🧪 Cyclooxygenase (COX) Inhibition

🧪 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.

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