eicosanoids.ppt
- 1. Eicosanoids
- 2. • Def:20 C compounds derived from Arachidonic acid
- 3. classification Eicosanoids Prostanoids Leukotrienes Lipoxins (Lipoxygenase pathway) Prostglandins Thromboxanes (cyclooxygenase pathway)
- 4. • Chemistry : - Prostaglandins – first isolated from prostate tissue & hence the name - present in all tissues - a five C ring
- 5. Naming 1. Capital letter suffix (eg. PGE) denotes substituent group attached to ring 2. PGI is called prostacyclin since it contains additional ring formed by cyclization of side chain
- 6. 3. Number denoted by a subscript after suffix indicates no. of double bonds on side chain (PGE2) 4. PGG & PGH are intermediates during synthesis
- 8. Membrane PL Phospholipase A2 Arachidonic acid • Cycloxygenase Lipoxygenase • Prostaglandins & Leukotrienes & • Thromboxanes Lipoxins
- 9. Membrane PL Phospholipase A2 Arachidonic acid • Cycloxygenase (COX) PGG2
- 10. PGG2 Isomerase Synthase PGD2 PGH2 TXA2 Isomerase Synthase Reductase PGE2 PGI2 PGF2
- 11. Cyclo-oxygenase (COX) + - catecholamines non-steroid anti-inflamm -atory drugs (NSAIDS) Indomethacin,ibuprofen – irreversible inhibitors Paracetamol - reversible
- 12. • Action of Aspirin - Anti-inflammatory - Mechanism : suicide inhibition - acetylates serine residue in the active site of COX - PG synthesis inhibited - Inflammation subsides
- 13. • Platelets can’t regenerate COX -> TxA2 not formed -> platelet aggregation ↓ . So used in prevention of heart attacks • PGI2 also reduced by aspirin, but endothelial cells will resynthesize COX in a few hrs • So aspirin totally blocks TXA2 & partially blocks PGI2 •
- 14. Biochemical action • Mechanism – act as local hormones • Function through G-protein – Adenylate cyclase - cAMP
- 15. Prostaglandins CVS Metabolic Respiratory tract Immunity & inflmmation Ovary & uterus Kidney GIT
- 16. 1. Effect on CVS • PGE2 – vasodilation, ↓ BP • PGF2 – vasoconstriction, ↑BP
- 17. • PGI2 – - Vasodilatation - Inhibits platelet aggregation So protective effect on vessel wall
- 18. • TXA2 - Vasoconstriction - platelet aggregation - promote thrombus formation PGI2 & TXA2 are opposing in activity
- 19. 2. Effect on respiratory tract • PGF – Broncho constrictor • PGE – Bronchodilator • Use: PGE used in aerosols for relieving bronchospasm
- 20. 3. Effect on ovary & uterus • PGF2 stimulates uterine muscles. uses - For medical termination of pregnancy - Inducing labour - Arresting postpartum hemorrhage
- 21. 4. Effect on GIT • PGs - ↓ HCl secretion - ↑ mucin secretion • Use: treatment of peptic ulcer disease
- 22. 5. Effect on kidney • PGs - ↑ Na,K, Cl reabsorption → salt and water retention - renal vasodilation. • Prolonged intake of NSAIDS can cause renal failure.
- 23. 6. Effect on immunity & inflammation • PGD2 & PGE2 - promote inflammation - cause vasodilation leading to edema
- 24. 7. Metabolic effects PGE2 – ↓lipolysis - ↑ glycogenesis - ↑ calcium mobilization from bone &
- 25. Leukotrienes (LTs) • Action: 1.↑ vascular permeability 2.↑ vascular constriction 3.↑ broncho constrictions leading to asthma 4.Cause attraction, activation & migration of leukocytes to the site of injury
- 26. • Slow reacting substance of anaphylaxis (SRS –A) contain LTs • Lipoxins (Lx) • Anti inflammatory & decrease immune response