NSAIDs in the Management of Rheumatoid Arthritis

Overview

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first drugs used to symptomatically treat RA.[1] While they are not as potent anti-inflammatory drugs as glucocorticoids, they tend to have fewer side effects and offer pain relief.[2][3] In addition, they may later be combined with DMARDs to control the disease process.[4] The NSAIDs focused on below are ibuprofen, diclofenac, and celecoxib.

Pharmacokinetics

NSAIDS exert their effects by inhibiting the COX-1 and COX-2 forms of enzymes that synthesize prostaglandins.[5] Inhibition of COX-1 blocks the production of beneficial and protective prostaglandins, whereas inhibition of COX-2 blocks the synthesis of prostaglandins in inflamed tissues. Ibuprofen and diclofenac block both forms of the enzyme (Roberts & Morrow, 2001).[6] Celecoxib, on the other hand, selectively inhibits only COX-2.[5]

To determine which NSAID should be prescribed, the pharmacokinetics of the drugs should be considered. The half-lives of NSAIDs vary, ranging from a couple of hours (ibuprofen and diclofenac) to eleven hours (celecoxib). Absorption methods also differ. Ibuprofen is primarily absorbed by the GI tract and diclofenac undergoes first-pass metabolism via the liver, resulting in 50% bioavailability. The exact absorption mechanism for celecoxib is still unknown. All three undergo metabolism via the liver and are typically excreted in urine.[7][8][9]

Clinical Implications

NSAIDs have relatively low side effects, but potential adverse effects should still be considered. Because most NSAIDs are non-selective for COX-1 and COX-2, ibuprofen and diclofenac can cause GI bleeding. Conversely, the selectivity of celecoxib may lead to cardiovascular problems. In either case, edema, exfoliative dermatitis, Stevens-Johnson Syndrome, and renal failure may occur. Physical therapists and other clinicians treating patients with RA should be cognizant of these side effects and monitor for appearance of related symptoms. Dizziness, heart rate, and weakness can affect gait and functional activities. Expecting mothers and those with a history of cardiovascular disease or diabetes should consult their physician prior to use of these medications.[7][8][9]

References

  1. O'Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med. 2004;350(25):2591-2602.
  2. Gotzche PC, Johansen HK. Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory drugs in rheumatoid arthritis. Cochrane Databse Syst Rev. 2004;(3):CD000189. doi:10.1002/14651858.CD000189.pub2
  3. Adebajo A. Non-steroidal anti-inflammatory drugs for the treatment of pain and immobility-associated osteoarthritis: consensus guidance for primary care. BMC Fam Pract. 2012;13:23. doi:10.1186/1471-2296-13-23.
  4. Blumenauer B, Cranney A, Clinch J, Tugwell P. Quality of life in patients with rheumatoid arthritis: which drugs might make a difference. Pharmacoeconomics. 2003;21(13):927-940.
  5. 5.0 5.1 Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res. 2003;110(5-6):255-258.
  6. Roberts LJ, Morrow JD. Analgesic-antipyretic and antiinflammatory agents and drugs employed in the treatment of gout. In: Hardman JG et al, ed. The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill;2001.
  7. 7.0 7.1 U.S. Food and Drug Administration. Motrin® Ibuprofen Tablets, USP. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017463s105lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.
  8. 8.0 8.1 U.S. Food and Drug Administration. Voltaren® (diclofenac sodium enteric-coated tablets). https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019201s046lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.
  9. 9.0 9.1 U.S. Food and Drug Administration. Celebrex® celecoxib capsules. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020998s026lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.
<<Back to Pharmacological Management of Rheumatoid Arthritis