NSAIDs Flashcards
what are the non-pharmacological interventions to reduce inflammation
1) rest
2) heat/cold
3) weight loss
4) surgery
what are the 2 pharmacological interventions to reduce inflammation
1) NSAIDS
2) GLUCOCORTICOIDS
what is the mechanism of aspirin action
inhibition of prostaglandin synthesis
what is the oldest NSAID
aspirin
T/F NSAIDs are a family of chemically similar drugs
F
what are the three main benefits of all NSAIDs
1) anti-inflammatory
2) antipyretic
3) analgesic
prostaglandins are synthesized from ________________ by ______ and _____ enzymes
arachidonic acid; COX 1; COX 2
what are the 3 main prostaglandins
thromboxane, prostacyclin, other PGs
which of the COX enzymes is a housekeeping enzyme present at low levels in most tissues
COX1
what is COX2 important for
homeostasis of renal medulla and gastric mucosa
what is the role of:
1) thromboxane (TXA2)
2) other PGs (PGD2, PGE2, etc)
3) prostacyclin (PGI2)
1) made in platelets; promotes platelet aggregation
2) maintain tissue blood flow
3) inhibit platelet aggregation; vasodilation; gastric mucosa protection
what happens to the COX enzymes when there is inflammation
COX2 is locally upregulated -> prostacyclin produces vasodilation -> cardinal signs of inflammation
what are the signals of inflammation to the COX enzymes
plasma membrane damage or inflammatory mediator release
T/F most enzymes inhibit both COX1 and COX2
T
how to NSAIDS limit the cardinal signs of inflammation
block COX enzymes -> inhibition of production of prostaglandins -> no vasodilation (because prostacyclins blocked) -> no cardinal signs
a major benefit of NSAIDs is ___________ to ___________
reduction in blood flow; site of injury
what is the most common adverse effect of NSAIDs and why
gastric bleeding +/- ulceration; inhibition of prostaglandin synthesis means decreased secretion of bicarb/mucus, increased acid secretion and decreased blood flow to gastric mucosa (from prostacyclin and PGE2)
what are the 3 main adverse effects of NSAIDs
1) gastric bleeding
2) increased general tendency to bleed
3) renal medullary hypoxia and necrosis
What is the key takeaway of NSAIDs that preferentially target COX2
they produce fewer adverse GI affects as long as GI lesions are not already present (in which case they would be exacerbated)
T/F coxibs cause more bleeding
F; they cause less because platelet aggregation is not inhibited
what are the 4 shared pharmacokinetic properties of NSAIDs
1) weak acids
2) highy protein bound
3) hepatic metabolism (phase 2 conjugation)
4) variable elimination
T/F NSAIDs are associated with decreased uterine motility
T
what are some contraindications of NSAIDS
renal disease, gastric ulcers, hepatic disorders, hypoproteinemia, dehydration, cardiac disease
what is the shared clinical use of all NSAIDs
to reduce musculoskeletal and inflammatory pain
what is the only NSAID that irreversibly blocks COX enzymes
aspirin
what animals is aspirin approved for
cattle and horses
what is a consequence of aspirin binding irreversibly to COX enzymes
prolonged effects, even at low doses
in vitro, aspirin acts to inhibit, but in vivo it acts to inhibit
COX1 and COX2; mainly COX1
what is an adverse effect of aspirin and why
bleeding; inhibits COX1 therefore blocks thromboxane production
aspirin should not be used in what species and why
cats; deficient in glucuronide conjugation
what is the most popular NSAID for horses
phenylbutazone
phenylbutazone
- species
- enzymes blocked
- duration of action in target species
- therapeutic margin is narrow/wide
- formulations available
- horses
- COX1 and COX2
- 24h
- narrow
- oral and IV
aspirin:
- species
- enzymes blocked
- duration of action
- therapeutic margin is narrow/wide
- formulations available
- cattle and horses
- COX1 and COX2 in vitro, mainly COX1 in vivo
- 1h
- narrow
- oral only
what is an adverse effect of IM phenylbutazone
tissue necrosis
carprofen:
- approved species
- enzymes blocked
- therapeutic margin is narrow/wide
- dogs
- COX2
- narrow
what is a possible ADR associated with carprofen and what does this mean to us as vets
Type B idiosyncratic: acute hepatotoxicity; need to closely monitor
what is a benefit of carprofen compared to some other NSAIDs and why
less likely to see GI ulceration and perforation because it is selective to COX2
what are the most common adverse effects of carprofen
vomiting, diarrhea and anorexia
T/F carprofen can be used in cats
F
ketoprofen:
- approved species
- enzymes blocked
- therapeutic margin is narrow/wide
- half life
- approved in most species
- COX and LOX
- narrow
- 2h in serum but 24h in tissues
what is the most common adverse effect of ketoprofin
- vomiting
what NSAID inhibits leukotriene and bradykinin production in addition to inhibiting PG synthesis
ketoprofin
flunixin:
- approved species
- enzymes inhibited
- therapeutic margin is narrow/wide
- duration of action
- horses and cattle
- COX1 and COX2; leukocytes
- narrow
- 30h
meloxicam:
- approved species
- enzymes blocked
- therapeutic margin is narrow/wide
- duration of action in cats and in dogs
- dogs, cats, pigs, cattle
- both but more so COX2
- narrow but safer than other NSAIDs
- cats: 15h; dogs: 24h
what are the 3 coxibs
1) deracoxib
2) robenacoxib
3) firocoxib
what are the main concerns with excessive coxib use
1) renal papillary necrosis
2) pro-aggregatory effect with long-term use
T/F all coxibs can be used in dogs
T
which coxib is available for use in cats
robenacoxib
T/F if used properly, serious adverse effects of NSAIDs are uncommon
T
what is the mechanism of action of acetaminophen and what does this mean in regards to the 3 main effects of NSAIDs
inhibits PG synthesis centrally; antipyretic and analgesic but no anti-inflammatory effect
