====== 🧪 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.