When you or your loved ones aren’t feeling well, the first thing that comes to mind is usually ways to manage mild illness at home, without having to go to urgent care or the emergency room. Thankfully, for most illnesses, that is completely feasible. Decades of research have given us options for non-prescription medications that alleviate symptoms of many common ailments.

When we have symptoms such as fever, headaches, menstrual cramps, or muscle aches, there are a variety of different pain relievers (analgesics) and fever reducers (antipyretics) that we can reach for in our own medicine cabinets. While they work similarly, they do have some key differences. Three common options are Ibuprofen, Naproxen, and Acetaminophen.

Pain and inflammation in our body is mediated through multiple processes, but key players are the cyclooxygenase (COX) enzymes. COX-1 and COX-2 produce molecules called prostaglandins, lipid hormones that are synthesized from arachidonic acid. Normally, we have baseline levels of COX activity and prostaglandins, but after injury, increased activity of COX-1 and COX-2 lead to enhanced prostaglandin production.

COX enzymes exist everywhere in the body but are activated and produce prostaglandins at specific sites of tissue damage or infection. Prostaglandins lead to inflammation, pain, and fever (as well as participating in the healing process of our immune system!)

Over the counter pain relievers act upon this mechanism to help alleviate symptoms. 

Ibuprofen blocks COX-1 and COX-2, which reduces the level of prostaglandins wherever in the body they are being produced. This activity subsequently combats inflammation and the pain associated with inflammation.

Similarly, Naproxen also blocks COX-1 and COX-2 enzymes. However, Naproxen lasts longer in the body than Ibuprofen. Ibuprofen has a half-life (the time it takes for 50% to degrade) of about 2 hours, whereas Naproxen has a half-life of nearly 12 hours.

Ibuprofen and Naproxen are considered NSAIDs - non-steroidal anti-inflammatory drugs (NSAID)- because they are not steroid medications, but they do reduce inflammation.

Acetaminophen has been around for longer than Ibuprofen and Naproxen. It was first manufactured in 1878. Ibuprofen was invented in 1961, and Naproxen in 1967. Interestingly, the specific mechanism of action of Acetaminophen is less understood than Ibuprofen or Naproxen - but that doesn’t make it any less effective!

Acetaminophen has fever-reducing and pain-relieving properties but does not have the same level of anti-inflammatory effects as Ibuprofen and Naproxen. It does not act on the COX enzymes, but it appears to work through 2 difference receptors in the brain to reduce prostaglandin levels instead. As a result, is it not considered a NSAID, but rather, a non-aspirin pain reliever. 

So - how do I choose which to take?

If inflammation is the cause of pain (e.g., menstrual cramps, arthritis, etc.) then NSAIDs (Ibuprofen and Naproxen) are probably your best bet since they have more potent anti-inflammatory action. You may also want to consider how long-lasting you need your pain relief to be. If you need something longer-lasting, Naproxen might be the way to go over Ibuprofen (perhaps for overnight relief). 

There are some other considerations that may guide usage.

For example, Acetaminophen should be used carefully in those with liver problems. Ibuprofen should be used cautiously by those with heart disease, high blood pressure, clotting and/or bleeding disorders, stomach ulcers, kidney problems, and the elderly. Ibuprofen should also be taken with food, as it can cause stomach upset. NSAIDs such as Ibuprofen or Naproxen are not typically recommended during pregnancy, whereas Acetaminophen can be used when pregnant.

Further, consuming a small amount of alcohol while taking Ibuprofen is generally not considered harmful, but mixing alcohol with Acetaminophen can irritate the lining of the stomach and intestines.

If you have any specific questions, make sure to consult with your pharmacist and/or primary care physician who are familiar with your medical history!