How does tylenol damage your liver?

Question

I have a power point on Tylenol . I just have to explain that slide about how does tylenol damage your liver?

Please and thank you

Answer 1

Tylenol (acetominophen) is partially metabolized in the liver by an enzyme system they call cytochrome P450 (there are a bunch of different types; the relevant ones for Tylenol are CYP2E1 and CYP3A4, if that is on your slide).  The CYP's job is convert the acetominophen into N-acetyl-p-benzo-quinone imine (NAPQI), which is very highly reactive because of its ability to oxidize.

Normally, NAPQI is immediately neutralized by being conjugated to glutathione.  You don't really have to worry about what that means if you don't want to; all you need to know is that you need glutathione if you are not going to have this dangerous intermediate NAPQI floating around.

If it's not immediately neutralized, NAPQI is toxic to liver cells.  That's how it damages the liver.

Some people have problems with Tylenol because they have varying levels or activity of the cytochrome P450s, and alcoholics deplete their glutathione levels and can overdose on acetominophen at much lower dosages.  Or anybody can run out of glutathione if they take too much acetominophen.

You can replenish the liver's glutathione stores with N-acetyl-cysteine (NAC), which is the antidote for acetominophen overdose.

Answer 2

It doesn't, unless you take it in retarded amounts.

I'm not sure about this because I haven't actually seen it in physiology yet but my guess would be that the liver has to work too much to metabolize it, that produces some kind of hepatitis, and that then evolves into fibrotic tissue similar to cirrosis.

Answer 3

If you need a diagram, of tylenol metabolism, there'sa good one here:

http://www.ch.ic.ac.uk/wiki/index.php/It...

The liver processes drugs to make them more hydrophilic so that they can be more easily excreted in the urine. Tylenol (aka paracetamol, acetaminophen) is harmless to your liver. When someone takes a normal dose, it is mostly processed by a process called glucuronidation, which is carried out by glucuronyltransferase enzymes. This produces a glucuronide conjugate (see the diagram in the link), which is also harmless to the liver and gets excreted in the urine.

When higher amounts of tylenol are taken, the glucuronyltransferase enzymes can't deal with it all, so some other enzymes in the liver decide that they will have a go - the cytochrome p450 enymes that Marie has mentioned. Unfortunately they turn harmless tylenol into very nasty toxic  N-acetyl-p-benzoquinoneimine (NAPQI). Luckily, the liver can normally immediately get rid of this by attaching it to glutathione, which makes it safe again, and it's then excreted.

The problem of toxicity occurs when your liver can no longer get rid of the NAPQI. This happens when you run out of glutathione. If someone takes an overdose or takes a high dose of tylenol for a long time, the glutathione will eventually get used up. This explains why overdoses can cause liver damage after a delay of a few days. The treatment for overdose is to give NAC (the 'antidote' in the diagram), which is used to make more glutathione.

Someone is at much higher risk if the cytochrome p450s are more active than usual - e.g. alchol and other medication will up-regulate these enzymes so more of the tylenol gets metabolised by them, so you run out of glutathione quicker. So a tylenol overdose washed down with alcohol is much more dangerous.