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arachidonic acid. by hero salayee
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- 6. 4/5/2015 General pathology 6 CELL PRODUCT Neutrophils Leukotrienes Macrophage/Monocyte Prostaglandins+Leukotriene Platelets Thromboxane Endothelial Cells Prostacyclin CELL SPECIFICITY OF ARACHIDONIC ACID- DERIVED PRODUCTS
- 8. PROSTAGLANDINS[PG] Nomenclature Classification Subscript due to difference in structure of cyclopentane ring. 4/5/2015 8
- 9. Characteristic features : PG Show the effects near the site of synthesis(auto crine & Paracrine effects) Are not stored in the body Are very potent in action. Even in minute very short life span, are destroyed within seconds or few minutes Production increases or decreases in response to diverse stimuli or drugs Act as local hormones 4/5/2015 9
- 10. PROSTAGLANDINS - FUNCTIONS Effects on GIT Effects on Inflammation Effects on Respiratory tract Effects on uterus Effects on CVS 4/5/2015 10
- 11. PROSTAGLANDINS - FUNCTIONS PGI2 Vasodilatation Inhibits platelet aggregation PGA and PGE class prostaglandins lower blood pressure. Effects on CVS 4/5/2015 11
- 13. PROSTAGLANDINS - FUNCTIONS PGF-Bronchoconstriction PGE-Bronchodilator Effects on Respiratory tract 4/5/2015 13
- 14. PROSTAGLANDINS - FUNCTIONS PGE2 Involved in inflammatory response Effects on Inflammation 4/5/2015 14
- 15. PROSTAGLANDINS - FUNCTIONS PGE2 suppress gastric acid secretion Effects on GIT 4/5/2015 15
- 16. Prostacyclins - Chemistry 1)Prostacyclins(PGI) contain another ring between 6 th and 9th carbon atoms & They are synthesized in heart and vascular endothelial cells.
- 17. Inhibit platelet and leukocyte aggregation Decrease T-cell proliferation lymphocyte migration Induce vasodilatation prevent clot formation prostacycline - Functions 4/5/2015 17
- 18. Subscript number denotes number of double bonds have a six membered Oxane ring. Most common Thromboxanes [TX] 4/5/2015 18
- 19. Increase platelet aggregation Vasoconstriction Mobilize intracellular calcium Smooth muscle contraction Bronchoconstriction Thromboxanes - FUNCTIONS 4/5/2015 19
- 20. Grouped into 5 classes [A to E] LTC4 Leukotrines [LT] 4/5/2015 20
- 21. Increase chemotaxis Facilitate inflammation & allergic reactions Contraction of smooth muscle Bronchoconstriction (asthmatic constriction ) Vasoconstriction Leukotrines - Functions 4/5/2015 21
- 22. 4/5/2015 22 Leukotrienes are a hundred times more potent than histamine which provided a rapid response to an allergen
- 23. Lipoxins Lipoxins are a family of conjugated tetraenes also arising in leukocytes. They are formed by the combined action of more than one lipoxygenase.
- 24. Inhibition of Eicosanoid Synthesis : NSAIDs usually do not inhibit lipoxygenase activity at concentrations that inhibit COX activity. NSAIDs may cause more substrate to be metabolized through the lipoxygenase pathways. This leads to an increased formation of the leukotrienes. A 5-LOX inhibitor and antagonists of the leukotriene receptors are used clinically in asthma. Corticosteroids also block all the known pathways of eicosanoid synthesis. 4/5/2015 24
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- 26. CVS GIT NSAID Bronchial Asthma- Ulcerative Colitis Ophthalmologic Pharmacological applications of Eicosanoids 4/5/2015 26
- 27. 1)Cardiovascular uses- pulmonary arterial hypertension, peripheral vascular disease. for keeping the ductus arteriosus open until surgery in neonates carrying certain cardiac malformations and platelet anti- aggregating agents. 2) Digestive Uses- indicated in the treatment of gastro duodenal ulcer and for the prevention of NSAID- induced ulcers. 4/5/2015 27
- 28. 3) Ulcerative Colitis- Mesalamine(mesalazine) or 5 aminosalicyclic acid has antiinflammatory properties in the colon and is used in the treatment of ulcerative colitis (Crohn's disease) it also inhibits lipoxygenases. 4)Bronchial Asthma- PGE2 agonists and leukotrienes receptor antagonists are used for the treatment of bronchial asthma. 4/5/2015 28
- 29. 5) Ophthalmologic Use- lower intraocular pressure 6) Anti- inflammatory use- Inhibitors of cyclo- oxygenases include NSAID 4/5/2015 29
- 30. . NSAID The useful effects in therapeutics are- anti-inflammatory effect analgesic effect antipyretic effect inhibition of platelet aggregation and decrease of thromboembolic risk (well- known with aspirin at low doses) 4/5/2015 30
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- 32. Aspirin inhibits the COX pathway and consequently diverts arachidonic acid metabolites to the LO pathway. This also leads to a decrease in the levels of PGE2, the anti- inflammatory PG. LTC4 synthase overexpression further increases the number of cysteinyl LTs, tilting the balance toward inflammation and broncho constriction Reason for Aspirin induced Asthma 4/5/2015 32
- 33. Reason for Aspirin induced Asthma 4/5/2015 33
Editor's Notes
- Prostaglandins are all derivatives of the hypothetical C20 fatty acid prostanoic acid in which carbon atoms 8 to 12 form a cyclopentane ring (Fig. 25-66a). Prostaglandins A through I differ in the substituents on the cyclopentane ring (Fig. 25-66b):PGAs are ,-unsaturated ketones,PGEs are-hydroxy ketones, PGFs are 1,3-diols, etc. In PGF, the C9 OH group is on the same side of the ring as R1; it is on the opposite side in PGF.The numerical subscript in the namerefers to the number of double bonds contained on the side chains of the cyclopentane ring (Fig. 25-66c). In humans, the most prevalent prostaglandin precursor is arachidonic acid (5,8,11,14-eicosatetraenoic acid), a C20 polyunsaturated fatty acid that has four nonconjugated double bonds.The double bond at C14 is six carbon atoms from the terminal carbon atom (the carbon atom), making arachidonic acid an โ6 fatty acid. As Sune Bergstrรถm and Bengt Samuelsson demonstrated, arachidonic acid is synthesizedsynthesized from the essential fatty acid linoleic acid (also an โ6 fatty acid). This occurs via its desaturation with a 6- desaturase to yield -linolenic acid (GLA), followed by elongation and a second desaturation, this time with a 5- desaturase (Fig. 25-67; Section 25-4E). Prostaglandins with the subscript 1 (the โseries-1โ prostaglandins) are synthesized from dihomo--linolenic acid (DGLA; 8,11,14- eicosatrienoic acid), whereas โseries-2โ prostaglandins are synthesized from arachidonic acid. -Linolenic acid (ALA), another essential fatty acid since the 15-desaturase required for its synthesis occurs only in plants, is a precursor of 5,8,11,14,17-eicosapentaenoic acid (EPA) and the โseries-3โ prostaglandins. Since arachidonate is the primary prostaglandin precursor in humans, we shall mostly refer to the series-2 prostaglandins in our examples. Note, however, that when dietary linoleic acid and -linolenic acid are equally available, the relative activities of the 5- and 6- desaturases are important in determining the relative amounts of these prostaglandin precursors. Hvon Euler thought that these compounds originated in the prostate gland (hence their name) but they were later shown to be synthesized in the seminal vesicles.