🧪 Cyclooxygenase (COX) Inhibition
📌 Definition
Cyclooxygenase inhibition refers to the blocking of COX enzymes—key enzymes involved in the conversion of arachidonic acid into prostaglandins and thromboxanes, which mediate pain, inflammation, fever, and platelet aggregation.
This mechanism is the primary action of NSAIDs (Nonsteroidal Anti-Inflammatory Drugs).
🧬 COX Isoenzymes
| Isoform | Location | Function |
|---|---|---|
| COX-1 | Constitutive (expressed in most tissues) | Protects gastric mucosa, supports renal perfusion, enables platelet aggregation (via TXA₂) |
| COX-2 | Inducible (upregulated in inflammation) | Produces prostaglandins involved in pain, fever, inflammation |
| COX-3 *(hypothetical)* | Variant of COX-1 (not well understood) | May be inhibited by paracetamol/acetaminophen |
💊 NSAIDs and COX Inhibition
NSAIDs reduce pain and inflammation by inhibiting one or both COX isoforms:
| Drug Type | COX Selectivity | Examples |
|---|---|---|
| Non-selective NSAIDs | Inhibit COX-1 and COX-2 | Ibuprofen, Ketorolac, Diclofenac |
| COX-2 selective inhibitors | Preferentially inhibit COX-2 | Celecoxib, Etoricoxib |
🧠 Clinical Relevance in Surgery
Inhibition of COX-1 leads to:
- ↓ Thromboxane A₂ → ↓ Platelet aggregation → ↑ Bleeding risk
- ↑ Risk of gastrointestinal ulceration
Inhibition of COX-2 leads to:
- ↓ Inflammation and pain (therapeutic effect)
- Minimal effect on platelets → safer in surgical patients
⚠️ Implications in Neurosurgery
- Concern: NSAIDs (especially COX-1 inhibitors) might increase postoperative bleeding
- Evidence: Recent meta-analyses suggest no significant increase in bleeding with NSAID use after craniotomy when used judiciously (Cardoso et al., *Neurosurgery* 2025)
🧾 Summary
Cyclooxygenase inhibition is central to the action of NSAIDs. While effective for analgesia and anti-inflammation, COX-1 inhibition may impair platelet function, potentially increasing bleeding risk. COX-2 selective inhibitors offer a safer alternative in high-risk surgical contexts.