Ibuprofen: The Metabolic Processes for Pain Relief

Ibuprofen, commonly known by its brand name Advil, is the most commonly used non-steroidal anti-inflammatory drug (NSAID) for both chronic and acute pain relief. Likely having used it yourself for a headache, fever, or after a medical procedure, it is worth examining exactly how Ibuprofen came to be and its chemical basis for pain relief. 

Initial Discovery

Ibuprofen is a derivative of propionic acid and was initially discovered as an alternative to Aspirin by the Boots Group, a UK based pharmaceutical group. Although initially used in treatment of rheumatoid arthritis, a disease resulting in the painful swelling of joints, ibuprofen would later become the second, following Aspirin, over-the-counter NSAID.

NSAID stands for non-steroidal anti-inflammatory drug. While the term “steroid” is commonly associated with bodybuilding and sports, in this context, steroid refers to corticosteroids. Corticosteroids are synthetic hormones that, in a medical setting, are used to reduce inflammation and are highly effective. Steroids work by suppressing the response of the immune system to an injury. In suppressing an immune system response, like swelling, less pain is felt. While steroids generally tend to be more effective than non-steroidal counterparts, they come with a variety of consequences. Due to increased potency, steroids can come with a variety of side effects such as weight gain, blurred vision, acne, and difficulty sleeping. Steroids are only given by prescription in the United States and doctors primarily use them when non-steroidal therapeutic treatments are not working. NSAIDs work in a very similar manner to steroids but the major difference is that NSAIDs do not suppress the immune system.

How Ibuprofen works in the body

One advantage of using NSAIDs is that there is no immunosuppressive effect. Ibuprofen works by inhibiting the production of Prostaglandins. Prostaglandins are a group of compounds that contribute to inflammatory response and perform signaling of symptoms such as fever and pain. Different prostaglandins have different roles within the body. Some regulate temperature while others regulate sleep and some are even responsible for the symptoms of allergic reactions. The first step in understanding Ibuprofen and its mechanism within the body is to acknowledge phospholipase A2. Phospholipase A2 is an enzyme released following injury or tissue irritation. Phospholipase A2 converts phospholipids within the cell membrane into Arachidonic Acid. Prostaglandins are produced from Arachidonic Acid by COX enzymes 1 and 2. COX-1 is naturally occurring in most cells and is the primary physiological source for prostaglandins. COX-2 on the other hand is primarily a result of induction from inflammatory stimuli and is the principal source for inflammatory prostaglandins. NSAIDs can be placed upon a spectrum of selectivity where some are more specific in inhibiting COX-2 whereas other, non-selective NSAIDs inhibit COX-1 and COX-2. Ibuprofen lies relatively in the middle of the spectra, inhibiting both COX-1 and COX-2. 

• Aspirin, like Ibuprofen, is a common NSAID. What is special about Aspirin is that, unlike non-selective NSAIDs, Aspirin works as an irreversible inhibitor. Normally, non-selective NSAIDs compete with Arachidonic Acid to bind to the COX enzyme. Aspirin permanently changes the COX enzyme in a way that is irreversible and results in less competition from Arachidonic Acid. Platelets in the blood, responsible for forming clots and stopping bleeding are heavily impacted by Aspirin as no new platelets can be formed when COX is inhibited. This is the reason that Aspirin is sometimes prescribed to reduce the likelihood of a blood clot forming in order to prevent heart attacks and ischemic strokes.

While the inhibition of COX-1 and COX-2 is great for pain relief, there are possible consequences. COX-1 is responsible for producing prostaglandins that form the gastric mucosal barrier. The gastric mucosal barrier is responsible for providing a layer of protection to the stomach and preventing the gastric acid from damaging the organ itself. Inhibition of COX-1 prevents this process from occurring as detailed in the diagram below. These side effects are rare and usually only occur after heavy dosing for an extended period of time.

Common Alternatives to Ibuprofen

When people think of pain relief, in addition to Ibuprofen another drug usually comes to mind- Acetaminophen. Commonly known by its brand name Tylenol, Acetaminophen, despite working to relieve pain, is not an NSAID and does not reduce inflammation within the body. Acetaminophen is metabolized through the same pathway and acts as a COX inhibitor in the same way that Ibuprofen does. The major difference comes in that Acetaminophen is only active within the central nervous system whereas Ibuprofen acts in the central nervous system and throughout the whole body. Acetaminophen targets an area of your brain responsible for heat regulation which results in a reduction of fever. Acetaminophen, in combination with aspirin, and caffeine, is also commonly used to treat migraines. In this combination, caffeine, a stimulant (read about here), helps to increase the effects of aspirin and acetaminophen. Aspirin, as noted previously in the article, is an NSAID that helps to reduce inflammation. One can infer that this combination of acetaminophen, aspirin, and caffeine is an effective way to reduce multiple types of pain and inflammation throughout the body rapidly and effectively.

Commonly known and used, Ibuprofen has become a staple in over-the-counter pain relief. With millions of Americans, and many millions more worldwide, consuming Ibuprofen daily, the $1.43 billion market won’t disappear anytime soon. Although effective for pain relief, one should consult a physician or other trusted healthcare provider to avoid adverse effects and drug-drug interactions that could occur within the body.

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