Cyclooxygenase (COX) inhibitors

Cyclooxygenase (COX) inhibitors are non-steroidal anti-inflammatory drugs (NSAIDs), used clinically to relieve fever and pain, such as those associated with headaches, colds, flu, and arthritis. NSAIDs are available by prescription and over-the-counter (OTC).

COX inhibitors can act at one or both of the isozymes, COX-1 and COX-2.

COX-1 is involved in the synthesis of prostaglandins which are responsible for maintenance and protection of the gastrointestinal tract, whilst COX-2 produces the pro-inflammatory prostaglandins responsible for causing inflammation and pain.

Inhibitors differ in their relative specificities for COX-1 and COX-2, with examples such as aspirin, ibuprofen, naproxen and diclofenac being non-selective. Selective COX-2 inhibitors were developed to reduce the liability of gastrointestinal damage associated with COX-1 inhibition. Non-selective COX inhibitors are often prescribed with a proton pump inhibitor such as omeprazole to reduce the risk of causing gastrointestinal ulceration and bleeding. Meloxicam, valdecoxib, parecoxib and rofecoxib are examples of selective COX-2 inhibitors. However, some COX-2 selective inhibitors have been shown to cause an increased risk of heart attacks and strokes. Because of this risk all non-aspirin NSAID medications (prescription or OTC) must carry boxed warnings to alert patients to the potential danger associated with their use. The US FDA issued an updated safety warning in late 2015: FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes.