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Selective and Non Selective NSAIDs. Which one is more potent and safer ?

The Comparative Effect of Selective and Non Selective NSAIDs.

Non Steroidal Anti-inflammatory Drugs, (NSAIDs), are a class of drugs used to relieve inflammation. 

There are 2 major classes of anti-inflammatory drugs, namely steroids and non steroids (NSAIDs).

NSAIDs are devided into 2 classes, they are selective and non-selective NSAIDs. 

The difference between selective and non-selective NSAIDs is based on their work.

Selective classes inhibit only COX-2 enzyme (COX-2 inhibitor) while non-selective NSAIDs inhibit both COX-1 and COX-2.

Examples of non-selective NSAIDs are Sodium diclofenac / Potassium diclofenac, indomethacin, piroxicam, meloxicam, ibuprofen, mefenamic acid.

While the examples of selective  NSAIDs are celecoxib, rofecoxib, valdecoxib.

Both classes have the same pharmacological effects and all of them are indicated to relieve mild pain and inflammation.

Selective NSAIDs were developed to overcome the side effect of Non selective NSAIDs, such as gastric irritation.

The incidence of gastric irritation which is caused by non-selective NSAIDs is quite high.

So, If we view from the safety side to the stomach only,  the selective COX-2 inhibitors become an option.

My question is, Are selective COX-2 inhibitors certainly more potent and safer than non selective NSAIDs ?

Selective NSAIDs (COX-2 Inhibitor)

Selective NSAIDs inhibit COX-2 enzyme only without inhibiting COX-1, so that prostaglandins are not formed.

In clinical use, selective and non-selective NSAIDs are often used to relieve pain in joint inflammation (osteoarthritis / rheumatoid arthritis), local inflammation, chronic skeletal muscle pain.

Non-selective NSAIDs

Non selective NSAIDs have the anti-inflammation effect by inhibiting both COX-1 and COX-2 enzymes.

These enzymes role in catalyzing the prostaglandin (PGE2) and thromboxane which are from arachidonic acid. 

PGE2 is a major mediator of inflammation.

The side effect of non selective NSAIDs to cause gastrointestinal disturbance is due to the inhibition of COX-1 enzyme.

NSAIDs are metabolized mostly in the liver.

Each drug of NSAIDs class has varying half-life (t½) and bioavailability.

Therefore each drug has a different dosing regimen.

Comparison of Non selective and selective NSAIDs Side Effect.

A common side effect of using non selective NSAIDs is gastric irritation. This is due to the inhibition of COX-1.

The main function of prostaglandins which are synthesized from arachidonic acid by using COX-1 enzyme is to protect the gastric mucosa.

When COX-1 is inhibited by non selective NSAIDs, prostaglandins are not formed. It causes Irritation or peptic ulcer.

To minimize the side effect, NSAIDs should be taken after meals (1 hour after meals).

It may be given gastroprotective agents such as proton pump inhibitors (PPIs), sucralfates, or H₂ receptor antagonists.

The incidence of gastric irritation is very low in the use of the selective NSAIDs.

But it  does not mean this class is safe.

Side effects of selective NSAIDs are increasing the risk of myocardial infarction, atherosclerosis, ischemic stroke, and hypertension.

Selective NSAIDs cause imbalance of prostacycline (vasodilator and anti-thrombosis) and thromboxane (vasoconstrictor and thrombosis) levels.

COX-1 is constitutively biosynthesized in the body.

It is essential for thromboxane formation in blood platelets, and for maintaining integrity of the gastrointestinal epithelium.

Thromboxane leads to vasoconstriction and platelet aggregation.

The Comparative Effect of Selective and Non Selective NSAIDs.

COX-2 is formed when there is inflammation.

COX-2 mediates the formation of prostaglandins as an inflammatory response which have vasodilatation and anti-thrombosis effect.

Non-selective NSAIDs inhibit both COX-1 and COX-2 so that the level of  thromboxane and prostacycline are balance.

The Comparative Effect of Selective and Non Selective NSAIDs.

However, selective NSAIDs (COX-2 inhibitors) cause inbalance of thromboxane and prostacycline level.

Increased thromboxane levels cause vasoconstriction and thrombosis (platelet aggregation) that can trigger atherosclerosis, myocardial infarction, ischemic stroke, and hypertension.

These are the adverse effects of COX-2 inhibitors.

The Comparative Effect of Selective and Non Selective NSAIDs.

Based on the consideration of side effects from both classes above, non selective NSAIDs are more recommended for anti-inflammation than selective COX-2 inhibitors.

The combination of both classes is ineffective and unsafe for the patient.

Selectivity of  NSAIDs

The Comparative Effect of Selective and Non Selective NSAIDs.

Adapted from: Feldman M, McMahon AT. Do cyclooxygenase-2 inhibitors provide benefits similar to those of traditional nonsteroidal antiinflammatory drugs, with less gastrointestinal toxicity? Annals of Internal Medicine 2000;132:134-43 (

Byron Cryer and  Mark Feldman (1998) in Cyclooxygenase-1 and Cyclooxygenase-2 Selectivity of Widely Used Nonsteroidal Anti-Inflammatory Drugs express that

  • Flurbiprofen and ketoprofen were COX-1 selective.
  • Ibuprofen and naproxen were essentially nonselective, while others (eg, diclofenac, mefenamic acid) were COX-2 selective.
  • Inhibitory effects of NSAIDs on gastric prostaglandin E2 synthesis correlated with COX-1 inhibitory potency in blood (P <0.001) and with COX-1 selectivity (P <0.01), but not with COX-2 inhibitory potency.


  • The use of NSAIDs is contraindicated for patients with liver and kidney dysfunction
  • NSAIDs can induce asthma attacks. The inhibition of prostaglandin E2 (PGE2) leads to an increased production of leukotrien by the enzyme lipoxygenase. This condition causes high leukotriene levels which its effect is bronchoconstriction.

The Comparative Effect of Selective and Non Selective NSAIDs.