What are non‑steroidal anti‑inflammatory drugs (NSAIDs)?

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What are NSAIDs?

NSAIDs (non-steroidal anti-inflammatory drugs) are a class of medications that inhibit cyclooxygenase (COX) enzymes to block prostaglandin synthesis, producing anti-inflammatory, analgesic (pain-relieving), and antipyretic (fever-reducing) effects. 1

Core Mechanism of Action

NSAIDs work primarily by inhibiting the COX enzymes that are responsible for producing prostaglandins, which mediate inflammation, pain, and fever. 2 This enzyme inhibition is the fundamental mechanism that explains their therapeutic benefits across multiple conditions. 3

Classification by COX Selectivity

NSAIDs are divided into two main categories based on which COX enzymes they inhibit:

Non-Selective NSAIDs (Traditional NSAIDs)

  • These agents reversibly inhibit both COX-1 and COX-2 enzymes, providing effective pain relief and anti-inflammatory effects. 1, 2
  • Common examples include ibuprofen, naproxen, and indomethacin. 4
  • Aspirin is unique because it irreversibly inhibits both COX enzymes, unlike other traditional NSAIDs. 1, 2

Selective COX-2 Inhibitors (Coxibs)

  • These medications have higher affinity for COX-2 than COX-1, which was intended to reduce gastrointestinal side effects. 1, 2
  • Celecoxib is the primary example currently available in the United States. 4, 5
  • All selective COX-2 inhibitors increase the risk of thrombotic cardiovascular events, myocardial infarction, and stroke. 4

Chemical Classification

The American Heart Association recognizes that NSAIDs can be organized into 9 main chemical groups, including salicylate derivatives (aspirin, salsalate) and various other chemical classes. 4

Clinical Uses

NSAIDs are among the most widely prescribed medications worldwide and are used to treat:

  • Pain from various sources (acute injuries, postoperative pain, chronic conditions). 6, 5
  • Inflammation and swelling from medical conditions. 6
  • Different types of arthritis (rheumatoid arthritis, osteoarthritis). 6, 5
  • Menstrual cramps and fever. 6

Critical Safety Warnings

Cardiovascular Risks

  • NSAIDs may increase the chance of heart attack or stroke that can lead to death, with risk increasing with longer use and in people with heart disease. 6
  • NSAIDs should never be used right before or after coronary artery bypass graft (CABG) surgery. 6
  • The cardiovascular risk correlates with COX-2 selectivity—diclofenac shows a hazard ratio of 2.40 for mortality in post-MI patients, while ibuprofen shows 1.50. 4

Gastrointestinal Risks

  • NSAIDs can cause fatal gastrointestinal ulcers, bleeding, and perforation at any time during treatment, which can happen without warning symptoms and may cause death. 6
  • Risk increases with: older age, history of GI ulcers, concurrent use of corticosteroids or anticoagulants, longer duration of use, smoking, and alcohol consumption. 6
  • Traditional non-selective NSAIDs carry significant risk of gastritis and GI bleeding due to COX-1 inhibition. 4

Other Important Risks

  • NSAIDs can cause renal dysfunction, particularly in patients with pre-existing kidney insufficiency. 4
  • Older adults have substantially higher risk of adverse effects—NSAIDs were involved in 23.5% of hospitalizations for adverse drug reactions in this population. 2

Recommended Approach to NSAID Selection

For chronic musculoskeletal pain, start with acetaminophen, low-dose narcotics, or non-acetylated salicylates as first-line therapy. 4 If initial therapy proves insufficient, advance to non-selective NSAIDs like naproxen. 4 Only use NSAIDs with increased COX-2 selectivity if discomfort persists despite other options, and always use the lowest effective dose for the shortest possible duration. 4

Key Clinical Pitfalls to Avoid

  • Never assume NSAIDs are benign because many are available over-the-counter—they carry serious cardiovascular and gastrointestinal risks that require careful patient selection. 6
  • Patients should not use over-the-counter NSAIDs for more than 10 days without consulting a healthcare provider. 6
  • NSAIDs should not be used by pregnant women late in pregnancy. 6
  • Aspirin, while technically an NSAID, does not increase heart attack risk like other NSAIDs, but can cause bleeding in the brain, stomach, and intestines. 6

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Pharmacokinetics and Pharmacodynamics

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

3
Research

Clinical pharmacology of non-steroidal anti-inflammatory drugs: a review.

Anti-inflammatory & anti-allergy agents in medicinal chemistry, 2012

4
Guideline

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Classification and Usage

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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