Is Advil smarter than a fifth grader?

I'm so excited for today's post! I don't know if any of you will remember this, but a meme that went viral a few years ago asked, "How does ibuprofen know where your pain is?" For those of you who don't know, Advil is a brand or trademarked name for a medicine whose active drug is ibuprofen. Anyway, I remember seeing the meme and being shocked for a second because I used to be (and kind of still am) someone who resorts to Advil for many of my problems like menstrual pain, headaches, and muscle aches. So I too was now wondering how this one drug can be used to respond to pain in very different parts of your body. How does ibuprofen know exactly where the pain is?!? 

Disclaimer: This post is not intended to give medical advice. If you are thinking about making changes to your current medications, please speak with your doctor or pharmacist.

Our Body's Response to Pain

Before we talk about ibuprofen, I think a good place to start is to talk about when or why it's used - to combat pain. So what exactly happens when you get injured?

When you experience an illness or injury, inflammation is one of your body's protective responses. As a part of this response, the affected cells release something called arachidonic acid which produces prostaglandin. An enzyme called cyclooxygenase-2 (COX-2) is activated and interacts with arachidonic acid to convert prostaglandin to prostaglandin H2 which does many things. For example, it makes the nerves around the affected area more sensitive to pain and results in inflammation and swelling. 

I drew out an example of this in Figure 1 to help me put the above paragraph into perspective. Let's say you were running and you tripped, fell, and hurt your knee. The damaged cells in your knee would release arachidonic acid as well as activate COX-2. These would interact to produce prostaglandin H2. The released prostaglandin H2 would cause the nerves in your knee to be more sensitive to stimuli; so for example, when you touch your knee, the nerves would send a signal to your brain and your brain would tells your body something is wrong, sending the message that you are experiencing pain in your knee. Prostaglandin H2 would also cause the tissue in your knee to become swollen and again, feel painful.

How Ibuprofen Actually Works

Now, let's finally talk about ibuprofen. Ibuprofen is categorized as a non-steroidal anti-inflammatory drug, or NSAID for short. It's used as a temporary, short-term treatment for mild to moderate inflammation-related pain. 

Ibuprofen comes in many forms such as tablets, capsules, or liquid (i.e. as a cream). For simplicity, let's say you took an ibuprofen tablet like Advil. After it's swallowed, it would travel to your stomach where the tablet would dissolve, releasing the ibuprofen. As a result, the ibuprofen would be absorbed into your bloodstream. In the blood, ibuprofen would travel throughout the body until it finds the COX enzymes. When it does, it would bind to the enzyme, inhibiting it and stopping its activity like the production of prostaglandin H2. As a result, there would be lower levels of prostaglandin H2, which means we wouldn't see its effects like nerve sensitivity and swelling. Therefore, there would be less pain and inflammation. This is shown in Figure 2 using the knee example from before.

One thing to note here is that when ibuprofen is in the bloodstream, it does not specifically bind to COX-2. It is not selective for it. This means that it will also bind to COX-1. The differences between COX-1 and COX-2 are outlined below:

• COX-1 - found throughout the body's tissues including the gastrointestinal tract like the lining of the stomach

• COX-2 - found mainly at inflammation sites

Conclusion

Maybe ibuprofen is super smart, but it's definitely not as calculated as it seems. It simply travels throughout the bloodstream and stops when it finds COX enzymes to bind to, regardless of where exactly in the body the enzymes are - for example, in your legs or your fingers. So, I think the main thing I drew from all of this is how smart our bodies are in general. Modern medicine is amazing, and it seems to have a solution for almost all of our health problems. But in order to develop these medicines, we must first untangle the intricate, natural complexities our bodies present.

Things to Consider Before Taking Ibuprofen

I know I probably made ibuprofen seem fantastic, so I just wanted to add some extra information before I end this post.

The Different Types of Ibuprofens

First of all, as I mentioned above, there are different forms that ibuprofen comes in like tablets, capsules, and liquids. There are also different brands that sell medicine which has ibuprofen as the active drug like Advil, Motrin, and Nurofen. The main differences are the exact chemical compositions; although all have ibuprofen as the active ingredient, some may work better for certain people or faster than others. There are also different doses/strengths available. Most ibuprofen are sold over the counter, but there are some stronger ones that require prescriptions and are used to treat more chronic forms of inflammation like arthritis. 

There are also some medicines which combine ibuprofen with other drugs so it's really important to understand each medication you take to make sure it's the right one for what you wish to treat and to avoid accidentally 'doubling up'. For example, if you took Advil and Motrin, not understanding that they are both ibuprofen, you would be taking A LOT of ibuprofen, which may not be healthy for you.

Risks of Ibuprofen

As with anything, taking ibuprofen comes with potential risks. I will try to highlight a few of them here, but I would like to emphasize that this is not a conclusive list. 

Firstly, like I was saying above, ibuprofen inhibits both COX-1 and COX-2. COX-1 is involved in maintaining the stomach lining which is crucial for protecting the stomach from stomach acid. If COX-1 is inhibited by ibuprofen, it is unable to develop the lining which would mean reduced protection of the stomach from stomach acid. This would lead to increased acidity which could result in stomach ulcers and bleeding. 

Taking ibuprofen also comes with risks like damaging your kidney or developing increased blood pressure. Additionally, taking ibuprofen for a long period of time to treat headaches can sometimes result in rebound headaches due to drug tolerance, which is when you need more of the drug to feel the same effects - in this case, relief from the headache.

Tylenol vs. Advil

Lastly, I wanted to quickly talk about the difference between Tylenol and Advil because this is something that I did not understand for a long time. 

As I mentioned, the active ingredient in Advil is ibuprofen. However, the active ingredient in Tylenol is acetaminophen. The major difference is that acetaminophen mainly blocks COX enzymes in the brain. Thus, while it would be able to reduce pain and fever, ibuprofen would be a better candidate for reducing inflammation and swelling in the injured tissues.

Another thing to note is that these drugs block COX enzymes at different locations so technically, they can be taken together. Some people suggest that this could lead to better pain-relieving effects given that this would essentially be like taking a stronger dose. You should still consult your doctor or pharmacist before deciding if this combination is right for you.

Again, acetaminophen has its own risks associated with it like liver damage with prolonged use or use of increased doses so that is also something to consider.

Citations

• Acetaminophen vs. Ibuprofen: What’s the difference? Nationwide Children’s Hospital. (n.d.). https://www.nationwidechildrens.org/family-resources-education/700childrens/2022/02/acetaminophen-vs-ibuprofen-difference 

• Hawkey, CJ. (n.d.). Cox-1 and COX-2 inhibitors. Best practice & research. Clinical gastroenterology. https://pubmed.ncbi.nlm.nih.gov/11566042/ 

• Ibuprofen. healthdirect. (2023, July 3). https://www.healthdirect.gov.au/ibuprofen#:~:text=Ibuprofen%20works%20on%20one%20of,and%20your%20fever%20goes%20down 

• Mazaleuskaya, L. L., Theken, K. N., Gong, L., Thorn, C. F., FitzGerald, G. A., Altman, R. B., & Klein, T. E. (2015, February). PharmGKB summary: Ibuprofen Pathways. Pharmacogenetics and genomics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355401/ 

• Medicines and the digestive system. Johns Hopkins Medicine. (2019, November 19). https://www.hopkinsmedicine.org/health/conditions-and-diseases/medicines-and-the-digestive-system 

• Moon, E. (2020, February 3). How does ibuprofen actually work?. Medium. https://elemental.medium.com/how-does-ibuprofen-actually-work-eb296f179f43 

• What is Ibuprofen & How Does It Work?. Nurofen AU. (n.d.). What Is https://www.nurofen.com.au/pain-advice/about-nurofen/what-is-ibuprofen/