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102 Cards in this Set
- Front
- Back
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What are some general causes of inflammation? |
Toxins Trauma Damage to cell membranes (via microorganisms) |
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Physiologically, what occurs with inflammation? |
Local transient vasodilation Capillary leakage Increased WBCs & phagocytes Tissue degredation & fibrosis |
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What do leukocytes produce during inflammation? |
Lysozomal enzymes Histamine, seratonin, platelet activating factor Oxygen free radicals Cytokines (interleukins, TNF) Eicosanoids |
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Eicosanoids are derived from _________ |
Arachidonic acid |
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What is the effect of capillary widening during inflammation? |
Increased blood flow |
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What is the effect of increased capillary permeability during inflammation? |
Release of fluid |
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What is the systemic response to inflammation? |
Fever Proliferation of WBCs |
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What are the cardinal signs of inflammation? |
Heat Redness Tenderness Swelling Pain |
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The main action of NSAIDS is to block ______ |
Arachidonic acid pathway via cyclooxygenase enzyme Blocks the conversion of AA to prostaglandin PGG2 Also inhibits thrombosis at low doses |
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General Clinical Effects of NSAIDS |
Analgesia Antipyresis Anti-inflammatory |
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How does cell membrane damage cause arachidonic acid production? |
Release of membrane membrane phospholipds Phospholipase A2 generates arachidonic acid |
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COX converts ________ to ___________ |
Arachidonic acid to prostaglandin G2 |
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Which COX enzyme is mostly effected by NSAIDS?
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2>1 With chronic inflammation, COX2 is increased |
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Most phospholipds are made of.... |
Omega 6 fatty acids |
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Where do steroids block the inflammation cascade? |
Phospholipase A2 |
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NSAID Effect on Leukotriens |
Does NOT block, not really considered important when treating inflammation |
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NSAID Groups |
Salicylate/carboxylate acid derivatives Propionic acids Oxicams Fenamates Pyrazolones/Enolic acids |
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_______ is the only NSAID to irreversibly bind COX enzymes |
Salicylate/carboxylate acid derivatives (aspirin)
Binds platelets for up to 2 weeks - inhibits their function |
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NSAID Metabolism |
Hepatic metabolism Conjugated metabolites excreted in urine Extensive enterohepatic circulation - can increase the half life |
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Geriatric patients clear less _________ drug |
Unbound |
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Pediatric patients have __________ the volume of unbound drug |
Double |
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NSAID Half Life |
Low plasma half-life, but longer effect on the cell Anything that decreases blood flow increases the half life |
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COX1 vs COX2 |
Cox1 Consituative, necessary for normal homeostasis Responsible for acute inflammation Cox2 Inducible form responsible for chronic inflammation |
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Which cells can produce COX2? |
Moncytes Fibroblasts Synoviocytes Chondroblasts |
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Damaged cell membranes release ________ |
Fatty acids from cell membrane phospholipases |
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Non-selective NSAIDS effect..... |
COX1 & COX2 at the same levels |
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___________ primarily targets COX2 |
Selective NSAIDS |
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COX1 activates ________ prostaglandins while COX2 activates _________ prostaglandins |
COX1 - Constitutive prostaglandins COX2- Inducible prostaglandins |
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Which cells can produce COX1? |
All cells except RBCs |
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How can NSAIDS affect neoplasia? |
Can slow down the process by blocking prostaglandins - antitumor effects |
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Effects of Prostaglandin D2 |
Vasodilation Bronchoconstriction Regulates body temp while sleeping Development of the male repro system |
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Effects of Prostaglandin I2 (prostacyclin) |
Inhibits platelet aggregation Vasodilation |
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Prostaglandin I2 is produced by the ...... |
Vascular wall |
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Effects of Prostaglandin F2a |
Leutolyss of CL Induction of labor/abrotifacient Contraction |
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Effects of Thromboxane A2 |
Potent vasoconstrictor Stimulates platelet aggregation |
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Thromboxane A2 is produced by...... |
Damaged endothelium Platelets |
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Aspirin irreversibly blocks _________ release from platelets |
Thromboxane A2 |
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Effects of Prostaglandin E2 |
Fever Potent vasodilator Bone resorption Smooth muscle relaxation Pain Gastric mucosa vasodilation, bicarb secretion, mucus secretion, epithelilization |
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Does aspirin effect COX1 or COX2? |
COX1 COX2 at very high doses |
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NSAIDS modulate the effects of which immune cell? |
T-cell function
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Why are NSAIDS hard to use in cats? |
Poor ability to glucuronidate drugs - UDP-glucuroninosyl-transferase enzyme Highly variable half-life due to prolonged metabolism by the liver |
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NEVER give cats which NSAID? |
Acetaminophen |
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How should you monitor prior to prescribing NSAIDS? (Especially important in cats) |
Physical exam & history Blood work Blood pressure Urinalysis - Protein:creatine ratio - Specific gravity - Sediment cytology |
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What is the most common side effect of NSAIDS in horse? |
Renal necrosis Also colitis and gastric ulcers |
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General NSAID Side Effects
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Renal failure GI ulceration/perforation Delayed bone healing Hypovolemia/hypotension Hepatotoxicity Renal hypoperfusion |
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Never ever, ever give an NSAID along with ________ |
Steroids/glucocorticoids Requires a week washout period |
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NSAID Drug Interactions |
Steroids Nephrotixic drugs Anticoagulant ACE inhibitors Diuretics Beta blockers |
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When changing to another type of NSAIDS.... |
Requires a 2 week washout period Also good to put the animal on a gastro-protectant (Ex: omeprazole) |
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ACE Inhibitors Interaction with NSAIDS |
Ace inhibitor effects are decreased with NSAIDs |
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Diuretics Interaction with NSAIDS |
Dehydration increases the risk of renal damage |
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Beta Blockers Interaction with NSAIDS |
Beta blocker effects decreased with NSAIDS |
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How can you prevent ulceration with NSAIDS? |
Do not administer if you suspect an ulcer is present! Pre/concurrent treatment with gastro-protectants - Misoprostol - Omeprazole - High dose famotidine - Sucralfate |
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What are the signs of gastric ulceration? |
Decreased appetite Salivation Regurgitation/burping Vomiting Diarrhea Collapse shock Death If you can catch it before vomiting, you can treat it medically with good success - tell owners the signs of GI ulceration! |
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Hematopoietic Side Effects of NSAIDS |
Platelet inhibition Thrombosis (with COX2 selective drugs) |
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How do NSAIDS cause thrombosis? |
Decreased prostacyclins |
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Neutrophil Side Effects of NSAIDS |
Inhibits neutrophil adhesion - Good: Antitumor effect - Bad: Limits immune response |
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NSAIDS inhibit _________ of leukocytes Which drug has the most potent effect on this? |
Inhibits movement of leukocytes Flunixin meglumine is the most potent inhibitor |
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SERS |
Systemic Inflammatory Response Syndrome Really hard to come back from this, may lead to death without strong intervention |
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Which NSAID can inhibit transitional cell carcinoma in dogs? |
Piroxicam |
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NSAID Effects on Bone & Articular Cartilage |
Inhibits bone repair & remodeling Decreased proteoglycan synthesis - aspirin Chondrocyte death - phenybutazone Chondroprotective - naproxen. piroxicam |
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NSAID Renal Side Effects |
Inhibits renal vasoconstriction as a response to hypovolemia via inhibition of prostaglandins Chronic NSAID usage can result in analgesic nephropathy |
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How should you monitor patients on NSAIDS during treatment? |
Periodic physical exam & blood work Adjusting dose to body weight & condition Calibrate to the lowest dose of drug at the lowest frequency to treat the condition |
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Fibrocoxib MOA? Why is it great? Why does it suck? Dosing? |
Selective COX2 (veterinary specific) Works very fast, but high incidence of side effects SID dosing |
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Fibrocoxib given along with phenalbutazone can cause..... |
Renal failure |
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Carprofen can only be used in what species? |
Dogs |
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Carprofen MOA |
Selective COX2 inhibitor |
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Carprofen Side Effects |
Hepatotoxicity (acute hepatic necrosis) Especially in labradors & geriatric patients |
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Piroxicam MOA |
Selective COX2 inhibitor (very selective) Used as an adjuctive therapy for neoplasia |
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Why isn't piroxicam used more often? |
8% risk of serious side effects |
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Deracoxib MOA |
Selective COX2 inhibitor |
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Deracoxib is especially good to treat ________ pain |
Musculoskeletal |
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Deraxocib Dosing |
SID |
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Daracxocib can be used in which species? |
Dogs |
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Meloxicam can be used in which species? |
Dogs Legally prohibited in cats, but is done sometimes - have owners signs a form! |
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Meloxicam Dosing |
Injection or oral (SID) |
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Which NSAID is especially good for chronic analgesia? |
Meloxicam (not as effective for acute pain vs opiods) Also: robenacoxib, piroxicam Can give once the patient is stable & eating |
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Which NSAID used for chronic analgesia has the lowest incidence of GI side effects? |
Robenacoxib (10%) |
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Robenacoxib MOA |
COX-2 selective inhibitor |
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Robenacoxib can be used in which species? For how long? |
Cats - excellent analgesia with short IV time Oral approved fo up to 3 days (but is often used for longer periods) |
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Robenacoxib Side Effects |
Vomiting Gastroduodenal ulceration (consider use of omeprazole) No toxicity identified - has a very short half-life |
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Robenacoxib MOA |
Selective COX2 inhibitors in central compartment |
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Robenacoxib Elimination |
Biliary (less renal side effects) |
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Phenylbutazone is used in which species? |
Horses |
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Phenylbutazone is used to treat..... |
Acute inflammation - improves lameness & improves weight bearing with navicular disease Does not block thermal or acute nociceptive paie |
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Phenylbutazone Dosing |
Oral - SID to BID |
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Phenybutazone Effects of Overdosing |
Anorexia Neutropenia Hypoproteinemia |
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How can phenylbutazone cause death in horses? |
Gastric ulceration Renal necrosis Vascular thrombosis |
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Which NSAID has a ceiling effect? |
Phenylbutazone Drug binds to receptor and giving more drug does not elicit additional response |
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Flunixin Meglumine is used in which species? |
Horses dogs |
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Flunixin meglumine is used to treat..... |
Visceral pain - improved lameness Endotoxemia (binds endotoxins) |
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Banamine is the trade name of.... |
Flunixin megluimine |
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What can happen if you give flunixin meglumine IM? |
Clostridial myonecrossi |
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Acetominopen MOA |
Interferes with PGH2 & PGG2 intermediates NOT a COX inhibitor |
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Acetaminophen is sometimes used in which species? |
Dogs Good if you can't use an NSAID |
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Ketoprofen is used in which species? |
Horses High risk of death is small animals |
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Which is better at improving lameness: bute or ketoprofen? |
Bute |
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Ketoprofen Administration |
IV |
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What do you need to monitor if you give a horse ketoprofen? |
Total protein & albumin Decreases are a sign of perforation |
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Ketoprofen Side Effects |
Right dorsal colitis |
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Dog chews of _____ are often given to horses |
Firocoxib Cheaper than the equine paste |
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What are commonly supplemented omega 3 fatty acids? |
Eicosapentanoic acid Docosahexanoic acid |
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Omega 2 fatty acids are often used to treat..... How does it work? |
Osteoarthritis or other cases of chronic inflammation - often in conjunction with NSAIDs Reduction of arachadonic acid production via omega 6 fatty acids |
