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56 Cards in this Set
- Front
- Back
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What are the 5 cardinal signs of inflammation?
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1) Swelling
2) Redness 3) Heat 4) Pain 5) Loss of function |
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What is the pathogenesis of osteoarthritis?
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Damage to chondrocytes and/or synovial cells--> inflammation of synovial membrane and articular cartilage, recruitment of leukocytes --> prostaglandins, leukotrienes, superoxides, proteolytic enzymes ---> increased viscosity of synovial fluid, damage to joint structures, inflammation---> positive feed back
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What produces the proteolytic enzymes associated with inflammation?
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Leukocyte degranulation and lysis
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What usually results in the death of a cow with shipping fever?
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The inflammation in the lungs results in tons of neutrophils invading the lungs --> fibrin--> abscesses in lungs--> inflammation--> death
*Positive feedback loop |
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What produces leukotrienes and prostaglandins?
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Injury to lipid membrane--> phospholipase activation--> release of arachidonate---->
1. If catalyzed by cyclo-oxygenase--> prostaglandins 2. If catalyzed by lipoxygenase ---> leukotrienes |
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What's are the 3 effects of leukotriene release?
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1) Chemotaxis
2) Leukocyte aggregation 3) Degranulation |
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What are the 2 principal targets of most anti-inflammatories?
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Cyclo-oxygenase
LIpoxygenase |
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What are the 2 effects of thromboxane release?
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1) Vasoconstriction
2) Platelet aggregation |
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What prostaglandins cause vasoconstriction?
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PGF2alpha
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What prostaglandins cause vasodilation?
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PGE2 & PGI2
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What are 2 effects of all prostaglandins during inflammation?
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1) Pyresis
2) Pain sensitization |
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What is the effect of proteolytic enzyme release during inflammation?
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Destruction of collagen, gelatin matrix, glycosaminoglycans (important in joint fluid), and proteoglycans
-Breaking apart the matrix in joints & cartilage |
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What are the 2 effects of superoxide release during inflammation?
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1) Lipid peroxidation
2) Tissue destruction |
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What is the *primary mechanism of action of non-steroidal anti-inflammatory drugs?
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Inhibition of cyclo-oxygenase.
-Agents vary w/ regards to COX-1 vs. COX-2 inhibition |
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What is an example of a dual blocker (cyclo-oxygenase & lipoxygenase)?
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Tepoxalin
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What is the effect of cyclo-oxygenase 1 (COX 1) release?
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Production of cytoprotective prostaglandins involved in reduction of gastric acid secretion and maintenance of adequate renal blood flow
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What is the effect of cyclo-oxygenase 2 (COX 2) release?
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Production of proinflammatory prostaglandins involved in pathologic effects associated w/ osteoarthritis
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What happens if you inhibit COX 1?
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Lack of renal perfusion
Increased gastric acid |
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Cyclo-oxygenase ____ release is constitutive, compared to cyclo-oxygenase ____ release is induced.
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COX1 =constitutive
COX2=induced |
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What is COX3?
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Located in brain, probably the target for acetaminophen which only has central actions
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What is the prototype NSAID?
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Aspirin
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Research developments have focused on development of _______ and dual blockers (*tepoxalin).
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Preferential COX-2 inhibitors
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What are 4 conventional NSAIDs?
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1) Aspirin
2) Phenylbutazone 3) Flunixin 4) Ketoprofen |
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What are 4 COX-1 sparing NSAIDs?
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1) Carprofen
2) Deracoxib 3) Meloxican 4) Etodolac |
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What is the big difference b/w conventional NSAIDs and COX-1 sparing NSAIDs?
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COX1/COX2 ratio- COX-1 sparing drugs are going to have a much higher ratio (greater than 1) because it takes a lot higher concentrations to inhibit COX-1, whereas conventional NSAIDs have a ratio below 1 because inhibit COX1 at much lower concentrations
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What are the 2 "other" mechanisms of action of non-steroidal anti-inflammatory drugs?
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1) Alter cellular and humoral immune responses
2) Partition into inflammatory cell membranes deminishing a variety of functions, including release of superoxides and lysosomal enzymes, neutrophil adhesion, chemotaxis |
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What are the 3 pharmacological actions of NSAIDs?
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1) Anti-inflammatory effect
2) Antipyretic effect 3) Analgesic effect |
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True or false. It usually doesn't take very high doses to achieve the anti-inflammatory effect of NSAIDs.
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False, usually accomplished at higher doses, but is drug specific
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What is the antipyretic effect of NAIDs?
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Resets the hypothalmic temperature control mechanism
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How do NSAIDs accomplish the analgesic effect?
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Direct central and indirect peripheral effects
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When are NSAIDs an appropriate therapy for pain control?
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When it's a pain of low to moderate intensity arising from integumental structures
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What is oral absorption of NSAIDs like?
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Most are organic acids and are mainly unionized at gastric pH so are well absorbed (high bioavailability)
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How does hypoalbuminemia affect NSAID concentrations?
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Most NSAIDs are highly plasma protein bound so the free/active concentrations increase w/ hypoalbuminemia and/or competition w/ other drugs
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How are NSAIDs eliminated?
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Conjugation usually involves glucoronidation.
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Why are NSAIDs present in the interstitium longer than anticipated based on half life?
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Because in areas of inflammation there's increased permeability of the vasculature so are in the interstitium bound to albumin which results in retention of the drug in the interstitium for a period longer than anticipated based on half life
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What animal has to have a longer dosage interval with NSAIDs? Why?
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Cats, are deficient in glucoronidation-the elimination process for NSAIDs
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What metabolic pathways are deficient in pigs and dogs?
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Pigs: sulfation
Dogs: acetylation |
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What is the half life of aspirin in a dog? Cat?
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Dog: 7.5 hours
Cat: 45 hours! |
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How often do you give a cat aspirin for anti-inflammatory properties? Analgesic/antipyretic?
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Analgesic/antipyretic: 48 h
Anti-inflammatory: 24 h (at higher dose) -Compared to 12 and 18 h (anti-inflamm) for dogs! |
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What are the 6 signs related to NSAID toxicity?
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1) GI irritation & ulceration
2) Nephrotoxicity 3) Cardiovascular 4) Hepatotoxicity 5) Acid-base disturbances 6) Coagulation deficiencies |
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What NSAID is hepatotoxicity most likely in?
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Carprofen
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What are the 2 most important side effects of NSAIDs?
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1) GI irritation & ulceration
2) Nephrotoxicity |
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Why do NSAIDs cause GI irritation and ulceration?
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-Increased acid production because of COX1 inhibition
-Less mucous production bc of prostaglandin inhibition |
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Why do NSAIDs cause nephrotoxicity?
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Blocking COX1 results in a lack of renal perfusion
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What is the worse human anti-inflammatory animals can get? Why?
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Tylenol because it is metabolized into a reactive metabolite that causes massive liver damage
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Why does a gastric ulcer bleed worse in an animal on NSAIDs?
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Prevents clotting
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Why do animals have a higher risk of heart attacks when on NSAIDs?
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Some COX2 products have important effects in maintaining vasodilation and inhibiting platelet aggregation, so inhibiting these you get vasoconstriction and platelet aggregation--> thrombosis--> higher rate of heart attacks
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What is the structure of polysulfated glycosaminoglycan?
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Repeating disaccharide units
-Principally chondroitin sulfate |
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What are the 3 mechanisms of action of polysulfated glycosaminoglycans?
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1) Promotes synthesis of cartilage matrix components (collagen, proteoglycans)
2) Inhibits catabolic enzymes, including neutral metalloproteases 3) Inhibition of PGE2 synthesis -Improve and maintain viscosity and lubricating properties of joints but also prevent formation of inflammatory mediators |
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What are the 2 pharmacological activities of polysulfated glycosaminoglycans?
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1) Inhibits inflammation and degradation of joint tissues
2) Improves viscosity of syovial fluid |
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What toxicity is associated with polysulfated glycosaminoglycans?
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Rare hypersensitivity and bleeding disorders
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What is the postulated MOa of glucosamine and chondroitin sulfate?
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Inhibits degradative enzymes and stimulates chondrocyte and synoviocyte metabolism
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What is cosequin?
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Glucosamine & chondroitin sulfate-not FDA approved
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What are the 4 mechanisms of action of DMSO?
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1) Scavenges oxygen radicals
2) Stabilizes membranes 3) Blocks pain conduction 4) Blocks hyaluronic acid polymerization, fibroblast proliferation |
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What are 3 toxicities associated with DMSO usage?
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1) Opacity of the lens
2) Slight cholinesterase inhibition 3) Local irritation |
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Describe the absorption, distribution and metabolism of DMSO.
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Rapid absorption
Extensive distribution Rapid metabolism |
