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12 Cards in this Set
- Front
- Back
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What are the 3 major effects of NSAIDs?
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-antipyretic
-analgesic -anti-inflammaory |
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How do NSAIDs exert their anti-pyretic effect?
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-the hypothalamus regulates normal bocy temperature
-prostaglandins increase the thermoregulatory set point -they are produced in the hypothalamus in response to interleukins released during the inflammatory process |
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How do NSAIDs exert their analgesic effect?
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-they decrease the production of prostaglandins such as PGE2 which enhances pain sensitization to proinflammatory mediators such as bradykinin, 5HT & substance P at nerve endings in the CNS and at site of inflammation
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What are the side effects of NSAIDs?
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GASTROINTESTINAL Side Effects
-are the most common -nausea, indigestion & vomiting, and with chronic use gastric ulceration -they suppress PGE2 which is cytoprotective to the gastric mucosa RENAL EFFECTS -the prostanoids PGE2 and PGI2 play a key role in regulation of renal blood flow and their Gs coupled receptors mediate vasodilation HAEMATOLOGIC EFFECTS -all NSAIDs are able to impair platelet activity by inhibiting thromboxane formation |
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Where is COX-1 and COX-2 expressed? Are they expressed all the time?
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COX-1
-constitutive enzyme expressed in most tissues COX-2 -an induced enzyme, responsible for prostanoid production in inflammatory cells in response to injury & inflammation -induced by IL-1 and endotoxins |
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Inhibition of which enzyme COX-1 or COX-2 causes the therapeutic effect? Which one causes the side effects?
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Inhibition of COX-2 is mainly responsible for the therapeutic effects of NSAIDs
-side effects are caused by suppression of COX-1 |
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Why can's we only inhibit COX-2?
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-COX-2 is constitutively present in several organs (e.g. blood vessels of the kidney, gut, and heart) where is synergizes with COX-1 in hemostasis, and it has been shown to increase risk of coronary vascular occlusion if it is inhibited alone
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What is the mechanism of action of Aspirin?
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-acetylates COX-1 and irreversibly inhibits it resulting in decreased prostaglanding synthesis as well as blockade of TXA2 production and its associated anti-coagulent efects
-also inhibits formation and release of kinins, and stabilizes lysosomes |
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What is the mechanism of action & side effects of paracetamol?
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-inhibits COX-3 in the CNS
SIDE EFFECTS: -narrow safety margin in cats -cats don't have Phase 2 glucoronidation mechanisms so the drug undergoes Phase 1 metabolism to hepatotoxic intermediates, leading to death by liver failure |
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How does Zubrin (Tepoxalin) act? What is the benefit of dual inhibitors?
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-it blocks COX & LOX
-Leukotrienes are powerful inflammatory mediators: Leukotriene B4 plays a central role in inflammation, increased microvascular permeability, and chemotactic properties involving neutrophil-endothelial adhesion and neutrophil aggregation and degranulation -leukotriene C4 & D4 are potent vasoconstrictors (renal vasoconstriction) -in the presence of NSAIDs the arachidonic acid pathway may be shunted to the LOX pathway which can cause renal vasoconstriction resulting in ischemia and renal failure -the dual inhibitors provide broad inflammatory effects with reduced renal & GI side effects |
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What is an example of a leukotriene inhibitor used in veterinary medicine?
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-cysteinyl leukotriene is important in the pathogenesis of asthma
-Zafirlukast and Montelukas are used off label for treatment of allergic pulmonary disease in cats |
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What is an example of a drug used for osteoarthritis?
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Polysulphated polysaccharide drugs (e.g. pentosan polysulphate "Cartrophen") in dogs and Polysulphated glycosaminoglycan ("Adequan") in horses
-retard the degredation of articular cartilage in osteoarthritis -stimulate synthesis of hyaluronan which is a component of synovial fluid in joints -hyaluronan also helps limit migration of leukocytes into joints, limits release of inflammatory mediators, and is a scavenger of ROS -inhibits PGE2 biosynthesis that is induced following joint injury -polysulphated polysaccharides have anticoagulent activity, leading to improved circulation to joints, and reduced joint pain |
