Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

  • Karina GritsenkoEmail author


Nonsteroidal anti-inflammatory drugs, NSAIDs, have a substantial role in medical practice. They are commonly acquired as over-the-counter medications but may also be prescribed for their ability to relieve pain, alleviate inflammation, and reduce fever. NSAIDs work by inhibition of the cyclooxygenase enzymes (COX), affecting the production of mediators involved in pain pathways and inflammation. NSAIDs have become well known for a multitude of adverse effects, which stem from altering the homeostatic properties of cyclooxygenase in various organs. In an attempt to mitigate some of the adverse effects, COX-2 selective medications were introduced; however, there still remain undesired reactions and potential harm from their use.

Note: Although acetaminophen is not an NSAID, it is typically discussed alongside these compounds. In this text, acetaminophen is covered in the Cancer Pain chapter.


Pain Analgesia COX-1 COX-2 NSAIDs Prostaglandins Inflammation Side effects 


  1. 1.
    Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986–1000. Scholar
  2. 2.
    Smyth EM, Grosser T, Wang M, Yu Y, FitzGerald GA. Prostanoids in health and disease. J Lipid Res. 2009;50:S423–8.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem. 2000;69:145–82.CrossRefPubMedGoogle Scholar
  4. 4.
    Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE. Cyclooxygenase in biology and disease. FASEB J. 1998;12:1063–73.CrossRefPubMedGoogle Scholar
  5. 5.
    Rouzer CA, Marnett LJ. Cyclooxygenases: structural and functional insights. J Lipid Res. 2009;50(Suppl):S29–34. Scholar
  6. 6.
    Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294:1871–5.CrossRefPubMedGoogle Scholar
  7. 7.
    The thromboxane/endoperoxide receptor (TP): the common villain, Nakahata N. Thromboxane A2: physiology/pathophysiology, cellular signal transduction and pharmacology. Pharmacol Ther. 2008;118:18–35.CrossRefGoogle Scholar
  8. 8.
    Mehanna AS. NSAIDs: chemistry and pharmacological actions. Am J Pharm Educ. 2003;67(2):Article 63. Scholar
  9. 9.
    Meade EA, Smith WL, DeWitt DL. Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J Biol Chem. 1993;268:6610–4.PubMedGoogle Scholar
  10. 10.
    Blobaum AL, Lawrence J, Marnett J. Structural and functional basis of cyclooxygenase inhibition. Med Chem. 2007;50(7):1425–41. Publication Date. March 7, 2007. Copyright 2007 American Chemical Society.CrossRefGoogle Scholar
  11. 11.
    Katzung & Trevor’s pharmacology: examination & board review 11e. Chapter 36: NSAIDs, Acetaminophen, & Drugs Used in Rheumatoid Arthritis & Gout. Copyright © 2015, 2013, 2010, 2008, 2005, 2002 by McGraw-Hill Education. All rights reserved. Printed in the United States of America.Google Scholar
  12. 12.
    Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors. Steven D. Waldman. Pain Management, Second Edition. Chapter 121, 884–889. Copyright 2011, 2007 by Saunders, an imprint of Elsevier Inc. All rights reserved.Google Scholar
  13. 13.
    Mehta SK, Younoszai A, Pietz J, Achanti BP. Pharmacological closure of the patent ductus arteriosus. Images Paediatr Cardiol. 2003;5(1):1–15.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Yin T, Wang G, Ye T, Wangb Y. Sulindac, a non-steroidal anti-inflammatory drug, mediates breast cancer inhibition as an immune modulator. Sci Rep. 2016;6:19534. Published online 2016 Jan 18. Scholar
  15. 15.
    Davies NM, McLachlan AJ, Day RO, Williams KM. Clinical pharmacokinetics and pharmacodynamics of Celecoxib. A selective Cyclo-Oxygenase-2 inhibitor. Clin Pharmacokinet. 2000;38(3):225–42.CrossRefPubMedGoogle Scholar
  16. 16.
    Koki AT, Leahy KM, Masferrer JL. Potential utility of COX-2 inhibitors in chemoprevention and chemotherapy. Expert Opin Investig Drugs. 1999;8:1623–38.CrossRefPubMedGoogle Scholar
  17. 17.
    Davies G, Martin LA, Sacks N, Dowsett M. Cyclooxygenase-2 (COX-2), aromatase and breast cancer: a possible role for COX-2 inhibitors in breast cancer chemoprevention. Ann Oncol. 2002;13:669–78.CrossRefPubMedGoogle Scholar
  18. 18.
    Doña I, Blanca-López N, Cornejo-García JA, Torres MJ, Laguna JJ, Fernández J, et al. Characteristics of subjects experiencing hypersensitivity to non-steroidal anti-inflammatory drugs: patterns of response. Clin Exp Allergy. 2011;41:86–95.CrossRefPubMedGoogle Scholar
  19. 19.
    Kowalski ML, Makowska JS. Seven steps to the diagnosis of NSAIDs hypersensitivity: how to apply a new classification in real practice? Allergy Asthma Immunol Res. 2015 Jul;7(4):312–20. Published online 2015 Apr 21. Scholar
  20. 20.
    Antonucci R, Zaffanello M, Puxeddu E, Porcella A, Cuzzolin L, Pilloni MD, Fanos V. Use of non-steroidal anti-inflammatory drugs in pregnancy: impact on the fetus and newborn. Curr Drug Metab. 2012;13(4):474–90.CrossRefPubMedGoogle Scholar
  21. 21.
    Practice advisory on low-dose aspirin and prevention of preeclampsia: updated recommendations. This practice advisory was developed by the American College of Obstetricians and Gynecologists in collaboration with Christopher M. Zahn, MD; Joseph R. Wax, MD; and T. Flint Porter, MD. July 11, 2016.Google Scholar
  22. 22.
    National Reye’s Syndrome Foundation. Reye’s syndrome bulletin, 2005. Accessed 20 Aug 2009.Google Scholar
  23. 23.
    Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, Egger M, Jüni P. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086. Epub 2011 Jan 11.CrossRefGoogle Scholar
  24. 24.
    Patino FG, Olivieri J, Allison JJ, et al. Nonsteroidal antiinflammatory drug toxicity monitoring and safety practices. J Rheumatol. 2003;30(12):2680–8.PubMedGoogle Scholar
  25. 25.
    Battistella M, Mamdami MM, Juurlink DN. Risk of upper gastrointestinal Hemorrhage in Warfarin users treated with nonselective NSAIDs or COX-2 inhibitors. Arch Intern Med. 2005;165(2):189–92. Scholar
  26. 26.
    Altman RD, Perez GO, Sfakianakis GN. Interaction of cyclosporine A and nonsteroidal anti-inflammatory drugs on renal function in patients with rheumatoid arthritis. Am J Med. 1992;93(4):396–402.CrossRefPubMedGoogle Scholar
  27. 27.
    Becker DE. Adverse drug interactions. Anesth Prog. 2011;58(1):31–41. Scholar
  28. 28.
    Russell RI. Non-steroidal anti-inflammatory drugs and gastrointestinal damage---problems and solutions. Postgrad Med J. 2001;77(904):82–8.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Buttgereit F, Burmester GR, Simon LS. Gastrointestinal toxic side effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2–specific inhibitors. Am J Med. 2001;110(3):13–9.CrossRefGoogle Scholar
  30. 30.
    Sostres C, Gargallo CJ, Lanas A. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther. 2013;15(Suppl 3):S3.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Harirforoosh S, Jamali F. Renal adverse effects of nonsteroidal anti-inflammatory drugs. Expert Opin Drug Saf. 2009;8(6):669–81.CrossRefPubMedGoogle Scholar
  32. 32.
    Schlondorff D. Renal complications of nonsteroidal anti-inflammatory drugs. Kidney Int. 1993;44(3):643–53.CrossRefPubMedGoogle Scholar
  33. 33.
    Weir MR. Renal effects of nonselective NSAIDs and coxibs. Cleve Clin J Med. 2002;69(Suppl 1):SI53–8.PubMedGoogle Scholar
  34. 34.
    Bessone F. Non-steroidal anti-inflammatory drugs: what is the actual risk of liver damage? World J Gastroenterol. 2010;16(45):5651.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    García Rodríguez LA, Pérez Gutthann S, Walker AM, Lueck L. The role of non-steroidal anti-inflammatory drugs in acute liver injury. BMJ. 1992;305(6858):865–8.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Balancing Risks and Benefits: cardiovascular Safety of NSAIDs. Jul 22, 2016. Prashant Vaishnava, MD. American College of Cardiology.Google Scholar
  37. 37.
    Bally M. Risk of acute myocardial infarction with NSAIDs in real world use: Bayesian meta-analysis of individual patient data. BMJ. 2017;357:j1909. Scholar
  38. 38.
    FDA strengthens warning For NSAIDs. Jul 10, 2015 ACC News Story. American College of Cardiology.Google Scholar
  39. 39.
    Perry LA. Cardiovascular risk associated with NSAIDs and COX-2 inhibitors. US Pharm. 2014;39(3):35–8.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of AnesthesiologyMontefiore Medical Center and Albert Einstein College of MedicineBronxUSA

Personalised recommendations