NSAIDs Flashcards
What are NSAIDs?
Non-steroidal anti-inflammatory drugs
Give examples of commonly used small animal NSAIDs
Meloxicam,
Carprofen,
Robenacoxib,
Firocoxib
Cimicoxib
Mavacoxib
Grapiprant
Give examples of commonly used equine NSAIDs
Phenylbutazone (suxibuzone)
Flunixin meglumine
Meloxicam
Give examples of commonly used farm animal NSAIDs
Meloxicam,
Ketoprofen,
Carprofen
How does injury cause pain?
Injury => disruption to cell membrane - phospholipids metabolised (by phospholipase A2) => arachidonic acid => COX-1 or COX-2 => prostaglandins => pain and oedema
What are the effects of NSAIDs?
Anti-inflammatory effect
Analgesic effect
Anti-pyretic effect
Describe the common anti-inflammatory action of NSAIDs
the decrease in PGE2 and PGI (prostaglandins) reduces vasodilation and, indirectly oedema
Describe the common analgesic effect of NSAIDs
decreased PG generation means reduced sensation of nociceptive nerve ending to inflammatory mediators such as bradykinin.
Relief of headache is probably due to decreased PG-mediated vasodilation
Describe the common anti-pyretic effect of NSAIDs
Interleukin 1 releases PG in the CNS, where they elevate the hypothalamic set point for temperature control, thus causing fever. NSAIDs prevent this.
What is the common mode of action of NSAIDs?
Inhibit COX enzymes and thus prostanoid synthesis in inflammatory cells. Inhibition of COX2 isoform is crucial for their therapeutic action
What are the general pharmacokinetic properties of NSAIDs?
Well absorbed after oral administration (food can impair absorption of some)
Some can be given IV, IM or SC administration (quicker onset, load dose)
High plasma protein binding
Bio-transformed in liver to inactive metabolites but limited direct excretion via kidney
What are the different classes of NSAIDs?
Salicylates
Phenylbutazone
Ketoprofen
Carprofen
Flunixin
Oxicam derivative
Coxib
Describe the features of salicylates
Non-selective
Irreversible interaction with COX
Mild to moderate pain
Aspirin
Describe the features of Phenylbutazone
Non-selective
Management of mild-moderate pain & inflammation
Main metabolite has similar properties
Low therapeutic index
Half-life: 3-6h
Do not use in cats
Describe the features of Ketoprofen
Non-selective
Acute pain and chronic pain from osteoarthritis
Alleviation of inflammation and pain associated with MSK and GI disorders;
Describe the features of carprofen
COX2 preferential
Post-operative pain and inflammation
Reduction of chronic inflammation
Adjunct to reduce pain associated with acute infectious respiratory disease and mastitis.
Describe the features of flunixin
Alleviation of inflammation and pain associated with MSK, respiratory and GI disorders.
Describe the features of oxicam derivatives
COX2 selective
Alleviation of inflammation and pain in chronic MSK disorders and post-operative pain
Meloxicam,
Piroxicam
Describe the features of coxib drugs
Highly COX2 selective ie >100 fold selectivity for COX2 over COX1
Pain and inflammation associated with osteoarthritis and peri-operative
Robenacoxib
Firocoxib
Mavacoxib
Cimicoxib
What are the contraindications of using NSAIDs?
Do not administer with different NSAIDs concurrently or within 24 hours of each other ie need a period of time when changing NSAIDs
Do not use in animals suffering from cardiac, hepatic or renal disease; where there is the possibility of gastrointestinal ulceration or bleeding.
Concurrent administration of potentially nephrotoxic drugs should be avoided.
What are the common unwanted effects of NSAIDs?
GI disturbances
Adverse cardiovascular effects
Reversible renal insufficiency
Bronchospasm
What is the cause of GI disturbances due to NSAIDs?
Gastric and intestinal damage (ulceration and bleeding) may occur with chronic use. This due to the suppression of gastroprotective PGs in gastric mucosa
What is the cause of Adverse cardiovascular effects due to NSAIDs?
may be related to COX2 inhibition in the kidney and elsewhere leading to hypertension
What is the cause of reversible renal insufficiency due to NSAIDs?
Mainly seen in patients with compromised renal function when the compensatory PGI2/PGE2-mediated vasodilation is inhibited
Describe the action of grapiprant
Selective antagonist of the EP4 receptor (receptor that mediates PGE2-induced nociception).
Describe the pharmacokinetics of grapiprant?
Rapid absorption (~1h) after oral treatment – decreased by food
Grapiprant is primarily excreted via faeces (largely unchanged) but also directly renal excreted
What are the contraindications of grapiprant?
Use with caution in dogs suffering from pre-existing liver, cardiovascular, renal or GI disease.
