1:08 PM
@Mitch with ibuprofen, if you overdose you'll bleed heavily from your stomach. With fentanyl, your respiratory centers in the cerebrum stop firing: You literally forget how to breathe. With acetaminophen, I need to expand a bit further on liver toxicity:
As I mentioned, liver damage and liver failure are not the same thing. When you take normal levels of acetaminophen, metabolism by binding the drug to, say, glucose is responsible for some 95% of acetaminophen metabolism, and metabolism to the toxic metabolite, called NAPQI, around 5%. This 5% is neutralized by the natural antioxidant in your cytoplasm, glutathione. When you OD on acetaminophen, the glucose-binding pathways (called glucuronidation) are saturated, so the ratio is more like
40% glucuronidation, and 60% metabolism by chemical reactions to produce NAPQI. This amount depletes glutathione first, then binds proteins and DNA and whatever it can find until it disrupts vital cellular processes and causes cellular necrosis (meaning unprogrammed cell death).
Since your cell death is unprogrammed, the cell literally burst open, so 1) NAPQI is released into the tissue, 2) lysosomal enzymes and whatever crazy powerful dangerous substances eukaryotic cells sequester into their organelles are released, and 3) immune cells will get angry and come by to start a whole inflammation process of their own, causing further damage.
So even if the liver is superawesome, the damage will be too great and widespread, and it will lead to organ failure.
This type of liver damage is diagnosed when you detect the enzymes in liver cells being released into the blood (ALT/AST), and bile no longer being excreted leading to elevated bilirubin levels, which results in jaundice, fatigue and itching.
When the organ fails though, you have much bigger problems. The liver does not do the myriad of jobs it does. So what happens is when acetaminophen toxicity is not treated, the liver no longer metabolizes ammonia. Ammonia is a small molecule, so released in the blood, it will go everywhere. The worst place it can go to, which it does, is the brain.
It causes cellular changes that results in cerebral edema. Cerebral edema will lead to all sorts of things: Depression of this or that vital center in the brain (like the respiratory center, similar to fentanyl), even brain herniation. Ded.
By definition, liver failure involves altered mental status. It could be confusion, disorientation, or coma.
Untreated drug toxicity (whether dose-dependent, like acetaminophen, or idiosyncratic, meaning that it can happen at any dose, like some herbal supplements) usually stops there and kills you quickly. The pattern is a bit different if the cause of liver failure is, say, viral hepatitis, or alcohol, or worsening cirrhosis.
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