Non-steroidal anti-inflammatory drugs (NSAIDs)

Non-steroidal anti-inflammatory drugs (NSAIDs)
Last update: 19-12-2023

How else can it be called?

  • Non-steroidal anti-inflammatory drugs

  • NSAIDs

  • Non-corticosteroid anti-inflammatory drugs

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

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of medications that act by inhibiting the production of prostaglandins. Their primary effects include reducing inflammation (anti-inflammatory), alleviating pain (analgesic), and lowering fever (antipyretic).

They are distinguished from steroidal anti-inflammatories, such as corticosteroids, by their name, but more significantly, by their distinct mechanisms of action, applications, and uses.

Acetylsalicylic acid, known as Aspirin®, was the first NSAID used and all the others NSAIDs derive from the study of its chemical composition.

There are many NSAIDs today in the market available over-the-counter (sans prescription). However, it is important to seek the guidance of a doctor for optimal usage, particularly due to their potential risks, including digestive bleeding and heart problems.

What is the mechanism of action of non-steroidal anti-inflammatory (NSAIDs)?

NSAIDs work by inhibiting a specific type of enzyme known as cyclooxygenases or COX, which exist in two primary forms: COX-1 and COX-2.

COX-1 plays a significant role in platelet aggregation, an essential process in blood clotting, and in the protection of the stomach lining.

COX-2 is a key mediator of inflammatory regulation and modulate pain and body temperature changes.

These enzymes are proteins that are activated when the body receives an attack (for example, an infection or trauma) and act as a defense mechanism. However, their overactivity can lead to unwanted issues.

COX enzymes play a protective role for various organs, particularly the kidneys, stomach, intestines, and cardiovascular system.

Hence, while NSAIDs are effectively to relieve some symptoms, they also carry potential risks of adverse effects on the kidneys and heart, as well as the possibility of inducing digestive bleeding.

What are anti-inflammatory drugs (NSAIDs) commonly used for?

These medications provide symptomatic relief from pain and inflammation in chronic conditions, such as osteoarthritis and rheumatoid arthritis. They also prove beneficial in injuries, fractures, and sprains from sports activities and various soft tissue traumas, by reducing pain and inflammation.

Furthermore, they prove effective in managing post-surgical pain, alleviating discomfort post-dental procedures, easing menstrual cramps (dysmenorrhea), as well as in the case of headaches and migraines.

No specific NSAID has demonstrated superior efficacy over others. The choice of medication primarily hinges on the risk factors and potential adverse effects, which may slightly vary among different NSAIDs.

All of them are recommended for conditions involving inflammation such as rheumatism (inflammatory and degenerative):

Sometimes they are recommended for conditions without inflammation and pain such as:

  • Bursitis
  • Tendinopathy
  • Tenosynovitis
  • Sprains
  • Capsulitis

What are the most common non-steroidal anti-inflammatories (NSAIDs)?

NSAIDs can be grouped on:

  1. Salicylates: Like aspirin® and diflunisal.
  2. Paracetamol (acetaminophen or para-hydroxyacetanilide).
  3. Acetic acid derivatives: diclofenac, indomethacin, sulindac, etodolac, tolmetin, ketorolac, nabumetone.
  4. Fenamates: mefenamic acid, meclofenamate and flufenamic acid.
  5. Propionic acid derivatives: ibuprofen, naproxen.
  6. Phenolic acids or oxicams: piroxicam, meloxicam.
  7. Selective COX-2 or COXIB inhibitors: celecoxib.

There is another group that is not included as NSAIDs by expert reviews, although they work in a similar way: pyrazolones such as metamizole or dipyrone and phenylbutazone.

Pyrazolones have very potent anti-inflammatory capabilities, but as they have serious side effects on the blood, especially blood dyscrasias, they have been subject to restrictions.

What are the main characteristics of each group of non-steroidal anti-inflammatory drugs (NSAIDs)?


It is recommended to avoid salicylates in children with fever due to the risk of developing Reye's syndrome (a severe abnormal reaction that affects the liver and brain).

Acetylsalicylic acid (ASA) remains the preferred drug under cost-effectiveness criteria for its anti-inflammatory properties. However, it may have gastrointestinal side effects that have left it only as an alternative choice. Lysine acetylsalicylate (lysine aspirin) may improve gastric tolerance.


Non-opioid analgesics like paracetamol offer improved gastrointestinal tolerance and may be useful when the primary symptom is pain and not inflammation.

However, paracetamol (acetaminophen) overdose can cause severe liver failure.

Acetic acid derivatives:

Indomethacin is associated with a notable incidence of gastrointestinal and central nervous system effects, including headaches and vertigo.

Diclofenac boasts a relatively low incidence of adverse effects and could be a good choice. It is available on oral tablets, injections, eye drops, pediatric doses, topical gel, and even combined formulations with the antiulcer drug misoprostol.


Meclofenamic acid is the most powerful anti-inflammatory of this group, but it may cause diarrhea as a side effect.

Propionic acid derivatives:

Ibuprofen is relatively safe and effective as a treatment of acute pain but it is a weak anti-inflammatory and tends to be used more as a pain reliever.

Phenolic acids or oxicams:

Piroxicam allows a single daily dose, and other drugs such as diclofenac (in delayed-release tablets) or tenoxicam are administered twice a day.

Selective inhibitors of COX-2 or COXIB

COX-2 inhibiting NSAIDs or selective COX-2 inhibitors are medications designed to mitigate side effects like digestive bleeding although they tend to increase the risk of heart problems.

What are the most frequent adverse effects of NSAIDs?

The main adverse effects of NSAIDs are:

  • Digestive: Gastrointestinal bleeding and peptic ulcers.
  • Increased cardiovascular risk: Raise the risk of a heart attack, a stroke or peripheral arterial disease.
  • Increased risk of bleeding, particularly in the stomach and intestines: It occurs particularly with high doses, prolonged treatment time, combination with aspirin® or another NSAIDs or with anticoagulant medications.
  • Risk of kidney damage or exacerbation of kidney diseases.
  • Increased risk of suffering from anemia.

It's important to consider that NSAIDs may lead to stomach pain, a sensation of heaviness, heartburn, nausea, vomiting, dizziness, headaches, fatigue, drowsiness, and increased nocturnal urination.

At times, they might cause ringing in the ears or dizziness, especially with higher doses.

Occasionally, they can trigger skin rashes and hives, while very rarely affecting blood cell count and coagulation.

They should be avoided if there is an allergy to the drug, asthma with intolerance to NSAIDs, peptic ulcers, during pregnancy or breastfeeding, and in pediatric patients (except for paracetamol and diclofenac).

Phenylbutazone use should be avoided in cardiovascular diseases, epilepsy, and in patients treated with insulin or antidiabetics.

Fentiazac is not recommended during pregnancy, particularly in the days before delivery due to the risk of uterine adynamia and premature closure of the ductus arteriosus.

These medications should not be associated with oral anticoagulants, lithium salts, digoxin, antihypertensives and diuretics, as it may either increase or reduce their effects.

Combining aceclofenac or piroxicam with acetylsalicylic acid can diminish the effects of both medications.

What are the general recommendations when usings NSAIDs?

Experts provide specific recommendations when initiating an NSAID treatment:

  1. Use NSAIDs primarily for pain management.
  2. If there is a more effective alternative for pain relief, choose it first; if no improvement is observed, consider NSAIDs.
  3. Start with the lowest effective dose and use them for the shortest duration.
  4. Assess the cardiovascular risk. Naproxen is the one that poses the least risk to the heart.
  5. Avoid them in people with heart failure.
  6. Avoid using NSAIDs with anticoagulant medications at the same time due to an increased risk of bleeding; COXIBs present the lowest risk.
  7. Avoid taking NSAIDs at the same time with aspirin® post-heart attack, because the efficacy of the aspirin® is reduced or lost.
  8. Evaluate the risk of digestive bleeding.
  9. Do not use two or more NSAIDs at the same time. If necessary, for example, in postoperative pain, consider a short-term combination of paracetamol (acetaminophen) with another NSAID.
  10. When using antiulcer medication to counteract NSAID side effects, opt for proton pump inhibitors (e.g., omeprazole, lansoprazole).
  11. Prefer paracetamol (acetaminophen) over other NSAIDs for individuals at a high risk of stomach bleeding.
  12. For patients with rheumatic disease, regularly monitor kidney function by testing glomerular filtration.
  13. Avoid the use of NSAIDs in people with liver cirrhosis, inflammatory bowel disease, advanced chronic kidney disease and kidney failure.

Active ingredients and brand names of non-steroidal anti-inflammatory drugs (nsaids)

  • Salicylates
    • Acetylsalicylic acid
    • Benorylate
    • Diflunisal
    • Lysine acetylsalicylate
    • Salsalate (Ethersalate)
    • Salsalate (Disalicylic acid, Salicylsalicylic acid)
  • Non-opioid analgesics
    • Paracetamol (Acetaminophen)
  • Derivatives of acetic acid or arylacetics
    • Aceclofenac
    • Diclofenac
    • Diclofenac + Misoprostol
    • Fentiazac
    • Nabumetone
  • Fenamates
    • Meclofenamic acid
    • Mefenamic acid
    • Niflumic acid
  • Derivatives of propionic or arylpropionic acid
    • Butibufen
    • Fenbufen
    • Flurbiprofen
    • Ibuprofen
    • Ibuproxam
    • Ketoprofen
    • Naproxen
    • Thiaprofenic acid
  • Indoleacetic derivatives
    • Acemetacin
    • Glucametacin
    • Indomethacin
    • Ketorolac
    • Oxamethacin
    • Proglumetacin
    • Sulindac
    • Tolmetin
  • Phenolic acids or oxicams
    • Droxicam
    • Piroxicam
    • Tenoxicam
  • Selective COX-2 inhibitors or Anti-COX2 anti-inflammatories or COXIB
    • Celecoxib
    • Etoricoxib
    • Parecoxib
  • Pyrazolones and analogues
    • Dipyrone
    • Feprazone
    • Nifenazone
    • Phenylbutazone (Butadione)
    • Suxibuzone
Medically reviewed by Yolanda Patricia Gómez González Ph.D. on 19-12-2023


  • Review of Rheumatology (2012), Nona T. Colburn, ISBN 978-1-84882-092-0 , Pag. 471.
  • Pathology of the Gastrointestinal Tract, 2017, Fátima Carneiro, Paula Chaves, Arzu Ensari, ISBN 978-3-319-40559-9, Pag. 561.
  • Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e © 2019. Chapter 38. Pharmacotherapy of Inflammation, Fever, Pain, and Gout. McGRAW-HILL ISBN-13: 978-1259584732.

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