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by calebsurfs 2292 days ago
The active dose is nowhere near the lethal dose. It is however close to the dose where you could see some minor damage to the liver. It causes problems because people are addicted to opioid drugs that are typically combined with acetaminophen, not because they are loading up on acetaminophen itself.
2 comments
DanBC 2292 days ago
Paracetamol is dangerous in overdose, and the therapeutic dose is pretty close to the overdose amount. The therapeutic index is approx 10.

Compare that to morphine, which has a therapeutic index of about 70.

(although the therapeutic index is tricky to use because of dose response curves)

We know that paracetamol is commonly used in both accidental and deliberate overdose. And this is true in countries that don't have the opioid crisis, and it was true in the US before the opioid crisis.

> It causes problems because people are addicted to opioid drugs that are typically combined with acetaminophen,

This is part of the problem, yes. But it's incomplete. We know that paracetamol alone causes problems for the liver even with small overdosing. https://britishlivertrust.org.uk/researchers-shed-new-light-...

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arcticbull 2291 days ago
This isn't really a debate:

- "Liver toxicity from acetaminophen poisoning is by far the most common cause of acute liver failure in the United States, researchers reported" [1] in 2005. It was also true before the opioid epidemic really began.

- "The recommended dose of acetaminophen in adults is 650 to 1,000 mg every 4 to 6 hours, not to exceed 4,000 mg in a 24-hour period." [2]

- "Single doses of more than 150 mg/kg or 7.5 g in adults have been considered potentially toxic." [2]

- "The minimal dose associated with liver injury can range anywhere from 4 to 10 g" [2]

The active dose is very close to the dose at which liver damage occurs (4X single dose or 1X daily dose) and also a fatal dose (10X single dose or 2.5X daily dose). Further, it's exacerbated by alcohol use, which is why you should never drink and then take Tylenol.

Wheres, ibuprofen the safety margin is 120X a single dose and 40X a daily dose. For naproxen, it's 63X a single dose or 21X a daily dose [3].

[1] https://www.medpagetoday.org/psychiatry/depression/2233?vpas...

[2] https://www.uspharmacist.com/article/acetaminophen-toxicity-...

[3] https://www.advilaide.com/safety/overdose

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