Every time I post information on this, I really feel like people just use it as a license to see how much they can push themselves, and that's scary. It's a very individualized thing, and when you are talking about long-term amounts and daily dosing, all we are certain of is that it takes much less to cause toxicity than after a single dose. Long-term OD is a lot different and much harder to guess at any sort of prognosis. Weight, alcohol consumption, genetics, malnutrition (more common than you think), other drugs, liver conditions like hepatitis, age, and the length of time at various doses all play a huge role- moreso than people think, it's not just a simple numbers game where you can plug in figures into a formula and make an educated guess. Students and professionals publish a ton of papers on this very topic. There isn't even a consensus on exactly how the pharmacology works here, and there are a ton of conflicting figures over what is the dose that you can get away with.

What is generally agreed upon is this:

1) There are four stages of APAP toxicity. Every souce you go to has different guidelines on how long these stages take and what the symptoms are, but this is what is generally agreed upon: The first one takes place in the first 24 hours, and those symptoms are severe nausea (moreso than regular opiate nausea), vomiting, anorexia, severe fatigue (moreso than regular opiate fatigue), and upper right quadrant pain. Not having these symptoms doesn't mean you're ok-in other words, you can still be in very bad shape and be virtually symptom-free. The next stage is 1-2 days afterwards, where you may feel better, but if you took an LFT (Liver Function Test), your liver enzymes would be dramatically raised, possibly even surpassing the level of a long-term alcoholic. The next stage is about 3-5 days after the first stage, and that's where liver cells are dying rapidly, and liver enzymes will peak. There is a small chance of dying in this stage unrelated to liver failure. The final stage is a week to two weeks after the first stage and that's when you can develop ALF (acute liver failure) and/or die. If you had gone to the hospital ASAP (within 10 hours for optimal relief, within 36 if that didn't happen), you'd be recovering at this point.

2) Liver failure symptoms are kind of minimal initially- THIS is what people are talking about when they say it comes on very secretively. It's really not much more than bad nausea, fatigue, and opiates have those side effects anyway. It really is worth getting evaluated at this point, as the next symptoms are jaundice (yellowing of the skin/eyes). Confusion, coma, drowsiness, insomnia, and disorientation occur around this time as well- they're caused by hepatic encephalopathy. Basically that's what happens when the liver can't deal with toxic substances in the body, and it begins messing with your brain. You *MUST* get to the hospital at this point. Do not delay if you think you might have a problem or have any reason to believe you would. Again, you MUST get to the hospital if you have jaundice (yellowing of skin/eyes), coma, confusion, disorientation, etc. BY THE TIME YOU HAVE THESE SYMPTOMS, IT IS GETTING PRETTY CLOSE TO TOO LATE! The sooner you get treatment, the better. If get help within the first 12-24 hours, you dramatically improve your chances of recovery. IF YOU ARE EXPERIENCING ANY OF THIS, CALL 911 IMMEDIATELY. THIS IS THE CRUCIAL TIME TO GET HELP. THESE ARE THE MAJOR SYMPTOMS, THIS IS YOUR SIGN IT IS GETTING TO BE TOO LATE!!!

3) Most patients in this situation would not just drop dead all of a sudden without ANY symptoms out of nowhere, but you don't have much time to get help once you start experiencing the more serious symptoms. You could very well, however, develop acute liver failure out of nowhere. The scary thing about APAP OD is that there aren't many warning signs until it's too late. You do not have a very good chance of survival if you wait long enough to get the obvious symptoms of acute liver failure. Your prognosis is significantly better if you get treatment within the first 24 hours. If you wait until you have the obvious signs of acute liver failure, you barely have a 20 percent chance of living. You are likely to need a liver transplant, if you wait this long. Better hope one is available and you haven't done too much damage in the first place. A liver transplant could potentially save your life, but it is not something to rely on. There aren't many livers available for transplant, and the goal of treatment would be to keep you alive until one is.

4) NAC is not a license to abuse APAP. Not even close- yes, it is minimizing the damage (assuming what you bought is reasonably pure- keep in mind that dietary supplements are barely regulated). You should not be taking a huge dose daily- if you are, NAC will prolong the process described above, but it can't stop it. NAC alone cannot save your liver, especially if you aren't dosing correctly and in high enough amounts. It's not something you just take when you get any of the symptoms mentioned above, it must be taken daily and consistently. It may take years to end up with acute liver failure if you are taking huge amounts of APAP but combining it with NAC; it will happen in time. How long varies from person to person by the factors described up top and how you take NAC.

5) If you are taking your meds as directed, you won't have a problem. This applies to people taking large amounts, or slightly smaller than that daily- what the amount is varies from person to person. There is no generally agreed upon figure. To the person who said she took 10,000 milligrams (aka 10 grams), that's too much- if you are doing that every day, your days are numbered. Adding NAC will likely prolong those days, but it won't stop the inevitable. If you are taking a high amount like that daily, you are slowly killing liver cells- if you are on NAC, you are delaying that process.

6) If your opiate tolerance is such that you have to take huge amounts of hydro/apap in order to stay out of withdrawal, you really need to strongly consider getting on Suboxone/Subutex or Methadone. You can't keep up this lifestyle forever; there aren't many reports of long-term APAP abuse because it's not a common thing. With OP's making it so easy to get huge amounts of a drug that is easily abused, I'm predicting that the number of cases from long-term APAP abuse will skyrocket.

Here are some bookmarks if you want to read further. If you do a search on "nac" here or look up any of these threads about APAP, I've given other websites- there is a ton of information about this available.:

http://www.ucdmc.ucdavis.edu/transplant/newsletter/newsletters/spring00/html/liver.html

http://www.ijmt.net/1_3/1_3_19.html

http://ccforum.com/content/6/2/108

http://www.fda.gov/cder/livertox/Presentations/im2917/

http://faculty.swosu.edu/scott.long/txcl/drugtox.htm

-yawkaw