Acetaminophen: If You Think That’s Hard to Say, Try N-Acetyl-P-Aminophenol

Ah, the drug by many names.  N-acetyl-P-aminophenol is the chemical name of acetaminophen (USA)/paracetamol (Canada, UK).  It’s most common trade name, you may know, is Tylenol.

Acetaminophen, although it does eventually inhibit COX-2 (we think*), is not considered an NSAID. This is because, although it is simply fabulous for reducing fever and producing mild analgesia, it is lousy at anything anti-inflammatory. So we can’t call it a “non-steroidal anti-inflammatory”, get it?   It also doesn’t inhibit platelet production like NSAIDs, so it’s okay to take with blood thinners.  Why, you ask?  Well, as are many things in our world, that is a matter up for debate.  It is possible that the structure of acetaminophen allows for metabolites that have further actions, or for a reduced inhibition of certain COX-2 products.  What we do know for sure is:

1) If you have a fever, acetaminophen is a great way to reduce it

2) If you have some mild to moderate pain, acetaminophen is a great way to kill it

3) Acetaminophen kicks the s*** out of your liver.

Yes, sad but true.  Acetaminophen is metabolized in the liver.  That, in and of itself, is not really the problem.  The problem is that when the CYP450 pathway breaks it down, one of the end products is highly hepatotoxic (hurts the liver).  It’s bad.  But the double insult is that only a small percentage of acetaminophen actually goes through the CYP450 pathway!  Most of it is glucorinidated in the liver, which yields nice, non-toxic byproducts.

This risk of toxicity is SUPER important to remember.  It is dangerous for:

1) People who have been on it a long time (like someone who takes it regularly OTC)

2) People who overdose on it (duh)

3) People who drink a lot (or who take it regularly after a night of drinking…try an NSAID with a greasy breakfast)

4) People with liver disease, liver weakness, or are at risk for either

5) People that are taking other hepatotoxic drugs (there are quite a few)

Fun fact (depending on how you look at it, I suppose):  If someone overdoses on acetaminophen, and you catch them fairly early, there is a drug called acetylcysteine (MucoMyst) that can stop some of the liver damage from occurring.  Acetylcysteine is generally used as a mucolytic** for various mucous-producing ailments, but also happens to have a structure that binds to toxic metabolites in the liver.  What luck!  Emphasis on catching it early, though.  Those poor little hepatocytes have a lot of work to do, and will not last long when damaged!

*There are just so many mysteries.  If you are interested in spending an afternoon figuring this out, might I recommend going to http://www.scirus.com and searching for “acetaminophen pharmacodynamics”.  Make sure the search is limited to published research from the last few years.  Wikipedia also has an interesting article with several fun references at the end.  If you learn some promising stuff, don’t forget to share it with me!!

**Mucolytics break up mucous!  This is particularly important in diseases such as Cystic Fibrosis, in which patients suffer from ridiculously thick and difficult-to-expectorate lung secretions. It just so happens that their effects on toxic liver byproducts are therapeutic.

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