Nonsteroidal Anti-Inflammatory Drug (NSAID)

General Information

Historical Use of NSAID’s

  • 1899: Acetylsalicylic Acid (Aspirin) was the First NSAID Introduced
  • 1964: Indomethacin was Introduced
  • 1969: Ibuprofen was Introduced

Global Use of NSAID’s

  • NSAID’s are Some of the Most Commonly Used Drugs: NSAID’s account for approximately 2.5% of all pharmaceutical dollars spent globally
  • Diclofenac (Aclonac, Cataflam, Voltaren) is the Most Commonly Used NSAID Worldwide (see Diclofenac)




Acetic Acid Derivatives

  • Aceclofenac
  • Diclofenac (Aclonac, Cataflam, Voltaren) (see Diclofenac)
  • Etodolac (Lodine, Eccoxolac) (see Etodolac)
  • Indomethacin (Indocin) (see Indomethacin)
  • Ketorolac (Toradol) (see Ketorolac)
  • Nabumetone (Relafen, Relifex, Gambaran) (see Nabumetone)
  • Sulindac (Clinoril) (see Sulindac)
  • Tolmetin

Anthranilic Acid Derivatives (Fenamates, Derived from Fenamic Acid)

  • Flufenamic acid
  • Meclofenamic Acid
  • Mefenamic Acid (Ponstel, Ponstan) (see Mefenamic Acid)
  • Tolfenamic Acid

Enolic Acid (Oxicam) Derivatives

  • Droxicam
  • Isoxicam
  • Lornoxicam
  • Meloxicam (Mobic) (see Meloxicam)
  • Oxyphenbutazone (see Oxyphenbutazone): metabolite of phenylbutazone
  • Phenylbutazone (Butazolidine) (see Phenylbutazone): no longer used in humans in the US, but still used in the UK as a last-line agent for ankylosing spondylitis
  • Piroxicam (Feldene) (see Piroxicam)
  • Tenoxicam

Propionic Acid Derivatives

  • Dexibuprofen
  • Dexketoprofen
  • Fenbufen (Cepal, Cinopal, Cybufen, Lederfen, Reugast)
  • Fenoprofen (Nalfon) (see Fenoprofen)
  • Flurbiprofen
  • Ibuprofen (Advil, Brufen, Motrin, Nurofen) (see Ibuprofen)
  • Ketoprofen (Orudis, Oruvail) (see Ketoprofen)
  • Loxoprofen
  • Naproxen (Naprosyn, Aleve) (see Naproxen)
  • Ozaprozin
  • Pranoprofen
  • Tiaprofenic Acid (Surgam, Surgamyl, Tiaprofen)

Salicylates (see Salicylates)

Selective Cyclooxygenase-2 (COX-2) Inhibitors

  • General Comments: the principal advantage of a selective COX-2 inhibitor is to have the anti-inflammatory/anaglesic effects of an NSAID with a decreased risk of gastroduodenal mucosal injury
    • While selective COX-2 inhibitors may protect against colorectal cancer, this benefit has not been definitively proven
  • Celecoxib (Celebrex) (see Celecoxib)
  • Etoricoxib
  • Firocoxib
  • Lumiracoxib: approved for use in the UK
  • Parecoxib
  • Rofecoxib (Vioxx, Ceoxx, Ceeoxx) (see Rofecoxib): withdrawn from worldwide market
  • Valdecoxib (Bextra): withdrawn from worldwide market


  • Nimesulide


  • Clonixin
  • Licofelone
  • H-Harpagide (Figwort, Devil’s Claw)
  • Tenidap


Genetics of Cyclooxgenases (COX-1, COX-2, and COX-3)

Tissue Expression of Cyclooxgenases (COX-1, COX-2, and COX-3)

Physiologic Functions of Cyclooxgenases (COX-1, COX-2, and COX-3)

NSAID’s Function as COX-1/COX-2 Inhibitors

NSAID Inhibition of COX-1

NSAID Inhibition of COX-2



Clinical Effects


Discontinuation of NSAID’s Prior to Surgery/Procedure

Use of NSAID’s in Patients with Concurrent Platelet Dysfunction/Thrombocytopenia

Protective Effects of Non-Aspirin NSAID’s

Drug Interactions

Adverse Effects

Allergic/Immunologic Adverse Effects

Pseudoallergic Reactions

Allergic Reactions

Cardiovascular Adverse Effects

Increased Risk of Atrial Fibrillation (see Atrial Fibrillation)

Increased Risk of Cardiovascular Death/Myocardial Infarction (see Coronary Artery Disease)

Dermatologic Adverse Effects

Morbilliform Rash


Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (TEN) (see Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis)

Endocrinologic Adverse Effects

Drug-Induced Hyporeninemic Hypoaldosteronism (see Hypoaldosteronism)

Gastrointestinal/Hepatic Adverse Effects

General Comments

Colonic Ischemia (Ischemic Colitis) (see Colonic Ischemia)

Dyspepsia (see Dyspepsia)

Elevated Liver Function Tests (LFT’s)/Transaminitis with Acute Hepatocellular Injury (see Drug-Induced Hepatotoxicity)

Peptic Ulcer Disease (PUD)/Gastrointestinal Hemorrhage (see Peptic Ulcer Disease and Gastrointestinal Hemorrhage)

Hematologic Adverse Effects

Aplastic Anemia (see Aplastic Anemia)

Neutropenia (see Neutropenia)

Hemorrhage (Due to Anti-Platelet Effects)

Increased International Normalized Ratio (INR) in Patients on Coumadin Derivatives

Neurologic Adverse Effects

Aseptic Meningitis (see Meningitis)

Cognitive Dysfunction

Increased Risk of Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident)

Psychosis (see Psychosis)

Tinnitus (see Tinnitus)

Ophthalmologic Adverse Effects

Corneal Deposition of Drug Crystals/Corneal Edema

Optic Nerve Pathology

Pulmonary Adverse Effects

Aspirin-Exacerbated Respiratory Disease (AERD) (Aspirin-Intolerant Asthma, AIA) (see Aspirin-Exacerbated Respiratory Disease)

Drug-Induced Pulmonary Eosinophilia (see Drug-Induced Pulmonary Eosinophilia)

Renal Adverse Effects

General Comments

Acute Interstitial Nephritis (see Acute Interstitial Nephritis)

Acute Kidney Injury (AKI) (see Acute Kidney Injury)

Chronic Kidney Disease (CKD) (see Chronic Kidney Disease)

Hyperkalemia (see Hyperkalemia)

Hyponatremia Due to SIADH (see Syndrome of Inappropriate Antidiuretic Hormone Secretion)

Increased Renal Sodium Reabsorption

Increased Risk of Renal Cell Carcinoma

Progression of Existing Chronic Kidney Disease (see Chronic Kidney Disease)

Type 4 Renal Tubular Acidosis (RTA) (see Type 4 Renal Tubular Acidosis)

Vascular Adverse Effects

Increased Risk of Venous Thromboembolism (see Deep Venous Thrombosis and Acute Pulmonary Embolism)

Salicylate Intoxication

NSAID Intoxication