IBUPROFEN: The Triple Treat For Sick Kids

Imagine your two year old child is having severe toothache or a debilitating head ache. Your 5 year old daughter has a swelling with pain in her neck due to an enlarged lymph node (or kulani). Your 7 year old son has high grade fever of two days’ duration…

What can you do? Should you go to your doctor soonest? What can you give these children to relieve their symptoms?

Of course, the most logical thing to do is immediately see your friendly pediatrician or family doctor to consult what is really happening to your child so a definitive management can be instituted the soonest possible time. However, for the meantime, you might want to give him or her something to relieve the symptom temporarily (or even permanently) so the child can be more comfortable or even become symptom-free in the long run.

And what can that remedy be? Ibuprofen may be your best bet.

Basically, ibuprofen is an non-steroidal anti-inflammatory agent. It works by reducing hormones that cause inflammation and pain in the body. It can be a pain reliever, a fever reducing agent or an anti-inflammatory drug. Pain, fever and symptoms of inflammation like redness, swelling and pain can all occur when the body releases chemicals called prostaglandins.

Ibuprofen is a non-selective inhibitor of an enzyme called cyclooxygenase (COX), which is required for the synthesis of prostaglandins via the arachidonic acid pathway. COX is needed to convert arachidonic acid to prostaglandin H2 (PGH2) in the body. PGH2 is then converted to prostaglandins. The inhibition of COX by ibuprofen, therefore, lowers the level of prostaglandins made by the body, hence the symptom (whether pain, swelling or fever) may also be reduced or eliminated.

The prostaglandins that are formed from PGH2 are important mediators of sensations, such as pain, fever and inflammation. The antipyretic effects of ibuprofen may arise as a result of its action on the hypothalamus that subsequently leads to vasodilation, an increased peripheral blood flow, and subsequent heat dissipation.

The anticoagulant effects of ibuprofen are also mediated through inhibition of COX, which converts arachidonic acid into thromboxane A2, a vital component in platelet aggregation that leads to the formation of blood clots.

There are two forms of COX in the body, which include COX-1 and COX-2. The pain and inflammation-reducing effects of NSAIDs are mediated through the inhibition of COX-2, whereas COX-1 inhibition blocks the formation of thromboxane.

The initial and immediate effect of ibuprofen is a reduction in pain. The anti-inflammatory actions may be gradual in occurrence.

Taking the appropriate dose of ibuprofen can ensure that positive health effects, such as reduced pain, inflammation, and fever, outweigh any possible negative effects of the drug, such as gut irritation or bleeding. The difference in dose between the amount that causes positive health effects and the amount that causes adverse effects is referred to as the therapeutic window.

Ibuprofen may come in tablets, capsules, suppositories but for children a kid-friendly syrup preparation is also available.

Ibuprofen works on one of the body’s chemical pathways for pain. It reduces your body’s ability to make prostaglandins which are the natural chemicals that trigger pain.

With fewer prostaglandins in your body, pain is reduced. However, it does not exactly cure the cause of the pain, therefore, consulting your doctor to diagnose the cause of the pain is still mandatory.

Ibuprofen also works for fever. The mechanism also involves antagonizing prostaglandin which can increase your body temperature and also via its direct on the hypothalamus in your brain.

In 1998, we made a meta-analysis to determine if paracetamol is as good or even better than ibuprofen in lowering down the body temperature. Our results revealed that for the temperature monitoring, a total of 454 patients from 7 studies were included. Ibuprofen had a greater reduction in temperature as compared to paracetamol. Ibuprofen lowered down the fever 15 to 30 minutes faster and earlier than paracetamol 1,2,4,6 and 8 hours after intake and they were all statistically significant. The overall side effects were similar between the two drugs. The side effects were based on the observation of a total of 84,844 patients from ten studies. Our meta-analysis therefore concluded that ibuprofen as compared to paracetamol produced:

The results also showed that ibuprofen had similar incidence of overall side effects as compared to paracetamol.

In a more recent meta-analysis (2022) 10 studies were included with a total of 1773 patients. The results showed that acetaminophen had higher temperature than ibuprofen after 1 hour, 2 hours and 4 hours. There is no difference between two drugs in the adverse events. Thus, again this study suggested that ibuprofen is more effective than acetaminophen in children with infectious fever.

However, caution should be mentioned here regarding its use in proven dengue patients.

Pain was also studied with regard the use of ibuprofen. In 2010, a paper was done with 6 eligible studies that included efficacy and/or safety data (adverse events) in a direct comparison of ibuprofen with acetaminophen for treatment of pain in children.

In those studies majority of them reported that ibuprofen was superior to acetaminophen and one study found a significant difference for ibuprofen only on the day of surgery and not at later time points. In the meta-analysis of RCTs, ibuprofen was associated with a significantly lower pain score than acetaminophen at two hours post dose. Again, no difference was seen in terms of adverse events between the two drugs.

This was validated in a more recent meta-analysis (2020) wherein ibuprofen was noted to have less pain at 4 to 24 hours.

Given its anti-inflammatory activity, ibuprofen is the treatment of choice for pain with an inflammatory component, like in arthritis. Ibuprofen reduced the duration of symptoms, without causing serious adverse events among children with synovitis. Indeed, although the disorder resolved within 7 days in 80% of the patients of both groups, the mean duration of symptoms was shorter in the group treated with ibuprofen (2 days) than in that receiving placebo (4.5 days).

Overall, ibuprofen is confirmed as the drug of first choice in the treatment of inflammatory pain in children.