Eicosanoids are short-lived lipid mediators derived from arachidonic acid that regulate:

• Inflammation & pain
• Fever
• Platelet function / thrombosis
• Gastric mucosal protection
• Renal blood flow
• Bronchial tone

They are primarily produced via:

• COX pathway → prostaglandins + thromboxane
• 5-LOX pathway → leukotrienes
• (Less emphasized clinically: lipoxins, CYP epoxygenase products)

Membrane phospholipids → (PLA2) → Arachidonic acid

• → COX-1/COX-2 → Prostaglandins (PGE2, PGI2, etc.) + TXA2
• → 5-LOX → Leukotrienes (LTB4, LTC4/D4/E4)

Key clinical idea:

• COX inhibition ↓ prostaglandins (pain/fever/inflammation) but can also ↓ gastric/renal protection
• COX-2 selectivity lowers GI toxicity but can ↑ thrombotic risk (PGI2/TXA2 imbalance)
• Leukotriene blockade helps asthma/allergic disease (especially aspirin-exacerbated respiratory disease)

• NSAID GI toxicity: loss of COX-1 gastric protection → gastritis/ulcer/bleeding risk
• NSAID renal effects: ↓ afferent dilation → ↓ GFR (risk ↑ in CKD, CHF, cirrhosis, dehydration)
• COX-2 selective: fewer ulcers but more thrombosis risk in susceptible patients
• AERD: COX blockade shunts AA toward leukotrienes → bronchospasm; leukotriene blockers help
• Misoprostol prevents NSAID ulcers but causes diarrhea/cramping and is abortifacient

• Arachidonic Acid Pathway
• COX-1 vs COX-2
• Leukotrienes in Asthma
• PGI2–TXA2 Balance