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Inflammation PowerPoint Presentation

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Slide 1 - Prostaglandin, Leukotriene, and Thromboxane Synthesis Eric Niederhoffer SIU-SOM Pathway overview Prostaglandin receptors Pathway details Differential actions of cyclooxygenases COX-1 and COX-2 comparison COX-1 specificity of common NSAIDs Tissue comparison
Slide 2 - Prostaglandin, Leukotriene, and Thromboxane Synthesis Eric Niederhoffer SIU-SOM Pathway overview Prostaglandin receptors Pathway details Differential actions of cyclooxygenases COX-1 and COX-2 comparison COX-1 specificity of common NSAIDs Tissue comparison Pathway Overview Linoleic acid Thromboxane A2 synthase Lipoxygenase Prostaglandin H2 synthase
Slide 3 - Prostaglandin, Leukotriene, and Thromboxane Synthesis Eric Niederhoffer SIU-SOM Pathway overview Prostaglandin receptors Pathway details Differential actions of cyclooxygenases COX-1 and COX-2 comparison COX-1 specificity of common NSAIDs Tissue comparison Pathway Overview Linoleic acid Thromboxane A2 synthase Lipoxygenase Prostaglandin H2 synthase Prostaglandin Receptors http://www.caymanchem.com/app/template/scientificIllustrations%2CIllustration.vm/illustration/2018/a/z
Slide 4 - Prostaglandin, Leukotriene, and Thromboxane Synthesis Eric Niederhoffer SIU-SOM Pathway overview Prostaglandin receptors Pathway details Differential actions of cyclooxygenases COX-1 and COX-2 comparison COX-1 specificity of common NSAIDs Tissue comparison Pathway Overview Linoleic acid Thromboxane A2 synthase Lipoxygenase Prostaglandin H2 synthase Prostaglandin Receptors http://www.caymanchem.com/app/template/scientificIllustrations%2CIllustration.vm/illustration/2018/a/z Pathway Details Phospholipase A2 (or PLC) Membrane phospholipids Cyclooxygenase O2 Arachidonic acid PGG2 PGH2 PG hydroperoxidase 2GSH GSSG NSAIDS (aspirin) Anti-inflammatory steroids Glucocorticoids (mediated by lipocortin-Ca2+) IL-1R IL-1 (inflammation) PGI2 (PC) PGE2 PGI2 synthase PGE2 synthase PGD2 PGF2a PGD2 synthase PGF2 synthase PGH2 synthase LTD4 LTE4 LTB4 LTC4 Glutathione S-transferase LTA4 TXA2 TXA2 synthase PGJ2
Slide 5 - Prostaglandin, Leukotriene, and Thromboxane Synthesis Eric Niederhoffer SIU-SOM Pathway overview Prostaglandin receptors Pathway details Differential actions of cyclooxygenases COX-1 and COX-2 comparison COX-1 specificity of common NSAIDs Tissue comparison Pathway Overview Linoleic acid Thromboxane A2 synthase Lipoxygenase Prostaglandin H2 synthase Prostaglandin Receptors http://www.caymanchem.com/app/template/scientificIllustrations%2CIllustration.vm/illustration/2018/a/z Pathway Details Phospholipase A2 (or PLC) Membrane phospholipids Cyclooxygenase O2 Arachidonic acid PGG2 PGH2 PG hydroperoxidase 2GSH GSSG NSAIDS (aspirin) Anti-inflammatory steroids Glucocorticoids (mediated by lipocortin-Ca2+) IL-1R IL-1 (inflammation) PGI2 (PC) PGE2 PGI2 synthase PGE2 synthase PGD2 PGF2a PGD2 synthase PGF2 synthase PGH2 synthase LTD4 LTE4 LTB4 LTC4 Glutathione S-transferase LTA4 TXA2 TXA2 synthase PGJ2 Differential Actions of Cyclooxygenases NSAIDs COX1 Constitutive COX2 Inducible Inflammatory Endothelial integrity Vascular patency Gastric mucosal integrity Bronchodilation Renal function Platelet function Inflammation Unwanted side-effects Therapeutic anti-inflammatory effects PGE2 PGF2a Proteases PGI2 PGE2 TXA2 Housekeeping
Slide 6 - Prostaglandin, Leukotriene, and Thromboxane Synthesis Eric Niederhoffer SIU-SOM Pathway overview Prostaglandin receptors Pathway details Differential actions of cyclooxygenases COX-1 and COX-2 comparison COX-1 specificity of common NSAIDs Tissue comparison Pathway Overview Linoleic acid Thromboxane A2 synthase Lipoxygenase Prostaglandin H2 synthase Prostaglandin Receptors http://www.caymanchem.com/app/template/scientificIllustrations%2CIllustration.vm/illustration/2018/a/z Pathway Details Phospholipase A2 (or PLC) Membrane phospholipids Cyclooxygenase O2 Arachidonic acid PGG2 PGH2 PG hydroperoxidase 2GSH GSSG NSAIDS (aspirin) Anti-inflammatory steroids Glucocorticoids (mediated by lipocortin-Ca2+) IL-1R IL-1 (inflammation) PGI2 (PC) PGE2 PGI2 synthase PGE2 synthase PGD2 PGF2a PGD2 synthase PGF2 synthase PGH2 synthase LTD4 LTE4 LTB4 LTC4 Glutathione S-transferase LTA4 TXA2 TXA2 synthase PGJ2 Differential Actions of Cyclooxygenases NSAIDs COX1 Constitutive COX2 Inducible Inflammatory Endothelial integrity Vascular patency Gastric mucosal integrity Bronchodilation Renal function Platelet function Inflammation Unwanted side-effects Therapeutic anti-inflammatory effects PGE2 PGF2a Proteases PGI2 PGE2 TXA2 Housekeeping COX-1 and COX-2 Comparison http://elfstrom.com/arthritis/nsaids/actions.html
Slide 7 - Prostaglandin, Leukotriene, and Thromboxane Synthesis Eric Niederhoffer SIU-SOM Pathway overview Prostaglandin receptors Pathway details Differential actions of cyclooxygenases COX-1 and COX-2 comparison COX-1 specificity of common NSAIDs Tissue comparison Pathway Overview Linoleic acid Thromboxane A2 synthase Lipoxygenase Prostaglandin H2 synthase Prostaglandin Receptors http://www.caymanchem.com/app/template/scientificIllustrations%2CIllustration.vm/illustration/2018/a/z Pathway Details Phospholipase A2 (or PLC) Membrane phospholipids Cyclooxygenase O2 Arachidonic acid PGG2 PGH2 PG hydroperoxidase 2GSH GSSG NSAIDS (aspirin) Anti-inflammatory steroids Glucocorticoids (mediated by lipocortin-Ca2+) IL-1R IL-1 (inflammation) PGI2 (PC) PGE2 PGI2 synthase PGE2 synthase PGD2 PGF2a PGD2 synthase PGF2 synthase PGH2 synthase LTD4 LTE4 LTB4 LTC4 Glutathione S-transferase LTA4 TXA2 TXA2 synthase PGJ2 Differential Actions of Cyclooxygenases NSAIDs COX1 Constitutive COX2 Inducible Inflammatory Endothelial integrity Vascular patency Gastric mucosal integrity Bronchodilation Renal function Platelet function Inflammation Unwanted side-effects Therapeutic anti-inflammatory effects PGE2 PGF2a Proteases PGI2 PGE2 TXA2 Housekeeping COX-1 and COX-2 Comparison http://elfstrom.com/arthritis/nsaids/actions.html COX-1 Specificity of Common NSAIDs Generally, the more selective for COX-1, the more serious side-effects appear http://elfstrom.com/arthritis/nsaids/actions.html
Slide 8 - Prostaglandin, Leukotriene, and Thromboxane Synthesis Eric Niederhoffer SIU-SOM Pathway overview Prostaglandin receptors Pathway details Differential actions of cyclooxygenases COX-1 and COX-2 comparison COX-1 specificity of common NSAIDs Tissue comparison Pathway Overview Linoleic acid Thromboxane A2 synthase Lipoxygenase Prostaglandin H2 synthase Prostaglandin Receptors http://www.caymanchem.com/app/template/scientificIllustrations%2CIllustration.vm/illustration/2018/a/z Pathway Details Phospholipase A2 (or PLC) Membrane phospholipids Cyclooxygenase O2 Arachidonic acid PGG2 PGH2 PG hydroperoxidase 2GSH GSSG NSAIDS (aspirin) Anti-inflammatory steroids Glucocorticoids (mediated by lipocortin-Ca2+) IL-1R IL-1 (inflammation) PGI2 (PC) PGE2 PGI2 synthase PGE2 synthase PGD2 PGF2a PGD2 synthase PGF2 synthase PGH2 synthase LTD4 LTE4 LTB4 LTC4 Glutathione S-transferase LTA4 TXA2 TXA2 synthase PGJ2 Differential Actions of Cyclooxygenases NSAIDs COX1 Constitutive COX2 Inducible Inflammatory Endothelial integrity Vascular patency Gastric mucosal integrity Bronchodilation Renal function Platelet function Inflammation Unwanted side-effects Therapeutic anti-inflammatory effects PGE2 PGF2a Proteases PGI2 PGE2 TXA2 Housekeeping COX-1 and COX-2 Comparison http://elfstrom.com/arthritis/nsaids/actions.html COX-1 Specificity of Common NSAIDs Generally, the more selective for COX-1, the more serious side-effects appear http://elfstrom.com/arthritis/nsaids/actions.html Tissue Comparison Ar Ar Ar Brain/nerve Vascular beds Synovial cells PGH2 PGH2 PGH2 PGF2a PGD2 PGE2 PGI2 (PC) PGE2 PGI2 (PC) PGE2 TXA2 So what would happen if we gave a patient a large dose of aspirin or Coxib to reduce inflammation/pain in these tissues?
Slide 9 - Prostaglandin, Leukotriene, and Thromboxane Synthesis Eric Niederhoffer SIU-SOM Pathway overview Prostaglandin receptors Pathway details Differential actions of cyclooxygenases COX-1 and COX-2 comparison COX-1 specificity of common NSAIDs Tissue comparison Pathway Overview Linoleic acid Thromboxane A2 synthase Lipoxygenase Prostaglandin H2 synthase Prostaglandin Receptors http://www.caymanchem.com/app/template/scientificIllustrations%2CIllustration.vm/illustration/2018/a/z Pathway Details Phospholipase A2 (or PLC) Membrane phospholipids Cyclooxygenase O2 Arachidonic acid PGG2 PGH2 PG hydroperoxidase 2GSH GSSG NSAIDS (aspirin) Anti-inflammatory steroids Glucocorticoids (mediated by lipocortin-Ca2+) IL-1R IL-1 (inflammation) PGI2 (PC) PGE2 PGI2 synthase PGE2 synthase PGD2 PGF2a PGD2 synthase PGF2 synthase PGH2 synthase LTD4 LTE4 LTB4 LTC4 Glutathione S-transferase LTA4 TXA2 TXA2 synthase PGJ2 Differential Actions of Cyclooxygenases NSAIDs COX1 Constitutive COX2 Inducible Inflammatory Endothelial integrity Vascular patency Gastric mucosal integrity Bronchodilation Renal function Platelet function Inflammation Unwanted side-effects Therapeutic anti-inflammatory effects PGE2 PGF2a Proteases PGI2 PGE2 TXA2 Housekeeping COX-1 and COX-2 Comparison http://elfstrom.com/arthritis/nsaids/actions.html COX-1 Specificity of Common NSAIDs Generally, the more selective for COX-1, the more serious side-effects appear http://elfstrom.com/arthritis/nsaids/actions.html Tissue Comparison Ar Ar Ar Brain/nerve Vascular beds Synovial cells PGH2 PGH2 PGH2 PGF2a PGD2 PGE2 PGI2 (PC) PGE2 PGI2 (PC) PGE2 TXA2 So what would happen if we gave a patient a large dose of aspirin or Coxib to reduce inflammation/pain in these tissues? Review Questions How are prostaglandins, leukotrienes, and thromboxanes synthesized (substrates, enzymes, cofactors)? What is the nomenclature for prostaglandin receptors? How do NSAIDs work? How do steroids work? What are the important characteristics of COX-1 and COX-2?