Nonsteroidal Antiinflammatory Drugs

Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Common side effects include GI irritation, prolonged bleeding, and AKI.

Last update:

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp


Mechanism of action

Nonsteroidal antiinflammatory drugs (NSAIDs) exert their therapeutic effects by interrupting fatty acid metabolism, primarily the action of cyclooxygenase (COX) on arachidonic acid (AA). 

  •  Arachidonic acid is a phospholipid found in cell membranes that is released by a variety of stimuli to include cell membrane damage.
  • COX converts arachidonic acid into: 
    • Thromboxanes: 
      • Involved in platelet adhesion
      • Involved in vasoconstriction
    • Prostaglandins:
      • Mediate inflammation
      • Increase hypothalamic temperature set-point
      • Involved in anti-nociception
      • Trigger uterine contractions during menstruation
    • Prostacyclin (prostaglandin I2): 
      • Inhibits platelet aggregation
      • Involved in vasodilation
  • There are 2 COX isoenzymes:
    • COX-1 is constitutively expressed in the body:
      • Involved in maintenance of GI mucosal lining
      • Involved in kidney vasoregulation
      • Involved in platelet aggregation
    • COX-2–induced expression occurs only during the inflammatory response 
  • Non–COX-selective NSAIDs:
    • Irreversibly (aspirin) or reversibly (other NSAIDs) inhibit both COX-1 and COX-2 
    • Decrease synthesis of: 
      • Thromboxane A2 (TXA2)
      • Prostaglandins
      • Prostacyclins
    • Therapeutic and adverse effects are attributed to diminution of these eicosanoids
  • COX-2–selective NSAIDs:
    • Selectively inhibit COX-2
    • Decrease prostaglandin synthesis 
    • Spare COX-1 and, therefore, TXA2 synthesis
    • Have different side effect profiles from nonselective NSAIDs


NSAIDs are generally very similar:

  • Lipid-soluble weak acids
  • Nearly complete absorption from GI tract
    • Topical formulations are available (diclofenac)
    • IV formulations are available (ibuprofen)
  • Minimal 1st-pass hepatic metabolism
  • Highly protein-bound 
  • Small volume of distribution
  • Metabolized by CYP3A and CYP2C and /or glucuronidation.
  • Half-lives vary from < 2 to > 8 hours.
  • Excreted renally
Arachidonic acid pathway Nonsteroidal anti-inflammatory drugs

Arachidonic acid pathway
HPETEs: hydroperoxyeicosatetraenoic acids
LOX: lipoxygenase
LT: leukotriene

Image by Lecturio. License: CC BY-NC-SA 4.0


NSAIDs can be divided into groups based on their ability to inhibit the isoforms of cyclooxygenase (COX-1 and COX-2).

  • Nonselective NSAIDs inhibit both COX-1 and COX-2.
    • Included in this category: 
      • Aspirin
      • Diclofenac
      • Ibuprofen
      • Naproxen
      • Mefenamic acid
      • Indomethacin
      • Ketoprofen
      • Piroxicam
      • Sulindac
  • Selective NSAIDs inhibit only the COX-2 isoform.
    • Included in this category:
      • Celecoxib
      • Meloxicam (at doses < 7.5 mg/day)


  • Aspirin:
    • Low dose (< 300 mg/day): antiplatelet effect to prevent atherosclerotic ischemic events
    • Medium dose (300–2400 mg/day): analgesic and antipyretic effects
    • High dose (2400–4000 mg/day): antiinflammatory effect
  • Reversible NSAIDs:
    • Analgesic
    • Antipyretic
    • Antiinflammatory
    • Closure of patent ductus arteriosus (indomethacin)
  • Celecoxib:
    • Rheumatoid arthritis
    • Osteoarthritis

Related videos

Adverse Effects

GI tract effects

  • Prostaglandins inhibit gastric acid secretion and promote protective mucus production. 
  • NSAIDs block prostaglandins:
    • → Dyspepsia
    • → GI erosion
    • → GI ulceration
    • → GI bleeding

Cardiovascular effects

  • Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation.
  • NSAIDs block prostacyclin:
    • → Vasoconstriction
    • → Platelet aggregation
  • Platelets contain only COX-1, which produces TXA2.
  • Thromboxane A2 is a potent vasoconstrictor and platelet aggregator and is thrombogenic.
  • Selective COX-2 inhibition results in unopposed COX-1 effects:
    • → Vasoconstriction
    • → Platelet aggregation
    • → Prothrombotic state
  • Long-term COX-2 inhibitor use is associated with increased risk of cardiovascular complications. 
  • Nonselective NSAIDs (except aspirin) also are associated with increased risk (though less than with selective COX-2). 
  • Safest NSAID/cardiovascular risk profile in this setting appears to be naproxen.

Renal effects

  • Prostaglandins are involved in renin release, regulation of vascular tone, and control of tubular function in the kidneys.
  • NSAIDs block prostaglandins:
    • → AKI
    • → Interstitial nephritis
    • → Renal papillary necrosis

Miscellaneous effects

  • NSAID-associated bleeding risk significant only in combination with other anticoagulants.
  • Diclofenac and sulindac have been associated with liver dysfunction and failure.

Aspirin Toxicity

Salicylate toxicity is a series of symptoms and metabolic disturbances attributable to excessive ingestion of salicylic acid (e.g., aspirin and other over-the-counter (OTC) preparations). Accidental exposure is seen in pediatric patients, whereas purposeful exposure is more commonly observed in adolescents and young adults (i.e., suicide attempt).

  • Initial symptoms:
    • Nausea and vomiting
    • Tinnitus and vertigo (cranial nerve (CN) VII overactivation)
    • Diaphoresis
    • Hyperventilation
    • Tachycardia
    • Hyperactivity 
  • Symptoms of progressive toxicity:
    • Agitation
    • Delirium
    • Convulsions
    • Lethargy/stupor
    • Hyperthermia
  • Metabolic (acid–base) disturbance:
    • The early phase of respiratory alkalosis: due to the overactivation of the medullary respiratory center
    • The middle phase of combined respiratory alkalosis and metabolic acidosis
    • The late phase of high anion gap metabolic acidosis: due to aspirin metabolite (salicylate)
  • Treatment:
    • Aspirin toxicity treated with sodium bicarbonate (NaHCO3): sodium bicarbonate alkalinizes urine, facilitating salicylate excretion.
    • Dialysis may be needed if sodium bicarbonate treatment is unsuccessful.

Related videos

Comparison of NSAIDs

Table: Comparison of NSAIDs
ClassMechanism of actionClinical useSide effects
Reversible NSAIDs (e.g., ibuprofen, ketorolac, indomethacin)
  • Reversibly inhibit COX-1 and COX-2
  • Decreased prostaglandin and thromboxane A2 (TXA2) synthesis
  • Analgesic
  • Antipyretic
  • Antiinflammatory
  • Closure of patent ductus arteriosus (PDA)
  • Gastric ulcers and GI bleeding
  • AKI
  • Interstitial nephritis
  • Renal papillary necrosis
  • Aspirin:
    • Reye syndrome in children with a viral infection
    • Asthma-like symptoms in patients with nasal polyps or atopy
    • Tinnitus
    • Mixed respiratory alkalosis–metabolic acidosis
  • Irreversibly inhibits COX-1 and COX-2
  • Decreased prostaglandin and TXA2 synthesis
  • Low dose (< 300 mg/day): antiplatelet
  • Medium dose (300–2400 mg/day): analgesic and antipyretic
  • High dose (2400–4000 mg/day): antiinflammatory
COX-2 inhibitors (e.g., celecoxib)
  • Selectively inhibit COX-2
  • Decreased prostaglandin synthesis
  • Spared platelets and TXA2 synthesis
  • Rheumatoid arthritis
  • Osteoarthritis
  • Increased risk of thrombosis:
    • Deep venous thrombosis
    • Pulmonary embolism
  • Acute MI
  • Sulfa allergy


  1. Solomon, D.H. (2020). Nonselective NSAIDs: overview of adverse effects. UpToDate. Retrieved June 20, 2021, from
  2. Solomon, D.H. (2019). NSAIDs: pharmacology and mechanism of action. UpToDate. Retrieved June 20, 2021, from
  3. Solomon, D.H. (2021). Overview of COX-2 selective NSAIDs. UpToDate. Retrieved June 20, 2021, from
  4. Phillips, W.J., Currier, B.L. (2004). Analgesic pharmacology: II. Specific analgesics. J Am Acad Orthop Surg 12:221–233.
  5. Dawood, M.Y. (2006). Primary dysmenorrhea: advances in pathogenesis and management. Obstet Gynecol 108:428–441.
  6. Shekelle, P.G., et al. (2017). Management of gout: a systematic review in support of an American College of Physicians clinical practice guideline. Ann Intern Med 166:37–51.
  7. Oyler, D.R., et al. (2015). Nonopioid management of acute pain associated with trauma: Focus on pharmacologic options. J Trauma Acute Care Surg 79:475–483.
  8. Zacher, J., et al. (2008). Topical diclofenac and its role in pain and inflammation: an evidence-based review. Curr Med Res Opin 24:925–950.
  9. Van den Bekerom, M.P.J., et al. (2015). Non-steroidal anti-inflammatory drugs (NSAIDs) for treating acute ankle sprains in adults: benefits outweigh adverse events. Knee Surg Sports Traumatol Arthrosc 23:2390–2399.
  10. May, J.J., Lovell, G., Hopkins, W.G. (2007). Effectiveness of 1% diclofenac gel in the treatment of wrist extensor tenosynovitis in long distance kayakers. J Sci Med Sport 10:59–65.
  11. Barkin, R.L. (2015). Topical nonsteroidal anti-inflammatory drugs: the importance of drug, delivery, and therapeutic outcome. Am J Ther 22:388–407.
  12. Vane, J.R. (1971). Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 231:232–235.
  13. Chaiamnuay, S., Allison, J.J., Curtis, J.R. (2006). Risks versus benefits of cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs. Am J Health Syst Pharm 63:1837–1851.
  14. Day, R.O., Graham, G.G. (2013). Nonsteroidal anti-inflammatory drugs (NSAIDs). 346:f3195.

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.