Stiloz mode of action
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Stiloz etoricoxib mode of action mechanism
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Here is a complete breakdown of Stiloz (etoricoxib) and its mode of action:
Stiloz (Etoricoxib) - Mode of Action
Stiloz is the brand name for etoricoxib, a selective COX-2 inhibitor belonging to the "coxib" class of NSAIDs.
Core Mechanism: Selective COX-2 Inhibition
The cyclooxygenase (COX) enzyme exists in two main isoforms:
| Feature | COX-1 | COX-2 |
|---|---|---|
| Expression | Constitutive (always present) | Inducible (upregulated by cytokines, inflammation, shear stress) |
| Main role | Housekeeping - gastric mucosal protection, platelet TxA2 synthesis, renal regulation | Mediates inflammation, pain, fever; also roles in BP regulation |
| Effect of etoricoxib | NOT inhibited at therapeutic doses | Selectively inhibited |
Etoricoxib has approximately 106-fold selectivity for COX-2 over COX-1 - the second highest selectivity among the coxibs, exceeded only by lumiracoxib. - Goodman & Gilman's Pharmacological Basis of Therapeutics
Step-by-Step Mechanism
-
Arachidonic acid (AA) cascade: When cells are injured or stimulated by cytokines, membrane phospholipids are cleaved by phospholipase A2, releasing arachidonic acid (AA).
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COX-2 induction: Inflammatory stimuli induce COX-2 expression at sites of inflammation. COX-2 converts AA into unstable intermediates PGG2 and PGH2.
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Prostaglandin (PG) synthesis: PGH2 is further converted to pro-inflammatory prostaglandins (PGE2, PGI2, etc.), which cause:
- Vasodilation
- Increased vascular permeability
- Sensitization of nociceptors (pain)
- Fever (via action on the hypothalamus)
-
Etoricoxib's action: Etoricoxib has bulky side chains that fit into the hydrophobic side-pocket of COX-2 (the larger isoform) but are too large to block COX-1 with comparable affinity. This blocks AA conversion at COX-2, reducing prostaglandin synthesis at inflammatory sites.
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Result: Reduced PGE2 and PGI2 at inflamed tissues → analgesia, anti-inflammation, antipyresis.
Why COX-2 Selectivity Matters
- GI advantage: Because COX-1 (the dominant cytoprotective isoform in gastric epithelium) is spared, there is less risk of gastric ulceration compared to non-selective NSAIDs.
- No platelet effect: COX-1-dependent thromboxane A2 (TxA2) in platelets is not inhibited - so platelet function is unaffected (unlike aspirin).
Pharmacokinetics Summary
| Parameter | Value |
|---|---|
| Bioavailability | ~80% (incompletely absorbed) |
| Protein binding | ~92% |
| Half-life (t½) | 20-26 hours (once-daily dosing) |
| Metabolism | Extensive hepatic metabolism (CYP); accumulates in hepatic impairment |
| Renal clearance | Renal insufficiency does not affect clearance |
Clinical Uses
- Osteoarthritis and rheumatoid arthritis
- Ankylosing spondylitis
- Acute gouty arthritis
- Short-term musculoskeletal pain
- Postoperative pain
- Primary dysmenorrhea
Key Adverse Effects
- Cardiovascular risk: Increased risk of myocardial infarction and stroke (class effect of COX-2 inhibitors - because COX-2-derived prostacyclin PGI2 is also cardioprotective and its inhibition tips the balance toward thrombosis)
- Hypertension and edema (renal prostaglandin inhibition)
- No GI benefit if used with aspirin (aspirin negates the gastroprotective advantage)
Note: Etoricoxib is not approved in the USA but is marketed widely under brand names including Stiloz, Arcoxia, and others.
Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics; EMA Arcoxia SmPC; Wikipedia - Etoricoxib
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