Lecture 26 4/30/24 Flashcards
What are the characteristics of acute inflammatory pain?
-soft tissue trauma or inflammation
-adaptive role in facilitating tissue repair
-hyperalgesia of injured area and surrounding tissue
What are the characteristics of chronic inflammatory pain?
-duration greater than 3-6 months
-offers no useful function or survival advantage
-affects quality of life and function
What are the steps of inflammatory response to tissue injury?
-release of inflammatory mediators
-vasodilation of local blood vessels
-granulocyte and monocyte migration
-swelling of tissue
Which inflammatory mediators are involved in inflammatory pain?
-histamine
-prostaglandins
-leukotrienes
-complement proteins (C3a/C5a/C5b67)
-IL-1, IL-6, TNF-alpha
-bradykinin
-fibrin/fibrinopeptides
How do steroids function?
by blocking PLA2
How do firocoxib and carprofen function?
by blocking COX-2
How do aspirin, flunixin, phenylbutazone, and meloxicam function?
by blocking both COX-1 and COX-2
How does ketoprofen function?
by blocking COX-1, COX-2, and 5-Lox
Why it important to know whether a drug impact COX-1 versus COX-2?
-COX-2 must be targeted to eliminate pain
-blocking COX-1 can impact the protective effects of prostaglandins
Where in the body is constitutive/non-inducible COX-2 found?
-kidneys
-GI tract
-lung
What is COX-2 involved in besides pain sensation?
-gene expression
-neoplasia
-bone modeling
Which type of NSAID is safer on the GI tract?
COX-2 selective NSAIDs
What are the pharmacokinetics of NSAIDs?
-well absorbed orally
-irritating if given IM or SQ
-lipophilic and low VD
-very high plasma protein binding
-enhanced penetration in inflammatory exudate
-mostly eliminated by liver
-may have extensive enterohepatic recycling
How do NSAIDs interact with furosemide?
-NSAIDs suppress early preload reducing effect
-can increase kidney toxicity
How do NSAIDs interact with ACE inhibitors?
-NSAIDS suppress some of the vasodilating effect
-can increase kidney toxicity
How do NSAIDs interact with fluoroquinolones?
may decrease seizure threshold
How do NSAIDs interact with aminoglycosides?
may increase renal toxicity
How do NSAIDs interact with antacids?
antacids can interfere with NSAID oral absorption
Why is it not recommended to mix steroids and NSAIDs?
leads to an additive effect for COX suppression based on PLA2 suppression upstream
What are the adverse effects associated with NSAIDs?
-GI ulcers
-kidney toxicity
What mediates the adverse effects seen with NSAIDs?
inhibition of protective prostaglandins
Why are cats more sensitive to NSAID toxicity?
lack of glucuronidation pathway
What are the characteristics of GI toxicity associated with NSAIDs?
-most common dose-limiting factor
-caused by protective prostaglandin suppression
-gastrointestinal adaptation typically occurs after a week of therapy
-must prevent toxicity in long-term use
What are the characteristics of renal toxicity associated with NSAIDs?
-due to reduced renal blood flow
-leads to decrease in glomerular filtration
-major concern in perioperative period, during hypotensive and hypovolemic conditions, in animals with congestive heart failure, and in animals with chronic renal disease
What are the characteristics of NSAID hematological and liver toxicity?
-can cause idiosyncratic hepatotoxicity
-should be avoided in animals with bleeding disorders
-should be avoided during surgery if hemorrhage is a potential concern
Why are NSAIDs often used preoperatively?
to reduce nociceptive windup
Which aspects of the nerve conduction pathway can NSAIDs impact?
-transduction
-modulation
-perception
What are the therapeutic uses of NSAIDs?
-acute trauma/surgery
-colic pain in horses
-pain from cancer
-osteoarthritis pain
-antithrombotic action
-cancer treatment
What are the general principles of NSAID use?
-use the lowest NSAID dose and frequency to achieve desired outcome
-watch for renal, hepatic, and coagulation disorders
-apply cytoprotective measures
-use preemptively when possible
What are the characteristics of aspirin?
-unspecific COX inhibitor
-oral bioavailability
-causes local GI irritation
-metabolized by liver via glucoronide conjugation
-considerable species differences in reabsorption
What are the uses of aspirin?
-analgesic
-anti-inflammatory
-antiplatelet
What are the adverse effects associated with aspirin?
-GI irritation and ulcer formation
-decreased clotting
-cartilage damage in arthritic dogs possible
How should NSAID adverse effects be managed?
-IV fluids
-gastroprotectant therapy
-monitoring of coagulation parameters
-use of washout period when switching NSAIDs
Why are cats at greater risk for NSAID adverse effects?
-deficiencies in metabolism
-decline in renal function with age
When using NSAIDs in cats, what must be considered?
-give with food when possible
-adjust dose to smallest amount possible
-short term use only
Which NSAIDs are approved for short term use in cats?
-meloxicam
-robenicoxib
Why can NSAIDs be dosed less frequently in camelids?
better oral absorption in camelids compared to other ruminants
What are the characteristics of grapiprant?
-not technically an NSAID
-PGE2-receptor antagonist
-blocks EP4 receptor, which mediates sensation of sensory neurons
-adverse effects are similar to other NSAIDs, but likely less toxic
