Non-Steroidal Anti-Inflammatory Drugs Flashcards
non-steroidal anti-inflammatory drugs work primarily by inhibiting ______________________________________________
cyclooxygenase enzymes and reducing production of prostaglandins
what are the effects of non-steroidal anti-inflammatory drugs?
antipyretic
anti-inflammatory
analgesic
what is the unifying mechanism of action of non-steroidal anti-inflammatories?
inhibit cyclooxygenases (COX) and decrease prostanoid (prostaglandin) concentrations
what are the functions of COX and PGs in the kidneys?
PGs influence renal hemodynamics, body water and salt balance, and inflammatory processes
COX-1 and COX-2 contribute to normal function
both play a role in maintaining normal blood flow during low blood pressure
what does cyclooxygenase-1 generally lead to?
production of prostaglandins that mediate homeostatic functions
what do thromboxanes stimulate?
vasoconstriction and platelet aggregation
what do prostaglandins involved in the inflammatory response do?
vasodilation
pain
swelling
impaired cellular function
what cells produce PGE2?
inflammatory cells
what does PGE2 do?
dilates vascular smooth muscle
pyretic agent
sensitizes nociceptors
spinal cord transmission of pain signals
are prostaglandins involved in pain transmission?
yes- central transmission of pain
upregulate pain pathways- primarily mechanical pain
what needs to happen for an NSAID to have a central effect?
NSAID must get into the CSF
peripheral inflammation sensitizes the animal to __________________________
mechanical and other pain
what helps mitigate central sensitization?
pre-emptive inhibition of peripheral inflammation
what happens after bacterial products enter the systemic circulation (endotoxins)?
immunosuppression
vasodilation, increased vascular permeability, decreased perfusion
systemic effects (fever, decreased inotropy, metabolic abnormalities)
microvascular thrombosis
what does septic shock ultimately lead to?
multi-organ failure
do non-steroidal anti-inflammatory drugs have additional effects above COX inhibition?
some may have: differences in response and profile
what do the primary clinical benefits and adverse effects of non-steroidal anti-inflammatory drugs result from?
reducing prostanoid production and thus their effects
what drug is approved for dogs that you should not use due to toxicity?
phenylbutazone
what drugs are approved in dogs in the COX-2 selective group?
deracoxib
firocoxib
meloxicam
robenacoxib
are non-steroidal anti-inflammatory drugs protein-bound?
yes- highly
how are non-steroidal anti-inflammatory drugs metabolized?
cytochrome P450 and glucuronosyltransferase
what should you keep in mind with non-steroidal anti-inflammatory drugs in cats?
lack certain UDP-GT enzymes
prolonged half life for aspirin
do not use acetominophen
where do NSAIDs tend to stay?
in inflammatory exudate: anti-inflammatory effects may be longer than suggested by their half life
when are NSAIDs most effective?
trauma
chemical
“infectious” inflammation
what provides the pain relief associated with NSAIDs?
combination of anti-inflammatory effects and central analgesic effects
are COX-2 selective NSAIDs more effective than non-selective NSAIDs as anti-inflammatory analgesics?
no, not as a class
why do we use NSAIDs for their antipyretic effect?
reduce fever that is dangerously high (small animal primarily)
improve attitude and appetite (bovine and equine mostly)
do some NSAIDs improve clinical parameters in patients with septic shock?
yes
may not be worth risk due to poor perfusion
what drug is used to treat septic shock in cows and horses?
flunixin
in which cancer are NSAIDs most commonly used?
transitional cell carcinoma in dogs
what are the pharmacological toxicities of NSAIDs?
gastroenteropathies
renal toxicity
anti-platelet effects
reproductive effects (delay parturition)
delayed soft tissue healing (and bone healing if long-term)
what is a host-dependent adverse effect we see with carprofen?
hepatitis
current evidence suggests that inhibition of ___________________ required for ulceration
both COX1 and COX2
what does COX-2 selectivity do with gastroduodenal irritation, ulceration, and gastric acid disturbances?
decreases it
not with small intestine ulcers
which species is more susceptible to small intestine ulcers?
canines: enterohepatic recirculation likely role
inhibition of ________ is most important in inflammation and associated pain
COX-2
what can happen in the colon with NSAIDs?
colitis
especially right dorsal colitis in horses
do corticosteroids interact with NSAIDs?
yes: marked increase in risk of adverse effects
what are the risk factors of renal toxicity with NSAIDs?
high dose, prolonged duration
patients with prostaglandin-dependent glomerular blood flow: ischemic damage and decreased function
issues: surgery, compromised renal function
small animal probably more likely than equine
in what does cyclooxygenase-1 play an important role in homeostatic functions?
gastric mucosa
kidneys
platelets
vascular endothelium
what are the homeostatic functions of prostanoids?
inhibit acid secretion, stimulate mucous production, and enhance cell replication in GI tract
vasoconstriction or vasodilation
bronchoconstriction
stimulate smooth muscle contractions
lutolysis
aggregation (TXA2) or diaggregation of platelets
decrease intraocular pressure
what cells produce prostacyclin (PGI2)?
endothelial cells and vascular smooth muscle cells
what is pain caused by?
prostaglandins
nerve growth factor
leukotrienes
bradykinin
histamine
5-HT, substance P
are most of the NSAIDs in small animal COX-2 selective?
yes
phenylbutazone is not- toxic
how long are the half-lives of most NSAIDs?
relatively short
what are the anti-inflammatory indications?
most effective in trauma, chemical, or infectious inflammation
limited in immune-mediated
osteoarthritis/musculoskeletal disease: inflammatory and mechanical pain
laminitis
uveitis/other inflammatory eye disease
pneumonia
coliform mastitis
post-operative inflammation
are NSAIDs such as flunixin an effective analgesic in horses with colic?
yes
who is flunixin used to treat septic shock in?
cows
horses
what are some intrinsic toxicities with NSAIDs?
acid-base imbalance
direct gastrointestinal irritation
maybe hepatopathies and renal toxicity
what are some preventative options for ulceration?
omeprazole
misoprostol
sucralfate
do COX-2 selective agents display a decreased risk of renal toxicity?
no
in whom do blood dyscrasias occur?
people: concern over food residues of phenylbutazone, dipyrone
with what drug do we see idiosyncratic hepatitis?
carprofen
probably robenacoxib
what are some drug interactions of NSAIDs?
corticosteroids
do not combine NSAIDs
furosemide
aminoglycosides
