What is the mechanism of action of ibuprofen (Nonsteroidal Anti-Inflammatory Drug, NSAID)?

From the Guidelines

Ibuprofen works by inhibiting cyclooxygenase (COX) enzymes, specifically both COX-1 and COX-2, to reduce the production of prostaglandins that mediate pain, inflammation, and fever. This mechanism of action is crucial for its effectiveness as an analgesic, anti-inflammatory, and antipyretic medication 1. The inhibition of COX enzymes by ibuprofen affects the production of prostaglandins, which are essential for protecting the gastric mucosa and maintaining kidney function, thus explaining the potential side effects such as stomach irritation and reduced kidney perfusion associated with its use 1.

Mechanism of Action Details

• Ibuprofen's inhibition of COX-1 and COX-2 enzymes leads to a decrease in prostaglandin synthesis.
• Prostaglandins play a significant role in mediating inflammation, pain, and fever, as well as in protecting the gastric mucosa and maintaining renal perfusion 1.
• The COX-1 pathway is constitutively expressed in most tissues and is involved in the production of prostaglandins that facilitate gastroduodenal cytoprotection, renal perfusion, and platelet activity 1.
• The COX-2 pathway is inducible by inflammatory stimuli and is primarily responsible for the production of prostaglandins involved in inflammation, pain, and fever 1.

Clinical Implications

• The use of ibuprofen should be tailored to the individual's needs, with the lowest effective dose used for the shortest duration necessary to control symptoms, to minimize the risk of gastrointestinal and renal side effects 1.
• For patients requiring NSAIDs for inflammatory conditions, the choice of NSAID should consider factors such as the duration of treatment, the specific condition being treated, and the patient's risk factors for gastrointestinal and cardiovascular complications 1.
• Selective COX-2 inhibitors may offer an alternative with potentially reduced gastrointestinal risk but at a greater expense, and their use should be considered based on individual patient risk factors and the specific clinical scenario 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Ibuprofen tablets contain ibuprofen which possesses analgesic and antipyretic activities. Its mode of action, like that of other NSAIDs, is not completely understood, but may be related to prostaglandin synthetase inhibition The probable mechanism of action is to inhibit prostaglandin synthesis rather than simply to provide analgesia

The mechanism of action of ibuprofen is not completely understood, but it may be related to prostaglandin synthetase inhibition and inhibition of prostaglandin synthesis. This suggests that ibuprofen works by reducing the production of prostaglandins, which are chemicals in the body that can cause pain and inflammation. 2

• Key points:
  • Ibuprofen has analgesic and antipyretic activities
  • Its mechanism of action is not completely understood
  • It may be related to prostaglandin synthetase inhibition
  • It inhibits prostaglandin synthesis

From the Research

Mechanism of Action of Ibuprofen

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that acts as a potential inhibitor for cyclooxygenase enzymes (COX-1 and COX-2) 3. The mechanism of action of ibuprofen involves the inhibition of prostaglandin synthesis, which plays a key role in pain and inflammation.

Inhibition of Cyclooxygenase Enzymes

Ibuprofen inhibits both COX-1 and COX-2 enzymes, although the exact mechanism of inhibition is not fully understood 4. COX-1 is involved in the maintenance of normal physiologic functions, while COX-2 is induced primarily in sites of inflammation 4. The inhibition of COX-2 is thought to be responsible for the anti-inflammatory and analgesic effects of ibuprofen, while the inhibition of COX-1 may contribute to the gastrointestinal side effects associated with NSAID use 5, 6.

Key Points

• Ibuprofen is a classical anti-inflammatory therapeutic agent that inhibits COX-1 and COX-2 enzymes 3
• The inhibition of COX-2 is thought to be responsible for the anti-inflammatory and analgesic effects of ibuprofen 7
• The inhibition of COX-1 may contribute to the gastrointestinal side effects associated with NSAID use 5, 6
• Ibuprofen has been shown to have anti-tumorigenic and neuroprotective functions, although further research is needed to fully understand these effects 3

Structure and Binding of Ibuprofen to COX-2

The crystal structure of ibuprofen bound to COX-2 has been determined, revealing that only the S-isomer of ibuprofen is bound to the enzyme 7. Mutational analysis has confirmed the role of specific amino acids in the binding and inhibition of COX-2 by ibuprofen 7.

Side Effects of Ibuprofen

The use of ibuprofen is associated with a number of side effects, including gastrointestinal erosions, renal and hepatic insufficiency, and cardiovascular risks 5, 6. These side effects are thought to be dependent on the inhibition of COX-1 and COX-2 enzymes, although the exact mechanisms are complex and multifaceted 6.