I know the safe dose is 3-4g a day, and I think the max dose in one sitting is 1g. But how much tylenol in your system before your liver can no longer process it as a non-toxic byproduct?
This claims 4-7 grams (I assume in one sitting). Does anyone have a more official answer?
Well there are a couple of quotes from your link that shed more light right away.
And further reading shows it the excess Tylenol not processed by the liver is turned into a toxin by some other means.
Personally, I won’t touch the stuff anymore. Doctors in the 70s were telling me to take 4 grams a day. Maybe not lethal, but I don’t want to get that close.
What makes you think there’s a single number?
The LD50 depends on animal species tested (I couldn’t find data for humans, unsurprisingly), and is somewhere between 500 and 2,500 mg/kg.
Tylenol becomes a toxin because your liver doesn’t have enough glutathione to convert it into the non-toxic byproduct. In an APAP overdose drugs/supplements that increase glutathione levels are administered like ALA or NAC to process it. However you’d assume there is a window of how much APAP a person’s liver can safely convert into the non-toxic byproduct before glutathione levels deplete and you end up with the toxic byproduct. I get the impression it is about 4-7 grams in the bloodstream based on that link.
beowulff - I am more looking for a window-ish number. There is a massive difference between 2-3 grams at once before liver toxicity starts and 10-15 grams.
There’s a massive difference between livers.
Although the 4 gm figure is usually the one given as the threshold for safety, it’s important to remember that the number can be much lower in those individuals who drink alcohol frequently and in large amounts. In such people, an intake of as little as 2 grams can be fatal.
The main reason for this is due to alcohol’s effect to “induce” (i.e. rev up) the enzyme responsible for breaking down the tylenol. Remember, it’s the breakdown product of tylenol that’s toxic, not the tylenol itself. So, anything that increases the rate of breakdown of tylenol in the body will also have the effect of increasing the rate of production of the toxic products of tylenol breakdown.
(Only somewhat paradoxically, the above notwithstanding, the simultaneous ingestion of alcohol and tylenol, can protect the individual against tylenol toxicity. This is a reflection of the fact that alcohol and tylenol compete for the same enzyme in the liver. They each use/need it for their breakdown. So, if alcohol has tied up all the enzyme, there’s less of the latter available to break down the tylenol to its toxic breakdown product).
From my perspective as an ED physician, the official answer is that the amount of acetaminophen in your system which will precipitate me treating you with the antidote (N-acetyl cysteine) is determined by a blood level and comparing it against the RumackMathews nomogram.
If your blood level falls above that line–for example, if it’s 140 mg/L at 4 hours post-ingestion, I’ll order up the NAC in an effort to protect your liver.
As a rule of thumb, the amount of an acute ingestion (more or less all at once) that will put your blood level of acetaminophen above this line is about 150 mg/kg. But any ED doc will tell you it’s almost never that clean. Most acute overdoses are suicide gestures, so the presentation is not always clean. Underlying liver disease complicates things. People vomit after taking too much acetaminophen. They don’t know exactly when they took it. They boozed up while taking it. They took it on an empty stomach. They took it on a full stomach…on and on.
The antidote treatment guideline is by nature conservative. If you completely rot your liver, you check out of the hospital horizontally unless you can rent a new liver from a donor. So you could probably get by with quite a bit more than 150 mg/kg as a point ingestion, but it’s not a good idea to find out if you are the guy who can.
I believe the current recommended daily maximum for routine use (and not as a point dose) is about 3 grams/day for an adult.
Note that almost all the acetaminophen in your system gets processed with an intermediary toxic metabolite. It’s a question of how much of that metabolite is in your system at any one time.
