I think it's interesting and I get what you're saying. I just think maybe the way you worded your initial post is what confused people, sometimes you need to spell out your conclusions and questions.

My thoughts: A study of 258 people isn't something to scoff at, but I would say it's still best to be on the safe side when it comes to APAP, because I have known people who have overdosed on less than 4000mg. Acetaminophen overdose is one of the most common poisonings worldwide, and when it causes acute liver failure 30% of people die and 8% require a liver transplant.

Some thoughts about this study:

- Other studies have shown very different results to this one.
- The subjects only took the APAP for 3 days, there could be higher risks from taking it for longer periods of time.
- This study was only in adults - young people have been shown in other studies to be at higher risk.
- The subjects all had liver levels within a certain range, people who didn't were excluded, so we don't know what the results would have been for those whose levels were not in that range.
- I don't know what the gender or race of the subjects was, although they did say "minority ethnic groups" were represented, but gender/race/genetics can make a difference too.
- Other drugs/drug use could potentially have an effect on the toxicity of APAP. They also didn't study people who were currently drinking alcohol.
- Things like how much you eat is know to affect APAP toxicity (the less you eat the more toxic it is).

I also think it's good to avoid taking a lot of APAP when you don't need to (like when you're only taking it because it's included with an opioid) because high doses or frequent use can cause side effects such as upper gastrointestinal complications, stomach bleeding, and kidney damage, in addition to the risks of liver damage.

 

[Cane2theLeft]

^ great post.

There is a fine line about how drug related topics should be presented- it's good to instill an appreciation for legitimate harms but if you blow a danger out of proportion then people are going to think you are using scare tactics or propaganda and not trust you. We see this constantly with media campaigns about new drug "epidemics" or advertising campaigns (usually targeting young people) attempting to convince you that if you smoke pot, you're going to run over a dozen toddlers on bikes then molest your pet chihuahua.

Another phenomenon we observe constantly (here especially) is people who are addicted to or abusing drugs who want to rationalize their use... claim they NEED the drug for a legitimate physical or mental condition, claim they have always been able to stop if they needed to, claim that the APAP in the percocets they're popping isn't THAT bad.

Addicts are going to rationalize their use no matter what, but I find it's useful to not give them ammunition to do so by posting things like, "maybe acetominophen is not as bad as some people say?" ...especially when, as SD so aptly pointed out, there are mountain ranges of evidence clearly demonstrating otherwise and cherry-picking one study in a specific, limited population with a very narrowly-defined focus is not grounds to extrapolate a general principle such as "maybe acetominophen is not as bad as people say?" from anyway.

Please do more research about a subject beyond a single, limited-study before even considering conclusions that have impacts far beyond the studies' subject.

 

[sekio]

The FDA reccomended limit for acetaminophen dosing in a 24-hour period used to be 4 grams. And young children are actually less susceptible to APAP poisoning (mg/kg wise), because their livers have a higher capacity to detoxify drugs.

This does not really suprise me; the vast majority of the populance can tolerate fairly large doses of acetaminophen (4 g and less) with absolutely no ill effect. There have been cases of people taking utterly reckless doses of APAP (10 grams+) and having nothing but nausea. Most cases of liver damage from "low doses" (2 g and less) comes from chronic usage in the elderly or those with severely impaired liver function.

A study with n=250, most of whom have been exposed to liver-damaging substances before, shoul;d not be discounted because "I know one guy who died after taking 3 grams". This is not, of course, justification to take humongous doses of APAP with any frequency, but I do agree that many people put unnecessary stigma on APAP. While it can be toxic in overdose, or to certain genetically-susceptible or malnourished individuals, I agree that most people's first reaction to a 3g dose of APAP should not be to speed off to the ER.

Similar to other severe adverse drug reactions (SJS, analphylaxis) there is not a lot you can do in the event that shit hits the rotating air distributor but go seek professional help. But otherwise, the general rule of thumb to work with when it comes to acetaminophen toxicity: 150mg/kg, 7 grams, or whatever causes severe diffuse abdominal pain/nausea. For chronic dosing, 1/2 of that. If you're exceeding that limit you need to at least consult a doctor and have regular liver function tests, or in th case of pain, seek an ER doctor.