prostaglandin

Prostaglandins (PGs) are eicosanoids synthesized from membrane phospholipids: phospholipase A2 releases arachidonic acid, which is converted by cyclooxygenase (COX-1 and COX-2) into PGG2/PGH2, then further processed into various prostaglandins (PGE2, PGF2α, PGI2/prostacyclin) and thromboxane A2 by specific synthases. COX-1 is constitutively expressed and mediates housekeeping functions (gastric mucosal protection via PGE2, renal blood flow autoregulation, platelet thromboxane production), while COX-2 is inducible during inflammation and produces prostaglandins involved in pain, fever, and inflammation.

Key physiological/pathological roles: - PGE2: vasodilation, hyperalgesia, fever (acts on hypothalamus), uterine contraction, maintains ductus arteriosus patency (used clinically to keep PDA open in certain congenital heart defects; NSAIDs like indomethacin close PDA by inhibiting PGE2), bronchodilation, inhibits gastric acid secretion and increases mucus production (cytoprotective). - PGF2α: uterine and bronchial smooth muscle contraction; used clinically to induce labor/abortion. - PGI2 (prostacyclin): vasodilation, inhibits platelet aggregation (opposes thromboxane A2). - Thromboxane A2 (TXA2): vasoconstriction, promotes platelet aggregation (produced mainly by platelets via COX-1).

Clinical relevance: NSAIDs (nonselective COX inhibitors) reduce prostaglandin synthesis, providing analgesic, antipyretic, and anti-inflammatory effects but also causing GI ulcers (loss of protective PGE2) and renal dysfunction (loss of vasodilatory PGE2/PGI2 in kidney). Aspirin irreversibly inhibits COX-1, reducing thromboxane A2 more than prostacyclin at low doses, providing antiplatelet effects. COX-2 selective inhibitors (e.g., celecoxib) reduce inflammation with less GI toxicity but increase cardiovascular risk due to relative deficiency of prostacyclin. Misoprostol, a PGE1 analog, is used to prevent NSAID-induced ulcers and to induce labor/cervical ripening or as an abortifacient (often combined with mifepristone). Latanoprost (PGF2α analog) is used in glaucoma to increase aqueous outflow. Understanding the prostaglandin pathway is essential for explaining the mechanism and side effects of NSAIDs, aspirin, and various prostaglandin analogs on Step 1/2 exams.