Non-Steroidal Anti-Inflammatory Drugs

Question 1

non-steroidal anti-inflammatory drugs work primarily by inhibiting ______________________________________________

Answer 1

cyclooxygenase enzymes and reducing production of prostaglandins

Question 2

what are the effects of non-steroidal anti-inflammatory drugs?

Answer 2

antipyretic
anti-inflammatory
analgesic

Question 3

what is the unifying mechanism of action of non-steroidal anti-inflammatories?

Answer 3

inhibit cyclooxygenases (COX) and decrease prostanoid (prostaglandin) concentrations

Question 4

what are the functions of COX and PGs in the kidneys?

Answer 4

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

Question 5

what does cyclooxygenase-1 generally lead to?

Answer 5

production of prostaglandins that mediate homeostatic functions

Question 6

what do thromboxanes stimulate?

Answer 6

vasoconstriction and platelet aggregation

Question 7

what do prostaglandins involved in the inflammatory response do?

Answer 7

vasodilation
pain
swelling
impaired cellular function

Question 8

what cells produce PGE2?

Answer 8

inflammatory cells

Question 9

what does PGE2 do?

Answer 9

dilates vascular smooth muscle
pyretic agent
sensitizes nociceptors
spinal cord transmission of pain signals

Question 10

are prostaglandins involved in pain transmission?

Answer 10

yes- central transmission of pain
upregulate pain pathways- primarily mechanical pain

Question 11

what needs to happen for an NSAID to have a central effect?

Answer 11

NSAID must get into the CSF

Question 12

peripheral inflammation sensitizes the animal to __________________________

Answer 12

mechanical and other pain

Question 13

what helps mitigate central sensitization?

Answer 13

pre-emptive inhibition of peripheral inflammation

Question 14

what happens after bacterial products enter the systemic circulation (endotoxins)?

Answer 14

immunosuppression
vasodilation, increased vascular permeability, decreased perfusion
systemic effects (fever, decreased inotropy, metabolic abnormalities)
microvascular thrombosis

Question 15

what does septic shock ultimately lead to?

Answer 15

multi-organ failure

Question 16

do non-steroidal anti-inflammatory drugs have additional effects above COX inhibition?

Answer 16

some may have: differences in response and profile

Question 17

what do the primary clinical benefits and adverse effects of non-steroidal anti-inflammatory drugs result from?

Answer 17

reducing prostanoid production and thus their effects

Question 18

what drug is approved for dogs that you should not use due to toxicity?

Answer 18

phenylbutazone

Question 19

what drugs are approved in dogs in the COX-2 selective group?

Answer 19

deracoxib
firocoxib
meloxicam
robenacoxib

Question 20

are non-steroidal anti-inflammatory drugs protein-bound?

Answer 20

yes- highly

Question 21

how are non-steroidal anti-inflammatory drugs metabolized?

Answer 21

cytochrome P450 and glucuronosyltransferase

Question 22

what should you keep in mind with non-steroidal anti-inflammatory drugs in cats?

Answer 22

lack certain UDP-GT enzymes
prolonged half life for aspirin
do not use acetominophen

Question 23

where do NSAIDs tend to stay?

Answer 23

in inflammatory exudate: anti-inflammatory effects may be longer than suggested by their half life

Question 24

when are NSAIDs most effective?

Answer 24

trauma
chemical
“infectious” inflammation

Question 25

what provides the pain relief associated with NSAIDs?

Answer 25

combination of anti-inflammatory effects and central analgesic effects

Question 26

are COX-2 selective NSAIDs more effective than non-selective NSAIDs as anti-inflammatory analgesics?

Answer 26

no, not as a class

Question 27

why do we use NSAIDs for their antipyretic effect?

Answer 27

reduce fever that is dangerously high (small animal primarily) improve attitude and appetite (bovine and equine mostly)

Question 28

do some NSAIDs improve clinical parameters in patients with septic shock?

Answer 28

yes may not be worth risk due to poor perfusion

Question 29

what drug is used to treat septic shock in cows and horses?

Answer 29

flunixin

Question 30

in which cancer are NSAIDs most commonly used?

Answer 30

transitional cell carcinoma in dogs

Question 31

what are the pharmacological toxicities of NSAIDs?

Answer 31

gastroenteropathies renal toxicity anti-platelet effects reproductive effects (delay parturition) delayed soft tissue healing (and bone healing if long-term)

Question 32

what is a host-dependent adverse effect we see with carprofen?

Answer 32

hepatitis

Question 33

current evidence suggests that inhibition of ___________________ required for ulceration

Answer 33

both COX1 and COX2

Question 34

what does COX-2 selectivity do with gastroduodenal irritation, ulceration, and gastric acid disturbances?

Answer 34

decreases it not with small intestine ulcers

Question 35

which species is more susceptible to small intestine ulcers?

Answer 35

canines: enterohepatic recirculation likely role

Question 36

inhibition of ________ is most important in inflammation and associated pain

Answer 36

COX-2

Question 37

what can happen in the colon with NSAIDs?

Answer 37

colitis especially right dorsal colitis in horses

Question 38

do corticosteroids interact with NSAIDs?

Answer 38

yes: marked increase in risk of adverse effects

Question 39

what are the risk factors of renal toxicity with NSAIDs?

Answer 39

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

Question 40

in what does cyclooxygenase-1 play an important role in homeostatic functions?

Answer 40

gastric mucosa kidneys platelets vascular endothelium

Question 41

what are the homeostatic functions of prostanoids?

Answer 41

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

Question 42

what cells produce prostacyclin (PGI2)?

Answer 42

endothelial cells and vascular smooth muscle cells

Question 43

what is pain caused by?

Answer 43

prostaglandins nerve growth factor leukotrienes bradykinin histamine 5-HT, substance P

Question 44

are most of the NSAIDs in small animal COX-2 selective?

Answer 44

yes phenylbutazone is not- toxic

Question 45

how long are the half-lives of most NSAIDs?

Answer 45

relatively short

Question 46

what are the anti-inflammatory indications?

Answer 46

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

Question 47

are NSAIDs such as flunixin an effective analgesic in horses with colic?

Answer 47

yes

Question 48

who is flunixin used to treat septic shock in?

Answer 48

cows horses

Question 49

what are some intrinsic toxicities with NSAIDs?

Answer 49

acid-base imbalance direct gastrointestinal irritation maybe hepatopathies and renal toxicity

Question 50

what are some preventative options for ulceration?

Answer 50

omeprazole misoprostol sucralfate

Question 51

do COX-2 selective agents display a decreased risk of renal toxicity?

Answer 51

no

Question 52

in whom do blood dyscrasias occur?

Answer 52

people: concern over food residues of phenylbutazone, dipyrone

Question 53

with what drug do we see idiosyncratic hepatitis?

Answer 53

carprofen probably robenacoxib

Question 54

what are some drug interactions of NSAIDs?

Answer 54

corticosteroids do not combine NSAIDs furosemide aminoglycosides