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12 Cards in this Set
- Front
- Back
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What are eicosanoids?
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-a class of lipids that include prostaglandins, thromboxanes, leukotrienes and other hydroperoxy- and hydroxyeicosatetraenoic acids
-derived from 20 carbon fatty acids -source is arachnidonic acid, very potent and have short half lives |
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General properties of eicosanoids
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-derived from arachondonic acid
-formed in almost every tissue -activity will differ in different tissues -basal levels are very low -MOAR |
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Biosynthesis of eicosanoids: release of arachidonic acid
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-esterified at sn-2 position, then make free arachidonic acid
-increased intracellular Ca leads to activaiton of and translocation of cytosolic phospholipase A2 to the plasma membrane, this MUST HAPPEN -PLA2 can be inhibited can by glucocorticoids, as they induce lipocortin |
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Prostaglandin and thromboxane synthesis
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Via the action of cyclooxygenase enzyme (COX), which is inhibited by the NSAIDs
--COX1 is constitutively expressed important in decreasing acid secretion in stomach --COX2 induced by inflammation, major role in prostanoid formation in inflammation and cancer |
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Leukotriene synthesis
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-leukotrienes are derived from actions of the lipoxygenase
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Eicosanoid receptors
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-all of them are G-protein linked, major mechanisms are with cAMP and Ca
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Physiological and pathological roles of eicosanoids
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--platelets: TXA2 appears to be a major contributor to increased platelet aggregation, low doses of aspirin target TXA production as a prophylactic tx for heart attacks and stroke. In contrast PGI2 inhibits platelet aggregation and disagregates preformed clumps
--vascular tone: PGI2 relaxes blood vessels locally --Lungs: leukotrienes produce bronchoconstriction and leukocyte invasion (LT inhibitors are good for asthma) --inflammatory responses: PGs and LTs are potent mediators of the immune response and acute inflammatory rxns --kidney: long term use of COX inhibitors is limited by their effects on the kidneys, COX2i are off the market due to their HTN, MI, stroke --uterus: PGFs contract and PGEs relax uterine muscles. In pregnant uterus, both PGs cause uterine m. contraction (abortion agent) --Stomach: PGs inhibit gastric acid secretion and play a major role in maintaining and protective mucosa --Nervous system: PGE2 and PGI2 and LTB4 decrease nociceptor sensitivity and lower |
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more
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s pain, also body temp regulation, fevers mediated by PGE3
--eye: PGF2 decreases intraocular pressure |
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Eicosanoids agonsits
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--PGE agonist:
1. stomach protection, Misoprostol is a PGE1 analog, used to prevent NSAID induced ulcers (30% have diarrhea tho) 2. therapeutic abortion, Dinoprostone, synthetic PGE2 3. impotence ---PGF agonist: 1. glaucoma tx, latanoprost, PGF2 analog |
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NSAIDs
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NSAIDs are COX inhibitors (both 1 and 2), aspirin, drugs inhibit both PG and TX synthesis but not LT synthesis (in fact LT levels may go up)
--low doses are good for anticoagulation properties (TX in the platelets go down, but PGs also go down, which helps clot, so why does this work? It is because aspirin is an irreversible inhibitor COX, so TX in the platelets are never replenished whereas PGs elsewhere are formed) |
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tNSAIDS (non aspirin)
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-Indomethacin one of the first discovered
-Ibuprofen (advil) -naproxen (alleve) -acetominophen (tylenol) posses anti-pyretic and analgesic properties but not anti inflammatory properties --COX2 selective NSAIDs (coxibs) celecoxib |
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Leukotriene inhibitors
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-useful in treating asthma and bronchoconstriciton in response to allergens, 5-lipoxygenase inhibtors and LT receptor inhibitors (LTRAs)
-eicosanoid recptor antags |
