Multiple Types of NSAIDs Compared

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Comparison From**

This is an interesting and informative comparison of dozens of NSAIDs, many I’ve never heard of, showing the critical factors in deciding which ones to use under which circumstances.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications worldwide.

Nonsteroidal anti-inflammatory drugs possess anti-inflammatory, analgesic, and antipyretic properties, and inhibit thrombocyte aggregation.

NSAIDs are used primarily to treat inflammation, relieve mild-to-moderate pain, and reduce fever. NSAIDs also are included in many fever reducers, cough, cold and allergy preparations. 

NSAIDs block cyclooxygenase enzymses and reduce prostaglandins throughout the body.

As a result, ongoing inflammation, pain, and fever are reduced.

Since the prostaglandins that protect the gastric mucosa and support the platelets and blood clotting also are reduced, NSAIDs can make stomach lining susceptible to damage, and promote ulcers in the stomach and bleeding.

There are many different types of NSAIDs, which are categorized according to their chemical structures.

  • Salicylates
  • Arylalkanoic acids
  • Pyrroles
  • Arylpropionic acids (profens)
  • Enolic acids (oxicams)
  • Fenamates
  • Pyrazolones:
  • Sulphonanilides
  • Napthylalkanones:
  • COX-2 Inhibitors

I didn’t know there were so many different types/groups of these medications – I’ve listed just the groups here, but the web page shows all the specific NSAIDs fo each group.

The anti-inflammatory activity of NSADs in descending order:

  • indomethacin > diclofenac > piroxicam > ketoprofen > lornoxicam > ibuprofen > ketorolac > acetylsalicylic acid

Differences between NSAIDs

The principal differences among NSAIDs lie in the time to onset and duration of action.

Also, these drugs vary in their potency and how they are eliminated from the body.

Another important difference is their ability to cause ulcers and promote bleeding.

The more an NSAID blocks COX-1, the greater is its tendency to cause ulcers and promote bleeding.

The web page identifies several NSAIDs with unusual properties, but I’ve chosen to list only a few of them here.


Aspirin is a unique NSAID because it is the only NSAID able to inhibit blood clotting for a prolonged period (4 to 7 days). This antiplatelet effect of aspirin makes it an ideal therapy for preventing the blood clots that cause heart attacks and strokes.

Most other NSAIDs inhibit the clotting of blood for only a few hours.


Diclofenac is relatively long acting (6 to 8 hours) but it has a very short half-life. Diclofenac is also a unique NSAID. There is some evidence that diclofenac inhibits lipoxygenase enzymes, and activate the nitric oxide-cGMP antinociceptive pathway.

There is also speculation that diclofenac may inhibit phospholipase A2. These additional actions may explain the high potency of diclofenac – it is one the most potent NSAIDs.

As an analgesic, diclofenac is 6 times more potent than indomethacin and 40 times as potent as aspirin in the phenyl benzoquinone-induced writhing assay in mice.

Diclofenac is associated with the highest risk of heart attack and stroke.


Ketoprofen, unlike many NSAIDs, inhibits the synthesis of leukotrienes and leukocyte migration into inflamed joints in addition to inhibiting the biosynthesis of prostaglandins.

Ketoprofen stabilizes the lysosomal membrane during inflammation, resulting in decreased tissue destruction. Although it is less potent than indomethacin, its gastrotoxicity is about the same. Ketoprofen may cause photosensitivity.


Meloxicam was initially introduced as a selective COX-2 inhibitor. However, it is less selective for COX-2 than is celecoxib. Meloxicam causes fewer GI complications than piroxicam.

Comparative efficacy: which NSAID is the best?

It is a common misconception that all NSAIDs are therapeutically equally effective and any one of them could be used for the given condition.

For example, ankylosing spondylitis responds better to a particular NSAID like indomethacin. It is probably related to its stronger inhibition of prostaglandin synthesis.

In a comparative single-blind trial of 10 anti-inflammatory drugs the greatest pain relief in rheumatoid arthritis was achieved by diclofenac, indomethacin, naproxen and tolfenamic acid.

The least effective drugs were ketoprofen and proquazone. Acetylsalicylic acid, azapropazone, carprofen and ibuprofen were considered intermediate in efficacy.

Side Effects

NSAIDs can cause a number of side effects.

The two main adverse reactions, associated with NSAIDs relate to gastrointestinal tract and renal function.

The adverse effects are usually dose-dependent, and in some cases are severe enough to pose serious health risks.

Cardiovascular side effects

Both COX-2-selective and nonselective NSAIDs may cause adverse cardiovascular effects9, including increased risk of myocardial infarction, stroke, and thrombosis.

Gastrointestinal adverse effects

The main problem with of NSAIDs is that they can cause ulcers in the stomach, esophagus, and small intestine.

Common gastrointestinal side effects include: nausea, vomiting, dyspepsia, peptic ulcers, perforations of the upper gastrointestinal tract, and gastrointestinal bleeding.

Hypertension (High blood pressure)

NSAIDs may potentially increase blood pressure or aggravate existing hypertension. All NSAID users experience some degree of salt and water retention, and hypertension occurs in less than 10% of users.

Kidney damage (nephrotoxicity)

NSAIDs reduce the blood flow to the kidneys, which makes them work more slowly.

This is due to the inhibition of production of the vasodilatory renal prostaglandins. When the kidneys are not working well, fluid builds up in the body leading to edema. The more fluid in the bloodstream — the higher blood pressure. The reduced blood flow can permanently damage the kidneys. It can eventually lead to kidney failure and require dialysis.

Long-term use of oxicams (piroxicam, meloxicam) and ketorolac is associated with an increased risk of chronic kidney disease

Composite cardiovascular /renal risk (in ascending order):

  • rofecoxib > indomethacin > diclofenac > celecoxib > naproxen > ibuprofen > meloxicam

Allergic reactions

NSAIDs can also cause extreme allergy.

People suffering from asthma are more likely to experience serious allergic reaction. Many specialists recommend that people who have asthma stay away from any NSAID, especially if they have sinus problems or nasal polyps. Individuals with a serious allergy to one NSAID are likely to experience a similar reaction to a different NSAID.

NSAIDs do not directly cause bleeding, but they make bleeding worse, for example, when there is a cut.

A meta-analysis of 11 case-control studies and one cohort study found that ibuprofen was significantly less toxic than other NSAID.


All NSAIDs are similarly effective.

The choice of which NSAID to try first is usually empiric. 

If one doesn’t provide adequate pain control, try switching to another.

All NSAIDs when used chronically can contribute to the development of ulcers.

So follow with your doctor closely and watch for signs or symptoms of gastrointestinal bleeding such as stomach pain and blood in the stools.

Further Reading

Head-to-head comparisons of NSAIDs:

**The website on which I found this information,, is certified as “ethical” by displaying the HONCode logo at the bottom of each web page:

This is a good indicator to look for when browsing for health information.


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