🧬 Cyclo-oxygenase (COX) enzymes are key in converting arachidonic acid → prostanoids (prostaglandins, prostacyclins, thromboxanes).
They regulate inflammation, pain, fever, clotting, gastric protection, and renal blood flow.
Different isoforms (COX-1, COX-2, COX-3) explain why NSAIDs and related drugs have both therapeutic effects and side effects.
🔎 Types of COX Enzymes
- COX-1 (Constitutive) 🛡️
- Present in most tissues under normal conditions.
- Maintains gastric mucosa, renal blood flow, and platelet aggregation (via thromboxane A₂).
- COX-2 (Inducible) 🔥
- Upregulated by inflammation (cytokines, growth factors, tumour promoters).
- Produces pro-inflammatory prostaglandins → pain, fever, swelling.
- Also constitutively expressed in some tissues (brain, kidney).
- COX-3 (Variant of COX-1) 🧠
- Found in the CNS; role still unclear.
- May mediate pain and fever centrally.
- Inhibited by paracetamol → explains analgesic/antipyretic effect but weak anti-inflammatory action.
⚙️ Functions of COX Enzymes
- Prostaglandins (PGs): Pain, fever, inflammation; gastric and renal protection.
- Prostacyclin (PGI₂): Vasodilation, inhibits platelet aggregation (protective for CV system).
- Thromboxane (TXA₂): Vasoconstriction, promotes platelet aggregation (pro-thrombotic).
💊 Clinical Significance
- NSAIDs (ibuprofen, aspirin) 🩹
- Block COX-1 + COX-2 → ↓ PGs → relief of pain, fever, inflammation.
- Side effects: gastric irritation, ulcer, bleeding (via COX-1 inhibition).
- COX-2 inhibitors (Coxibs e.g. celecoxib) ⚖️
- Selectively inhibit COX-2 → pain/inflammation relief with fewer GI side effects.
- Risk: ↑ cardiovascular events (MI, stroke) due to reduced prostacyclin without reduced thromboxane.
- Paracetamol 💊
- Weak peripheral COX inhibitor, may act via COX-3 in CNS.
- Good for analgesia + fever but little anti-inflammatory effect.
⚠️ Adverse Effects
- COX-1 inhibition:
- Gastritis, peptic ulcers, GI bleeding.
- Impaired platelet aggregation → ↑ bleeding risk.
- COX-2 inhibition:
- Lower GI risk ✅
- Higher CV risk ❌ (MI, stroke).
- Renal side effects: sodium/water retention, hypertension, renal impairment.
📚 Reference
