NSAIDs

What does NSAIDs stand for?

non-steroidal anti-inflammatory drugs

What are NSAIDs?

non-narcotics that provide analgesic, anti-inflammatory, and anti-pyretic (fever)

What are the classifications of NSAIDs?

based on specific enzyme and eicosanoid metabolites used

What are the common uses of NSAIDs?

pain and inflammation from osteoarthritis, surgery and trauma

What are the advantages of the NSAIDs? Why would you use these over other narcotic analgesics?

more rapid recovery after anesthesia, no sedation, combination possibility

When would you combine NSAIDs with other analgesics? Usually combined with what?

where greater analgesia is required, combine with opioids to synergize

What does combination dosing do to the dose of the narcotic agent?

requires smaller dose because of synergizing

What is hyperalgesia?

pain response to stimuli that do not normally induce pain, in other words, lowers the pain threshold

What typical stimuli cause hyperalgesia?

prostaglandins and leukotrienes

What is the function of prostaglandins in pain and inflammation?

magnify nociceptive transmission to the spinal cord and act as mediators of inflammation

COX-1 is ________ expressed in a large number of tissue.

constitutively

What is COX-1 activity?

mostly physiologic activity; protection of the gastric mucosa, maintenance of renal blood flow, vascular homeostasis (prostacyclin production)

COX-2 is considered the _______ enzyme.

inducible

What increases expression of COX-2?

in response to serum growth factors, cytokines (inflammation) and mitogens

In what animals is COX-2 constitutively expressed? Where?

brain, kidney, and vascular smooth muscle of rodents

What is COX-2 activity?

both physiologic like COX-1 as well as pathologic such as pain, inflammation, fever

What’s different about the COX-1 and COX-2 inhibitors?

binding pocket in COX-2 enzyme is wider so selective COX-2 inhibitors are structurally larger than nonselective that are more narrow (smaller)

What is the exception of COX-1/2 inhibitors blocking the binding pocket?

aspirin acetylates the binding pocket causes irreversible inhibition

What is COX selectivity?

ratio of inhibition of COX-1 compared to COX-2 for a given NSAID

Which of the following lists approved veterinary NSAIDs in order of increasing selectivity for COX-2?

phenylbutazone, flunixin meglumine, meloxicam, carprofen, deracoxib, firocoxib

NSAIDS are hypothesized to be _____ efficacious against inflammation in comparison to glucocorticosteroids.

less

At what percentage does peak analgesia occur with COX-2 inhibition?

80%

At what percentage do GI effects occur with COX-1 inhibition?

10-20%

What does the safety profile depend on for species/breed variations?

enzyme specificity, pharmacokinetics, metabolism

Which phase 2 conjugation method is the major route of elimination/metabolization of NSAIDs?

glucuronidation

Why is the use of NSAIDs like aspirin and acetaminophen harmful to cats?

they are deficient in the liver enzyme glucuronyl transferase

What are the recommendations of NSAIDs that can be safely used in cats?

ketoprofen in canada and UK, meloxicam (only one dose), robenacoxib (up to 3 doses)

What can NSAID-induced gastric ulceration be precipitated by?

co-administration of corticosteroids, dehydration, hypovolemic shock, disruption of normal blood flow in gut

True or False: NSAIDs should never be administered in combination with glucocorticoids or other NSAIDs.

True

NSAIDs are heavily protein bound, what can this cause?

can displace oral anticoagulants and other heavily protein bound drugs from protein binding sites (usually balanced by metabolism and excretion of unbound drug)

What are the possible side effects of NSAIDs?

renal toxicity and hepatic toxicity

How can NSAIDs cause renal toxicity?

reduced renal blood flow due to prostaglandin inhibition leads to reduced filtration, toxicity can be severe if the animal is volume or sodium depleted

How can NSAIDs cause hepatic toxicity?

uncommon in dogs but labradors can have idiosyncratic drug reactions when receiving carprofen; horses taking phenylbutazone

What is carprofen?

COX-2 selective inhibitor will effects that may be due to PLA₂ inhibition also

What is carprofen used for?

acute and chronic pain, osteoarthritis, perioperative analgesia (comparable to opiods in dogs and cats, may be longer acting than some drugs)

What is the common dosing of carprofen?

every 12 to 24 hours in dogs but just a single dose in cats

What is special about carprofen? Think side effects.

labs may exhibit idiosyncratic hepatotoxicity; extended half-life in cats makes chronic administration problematic

What is meloxicam?

preferential COX-2 inhibitor

What is meloxicam used for?

soft tissue or musculoskeletal pain including osteoarthritis in dogs, perioperative pain for orthopedic or soft tissue surgeries

What is the common dosing of meloxicam?

once daily for dogs and short term (1 day) treatment for cats

What is firocoxib?

highly selective for COX-2 that was developed specifically for animals

What is firocoxib used for?

pain and inflammation associated with osteoarthritis and treatment of transitional cell carcinoma (although not officially approved for this use)

What is the common dosing for firocoxib?

once daily dosing (not cats)

What is robenacoxib?

preferential COX-2 inhibitor, appears to be relatively selective for COX-2 in dogs and cats

What is robenacoxib used for?

post-operative pain associated with orthopedic surgery, ovariohysterectomy and castration

What is the common dosing for robenacoxib?

approved in cats up to 3 doses

What is unique about robenacoxib?

half-life is 1.5-3 hours in cats so it targets inflammation but does not circulate for an extended period

What is grapiprant?

inhibits EP4 receptor (PGE2 receptor)

What is grapiprant used for?

inhibits inflammation

What is unique about grapiprant?

indicated for dogs with renal dysfunction allowing it to be used long-terms in dogs with osteoarthritis

What is librela?

monoclonal antibody against NGF (nerve growth factor)

What are the common NSAIDs used in dogs?

meloxicam, carprofen, firocoxib, grapiprant

What are the common NSAIDs used in cats?

robenacoxib, meloxicam

What are the common NSAIDs used in equine?

phenylbutazone, firocoxib, flunixin meglumate