|MadSci Network: Medicine|
Great question! In your question, you pointed out one of the major differences between ibuprofen (one member of a class of drugs referred to as nonsteroidal anti-inflammatory drugs, or NSAIDs, for short) and acetaminophen. This important difference is that ibuprofen has anti-inflammatory effects while acetaminophen does not. Both of these drugs are pain relievers, or analgesics. However, with musculoskeletal injuries, there frequently is inflammation in the injured area, as well as pain. Relieving pain is obviously of extreme importance, but reducing inflammation is a priority as well. Inflammation can result in tissue damage and can also cause pain. Thus, the primary reason why you instructed injured athletes to treat their themselves with ibuprofen and not acetaminophen is to reduce inflammation while also relieving pain.
Acute inflammation and the action of prostaglandins
So, why do these drugs have different effects? Well, to answer that question I should first tell you a little bit about inflammation. Specifically, I will discuss acute inflammation, which is the initial response to tissue injury (such as an ankle sprain). There is also chronic inflammation, often associated with diseases such as rheumatoid arthritis, that occurs with a different time course and involves different cellular and chemical mediators than the acute variety. During the acute inflammation that results following an injury, blood flow to the affected area increases as a result of vessel dilatation. Not only do the blood vessels dilate, they become leaky, allowing proteins from the blood to spill out of the vessels and into the surrounding tissues. Grossly, the effects of this leakiness are observed as swelling or edema near the site of injury. White blood cells, or leukocytes, are heralded to the site of injury (a process referred to as chemotaxis), traveling first in the bloodstream and then, leaving the circulation by migrating through vessel walls. Leukocytes are the major effectors of inflammation. During an infection, they are capable of engulfing microbes using a process known as phagocytosis. In addition, they are capable of releasing a host of chemicals that can damage tissues. One family of chemicals that leukocytes, as well as some other cell types, release during acute inflammation is called prostaglandins. Prostaglandins are synthesized in and released from the leukocytes. In general, prostaglandins function to dilate blood vessels and promote leakiness. To make prostaglandins, leukocytes use a compound known as arachidonic acid as a starting material, and convert it into prostaglandins through the action of an enzyme called cyclooxygenase. NSAIDs, including aspirin and ibuprofen, work by inhibiting cyclooxygenase activity, thus reducing prostaglandin synthesis. With less prostaglandins around, there is less inflammation.
The problem with NSAIDs…and a possible solution
This is the basic premise behind treating sports injuries with an NSAID such as ibuprofen--reduce pain, but more importantly, reduce inflammation by interfering with prostaglandin synthesis. Until now, I have mainly emphasized the role of prostaglandins as mediators of inflammation. However, prostaglandins do many other things: they help protect the lining of the gut; they keep platelets, which are important for blood clotting, working properly; and they help maintain normal kidney function, to name just a few of their attributes. Unfortunately, NSAIDs interfere with these prostaglandin-mediated activities as well. In fact, many of the undesirable side effects of NSAIDs (for example, gastrointestinal irritation and impaired blood clotting) are due to reductions in these "good" functions of prostaglandins. One of the exciting developments in this field is the discovery that there are actually two forms of cyclooxygenase, the enzyme that makes prostaglandins. Cyclooxygenase-1 (or, COX-1) is responsible for making the "good" prostaglandins--that is, mainly those not involved in inflammation, while cyclooxygenase-2 (or, COX- 2) is the major producer of "inflammatory" prostaglandins. NSAIDs inhibit the functions of both COX-1 and COX-2, leading to a reduction in inflammation as well as a host of nasty side effects. The ideal analgesic/ anti-inflammatory agent would be one that could interfere with COX-2 function while leaving COX-1 function intact. A number of pharmaceutical companies have been pursuing this problem and now, two COX-2 inhibitors are available. These two drugs, known by their trade names Celebrex and Vioxx, are currently available only by prescription and are approved for a limited number of indications, such as rheumatoid arthritis. The development of drugs that are able to specifically inhibit COX-2 and relieve pain and inflammation, while producing few of the side effects typical of more "primitive" NSAIDs is especially exciting. Perhaps a more widely available, over-the-counter COX-2 inhibitor is not so far away…
I hope you find this information helpful. If you have any further questions, feel free to contact me. For a general reference on tissue injury and inflammation, I suggest the pathology textbook, Robbins Pathologic Basis of Disease, 6th edition, by Ramzi S. Cotran, Vinay Kumar, Tucker Collins, and Stanley L. Robbins.
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