Nonsteroidal Anti‐Inflammatory Drugs (NSAIDs)


Nonsteroidal anti‐inflammatory drugs (NSAIDs) constitute a very important category of drugs that has therapeutic applications exploited since centuries. NSAIDs are a key composition for pharmacological management of acute and chronic pain. These drugs have enthralling evolution from the classic molecule called aspirin to the recently available coxibs, used for treatment of inflammatory conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA). Almost all the drugs available in this category are associated with physiological side effects ranging from gastrointestinal to heart‐ and liver‐related diseases. As a result, the development and search for an ultimate magic drug molecule to treat inflammation continues to be an important face till date. The mechanism of action of NSAIDs relies mainly on inhibition of production of proinflammatory compounds by the action of cyclooxygenase (COX) enzymes. NSAIDs differ in their potency, duration of action and cause of gastric ulcer depending on their relative selectivity of COX enzymes (COX‐1/2). As recent developments, COX‐2‐selective inhibitors are being designed in search of safer and effective pain killer molecules, as COX‐1 inhibitors are associated with undesired side effects. In spite of the tremendous efforts being made since the past decade, the development of an effective and safe NSIAD to treat inflammatory conditions still presents key challenges.

Key Concepts

  • NSAIDs are most commonly used chemicals in the form of drugs.
  • Almost all NSIADs have adverse physiological effect on prolonged usage.
  • Novel category of NSAIDs to inhibit COX‐2 isoform is being developed.
  • Novel targets are needed to be explored for designing of safer drugs to control pain and inflammation.
  • More specific drugs are needed in order to avoid toxic effects.

Keywords: cyclooxygenase; inhibitor; side effects; pain killer; inflammation; eicosanoids

Figure 1. The eicosanoids production pathway.
Figure 2. Ribbon diagram showing COX‐1 (blue) and COX‐2 (cyan). The bound ligands and haem groups are also shown in ball‐and‐stick model in respective enzymes. The haem region is known as peroxidase site and NSAIDs binding site is oxygenase site in COX enzymes located distinctly in both the enzymes. The figure was drawn using Chimera (Pettersen et al., 2004).
Figure 3. Superimposition of oxygenase active site amino acids of COX‐1 and COX‐2 is shown. The amino acid residues of COX‐1 (yellow) and COX2 (cyan) are shown in ball‐and‐stick model. Val 509 in COX‐2 play crucial role for binding of coxibs. At the same position, Ile 523 creates steric hindrance with sulfonamide group of coxibs in COX‐1 active site. The Ile to Val mutation widens the NSAIDs binding cavity in COX‐2, which in turn used for designing of coxibs.


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Further Reading

Abramson S (1991) Therapy with and mechanisms of nonsteroidal anti‐inflammatory drugs. Current Opinion in Rheumatology 3 (3): 336–340.

Chandran SK (2015) Nonsteroidal anti‐inflammatory drugs (NSAIDs). In: Kimberly A Sackheim (ed) Pain Management and Palliative Care, pp. 65–69. New York, NY: Springer.

Cynthia C, Bradford B and Lara M (2014) Pharmacology of Nonsteroidal Anti‐inflammatory Drugs. Wiley Online Library. DOI: 10.1002/9781118845110.ch5

Katz JA (2005) NSAIDs and COX‐2‐selective inhibitors. In: Essentials of Pain Medicine and Regional Anesthesia, 2nd edn, pp. 141–158. Philadelphia, PA: Elsevier Churchill Livingstone.

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Kumar, Sanjit, Qamar, Imteyaz, and Singh, Nagendra(Mar 2017) Nonsteroidal Anti‐Inflammatory Drugs (NSAIDs). In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0024221]