Health Tips

Read Part 2 here.

Painkillers are one of the amazing medical inventions of humankind. While there are many types of painkillers with different strengths and uses, we are going to discuss a particular class of painkiller in this two-part article: nonsteroidal anti-inflammatory drugs (NSAIDs). 

NSAIDs are not only useful for their analgesic properties (ability to reduce pain), but they are also widely used for fever and reduce inflammation (hence ‘anti-inflammatory’ in the name). The reason the phrase ‘non-steroidal’ is included in their name is to distinguish them from steroid, which is another class of medication that can reduce inflammation as well. 

If you know someone who has pain in the joints and is taking medication, chances are that person is taking one of the NSAIDs. Indeed, 14.2% of Malaysian adults use NSAIDs and 4.2% of them use it daily. A study on the analgesic prescribing pattern in Malaysian public hospitals from 2010 to 2016 found that 51.8% of patients who received a painkiller prescription were given one of the NSAIDs. NSAIDs are popular in community pharmacies too. A study on 25 community pharmacies in Malaysia found that 49% of visiting customers requested for an NSAID by name. 

For a class of drugs that is so widely prescribed and used, you may be surprised to find that many NSAIDs users do not know its side effects, especially if taking it for a long-term basis.

Know your NSAIDs

NSAIDs is a large class of medications, but it can be grossly classified into two types: nonselective NSAIDs and selective COX-2 inhibitors (or coxibs). You may not know what ‘COX-2’ is but we will explain that in a minute. Just remember that for now, there are nonselective NSAIDs and selective NSAIDs.

Examples of nonselective NSAIDs:

• Aspirin (e.g. Cardiprin^®)

• Ibuprofen (e.g. Nurofen^®)

• Naproxen (e.g. Synflex^®)

• Diclofenac (e.g. Voren^®, Remafen^®)

• Mefenamic acid (e.g. Ponstan^®)

• Meloxicam (e.g. Mobic^®)

Examples of selective COX-2 inhibitors:

• Celecoxib (Celebrex^®)

• Etoricoxib (Arcoxia^®)

Okay, now we’re about to get into the hard science here.

The COX Pathway

Image credit: https://www.sciencedirect.com/science/article/pii/S2211913215300620. Under a Creative Commons license (CC BY-NC-ND 4.0)

This figure shows a COX pathway of arachidonic acid. For instance, when your body tissues are injured, this pathway will be stimulated to release a series of prostaglandins, annotated as the ‘PG’ at the lowest level (PGE2, PGI2, PGD2 etc.). These prostaglandins have their virtues: they protect the kidney, keep blood pressure at a healthy level, and maintain the coating in your digestive tract. Just one downside – their presence can also bring about inflammation and pain. 

The production of prostaglandins is made possible by two important actors: COX-1 and COX-2. Both of them are ‘brothers’, yet they have important differences in how they work in the body. COX-1 is described as a "housekeeping" enzyme  – it regulates normal cellular processes (such as gastric protection, blood circulation, platelet aggregation, and kidney function). The benefits of prostaglandins can be largely attributed to COX-1. In short, COX-1 is good and you would want to keep it. On the other hand, scientists learned that COX-2 is increased when your body tissues are injured and inflamed. Individuals with diseases such as diabetic kidney disease, high blood pressure, bone fracture, and heart failure also have high levels of COX-2. You can say that the nasty effects of prostaglandins are attributed to COX-2. COX-2 is linked to inflammation and pain, and you want it to go away. 

Basically COX-1 and COX-2 are like Thor and Loki.

Now we have established the roles of COX-1 and COX-2, it is easy to explain how NSAIDs work. In general, NSAIDs reduce the production of prostaglandins by blocking COX-1 and/or COX-2, thereby reducing pain and inflammation. Nonselective NSAIDs block both COX-1 and COX-2, because well, they are nonselective. As a result, nonselective NSAIDs also eliminate many advantages of COX-1, such as gastric protection, which leads to gastric side effects seen in nonselective NSAIDs users. On the contrary, coxibs only block COX-2, that is why they have lesser gastric side effects compared to nonselective NSAIDs. Coxibs sound like a better choice here, especially for people with gastric issues. However, they are not cheap. 

For example, a strip of generic mefenamic acid costs about RM3-RM4. Whereas a strip of Arcoxia® can easily cost anywhere between RM35 to RM70. 

‘Poking holes’ in your digestive tracts

When you take nonselective NSAID, it blocks the COX-1 enzyme that protects the lining of your digestive tract. Therefore, gastric pain is a common side effect associated with nonselective NSAID. It can even lead to gastrointestinal bleeding or perforation due to gastric ulcer if taking it for a long period of time. A meta analysis has established that users of nonselective NSAIDs are at approximately three times greater relative risk for developing serious gastrointestinal side effects than are nonusers. 

BruceBlaus, CC BY-SA 4.0 , via Wikimedia Commons

The risk of gastrointestinal bleeding due to nonselective NSAIDs is even greater in the following scenario:

• Users have an existing gastrointestinal disease such as dyspepsia/indigestion, gastric ulcer, H.pylori infection etc.

• Elderly

• Users are using other medications that may harm the digestive tract concurrently, such as steroids, anticoagulants/blood thinner, clopidogrel (for heart diseases) and, possibly, bisphosphonates (for osteoporosis) and selective serotonin reuptake inhibitors (for depression and psychiatric illness). 

On the other hand, many clinical trials have confirmed that coxibs have lower risk of gastric side effects when compared to nonselective NSAIDs. If you experience any gastric side effects when taking nonselective NSAIDs, let your doctor know. Your doctor may add in a gastric medication for you, or he or she might switch you to a coxibs. 

In Part 2, we will talk about how taking NSAIDs long-term may affect your kidney, blood pressure, heart and more. Stay tuned!

Written by

Ms Joyce Toh