Nonsteroidal Anti-inflammatory Drugs
Clinicians use a wide variety of NSAIDs to treat RA and other rheumatic diseases. These agents decrease synthesis of inflammatory mediators such as prostaglandins by inhibiting the enzyme cyclooxygenase (COX), and all are analgesic, antipyretic, and anti-inflammatory. The COX enzyme has 2 isoforms. COX-1 is present in most cells and appears to be involved in various aspects of cellular metabolism, such as gastric cytoprotection, platelet aggregation, and renal function. COX-2 is present in some tissues, including brain and bone, but is also expressed at other sites in response to inflammation.
Complications from the use of oral NSAIDs account for approximately 12% of hospital admissions and more than 16,000 deaths each year in the United States. Their most significant adverse effects include gastrointestinal bleeding, renal failure, hypertension, and heart failure, as well as induction of asthma in aspirin-sensitive individuals. Oral NSAIDs can also interfere with platelet function and can cause bone marrow suppression, hepatic toxicity, and CNS symptoms including headache, dizziness, and confusion. In rare cases, NSAIDs have been associated with ocular adverse effects such as nonspecific blurred vision and diplopia. There have also been reports of possible optic neuropathy and macular edema, especially with use of ibuprofen.
The traditional NSAIDs inhibit both isoforms of COX. Selective COX-2 inhibitors have a lower risk of gastrointestinal damage and have less effect on platelet function. Two of these drugs (rofecoxib and valdecoxib) have been removed from the market worldwide because of adverse cardiovascular events. However, parecoxib, a prodrug of valdecoxib, remains available in many European countries. Similar concerns have been raised about celecoxib; although it is still available, this drug carries significant warnings. It has been proposed that the selective blocking of COX-2 decreases the production of prostacyclins, which cause vasodilation and inhibit platelet aggregation, leading to increased prothrombotic activity. Etoricoxib, another COX-2–selective NSAID, is available outside the United States. Ophthalmologists should be aware that conjunctivitis, temporary blindness, and blurred vision have been reported with use of COX-2 inhibitors.
Systemic NSAIDs may be useful in helping to control uveitis or scleritis in some patients, but they are not as effective as corticosteroids. Several topical NSAIDs have been approved for ocular use; they are discussed in BCSC Section 8, External Disease and Cornea, and Section 9, Uveitis and Ocular Inflammation.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.