Say you have one of the following: a fever, body pain, a headache or swelling due to an injury. What do you take to feel better? Most people nowadays take one of the following: ibuprofen or acetaminophen. What’s the difference? For a long time I thought there wasn’t much of a difference, but these two compounds work by very different mechanisms.
Ibuprofen ((RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid) works much the same way that aspirin works. It inhibits two enzymes called COX-1 and COX-2 (COX = cyclooxygenase). COX-1 and COX-2 are key enzymes in the production of prostaglandins which are key mediators of inflammation and fever. Excess inflammation in your body causes pain. Most of the anti-inflammatory activity of ibuprofen is due to COX-2 inhibition. Inhibition of COX-1 can cause stomach bleeding in some people although this is usually not a problem.
Acetaminophen is quite different, and it’s mechanism of action is still not completely clear. Instead of being an anti-inflammatory, acetaminophen is mostly an analgesic or anti-pain medication. Only recently has TRPA1, the Transient Receptor Potential cation channel A1 and a key ion channel involved in sensing pain, has been proposed as the target of acetaminophen. Thus if one wants to reduce swelling, acetaminophen is not the way to go. Acetaminophen does reduce fever – for reasons that aren’t apparent to me….just something else for scientists to figure out.
These aren’t the only differences. While both medications are very safe when taken as prescribed, acetaminophen hepatotoxicity (often exacerbated by alcohol consumption) is the most common cause of acute liver failure in the US…something that I should blog more about in the future. Still it’s quite amazing that these two medications that people assume are similar have such different biologies.


Arik Elfassy said:
I ibuprofen works in the same manner as aspirin does it have the same benefit for heart disease as aspirin is purported to have? Thanks, Arik.
on March 7, 2012 at 3:22 pm
Delilah Coe said:
Thanks for the info, Its quite interesting.
on February 6, 2012 at 12:37 pm