NSAIDS

Question 1

list commonly used NSAIDs in small animals

Answer 1

• Meloxicam,
• Carprofen,
• Robenacoxib,
• Firocoxib
• Cimicoxib
• Mavacoxib
• Grapiprant

Question 2

list commonly used NSAIDs in horses

Answer 2

• Phenylbutazone (suxibuzone)
• Flunixin meglumine
• Meloxicam

Question 3

list commonly used NSAIDs in farm animals

Answer 3

• Meloxicam,
• Ketoprofen,
• Carprofen

Question 4

give an overview of how NSAIDs work

Answer 4

• inhibit COX enzymes and thus prostanoid sythesis in inflammatory cells. inhibition of COX2 isoform is crucial for their therapeutic action
• the decrease in PGE2 and PGI reduces vasodilation and indirectly oedema, thus anti-inflammatory action
• 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, thus analgesic effect
• Interleukin 1 releases PG in the CNS, where they elevate the hypothalamic set point for temperature control, thus causing fever. NSAIDs prevent this, thus anti-pyretic effect

Question 5

what are the general properties of the parhamcokinetics of NSAIDs

Answer 5

• Weak acids that are generally well absorbed after PO administration (typically within 2-3h). However, food can impair absorption of some (phenylbutazone, flunixin, robenacoxib)
• Several NSAIDs have formulations for IV, IM and SC administration
• Very high plasma protein binding (up to 99%). Potential for drug displacement but limited clinical effects on free drug concentrations. As inflammation leads to extravasation of protein, NSAIDs tend to concentrate in these areas
• Bio-transformed in the liver to inactive metabolites, some but limited direct excretion via kidney. Exception is mavacoxib, which is not metabolised and is excreted via bile.

Question 6

list the different classes of NSAIDs

Answer 6

• Salicylates
• phenylbutazone
• ketoprofen
• carprofen
• flunixin
• oxicam derivative
• coxib

Question 7

which animals should not receive NSAIDs

Answer 7

animals suffering from cardiac, hepatic or renal disease or where there is the possibility of GI ulceration or bleeding

Question 8

what are salicylates

Answer 8

Question 9

what are phenybutazones

Answer 9

Question 10

what are ketoprofens

Answer 10

Question 11

what are carprofens

Answer 11

Question 12

what are flunixins

Answer 12

Question 13

what are oxicam derivatives

Answer 13

Question 14

what are coxibs

Answer 14

Question 15

list some general unwanted effects of COX inhibitors

Answer 15

Unwanted effects, many stemming from inhibition of the constitutive housekeeping COX1 isoform are common, particularly in older patients and include:
* GI disturbances: Gastric and intestinal damage (ulceration and bleeding) may occur with chronic use. This due to the suppression of gastroprotective PGs in gastric mucosa
* Adverse cardiovascular effects: these can occur with many NSAIDs including coxib and may be related to COX2 inhibition in the kidney and elsewhere leading to hypertension
* Reversible renal insufficiency: Mainly seen in patients with compromised renal function when the compensatory PGI2/PGE2-mediated vasodilation is inhibited
* Bronchospasm: Seen in aspirin-sensitive asthmatics

Question 16

what is grapiprant

Answer 16

• Selective antagonist of the EP4 receptor (receptor that mediates PGE2-induced nociception).
• Rapid absorption (~1h) after oral treatment – decreased by food
• Grapiprant is primarily excreted via faeces (largely unchanged) but also directly renal excreted
• Use with caution in dogs suffering from pre-existing liver, cardiovascular, renal or GI disease.

Question 17

What enzyme do corticosteroids inhibit in the inflammatory cascade?

Answer 17

Phospholipase A2, preventing the release of arachidonic acid from cell membrane phospholipids.

Question 18

What is the role of phospholipase A2 in inflammation?

Answer 18

It releases arachidonic acid from cell membranes, a precursor to prostaglandins and leukotrienes.

Question 19

What enzyme converts arachidonic acid to prostaglandins and thromboxanes?

Answer 19

Cyclooxygenase (COX-1 and COX-2) enzymes.

Question 20

What is the role of COX-1?

Answer 20

Constitutively expressed enzyme involved in gastric protection, platelet aggregation, and renal perfusion.

Question 21

What is the role of COX-2?

Answer 21

Inducible enzyme involved in inflammation, pain, and fever.

Question 22

Which NSAIDs are non-selective COX inhibitors?

Answer 22

Phenylbutazone and Flunixin – inhibit both COX-1 and COX-2.

Question 23

Which NSAIDs are selective or preferential COX-2 inhibitors?

Answer 23

Meloxicam, Robenacoxib, and Mavacoxib.

Question 24

What are the risks of using non-selective NSAIDs?

Answer 24

Gastrointestinal ulceration, renal damage, and impaired platelet function due to COX-1 inhibition.

Question 25

What does Grapiprant (Galliprant) target?

Answer 25

The EP4 receptor, which mediates PGE2-induced pain and inflammation. It does not inhibit COX enzymes.

Question 26

What is the advantage of Galliprant over traditional NSAIDs?

Answer 26

Provides pain relief without blocking protective prostaglandins—less risk of GI/renal side effects.

Question 27

Which NSAID is long-acting and excreted via bile rather than the kidney?

Answer 27

Mavacoxib – not metabolized and has a prolonged half-life.

Question 28

What NSAIDs should you avoid in animals with renal, hepatic, or cardiac disease?

Answer 28

All traditional NSAIDs including phenylbutazone, flunixin, meloxicam, robenacoxib, and mavacoxib.

Question 29

Why is food a concern with some NSAID absorption?

Answer 29

Food can impair absorption of phenylbutazone, flunixin, and robenacoxib when given orally.

Question 30

What precautions should be taken when switching NSAIDs?

Answer 30

Allow a washout period of at least 24 hours between different NSAIDs.

Question 31

Give a clinical scenario where Galliprant would be preferred.

Answer 31

A dog with osteoarthritis and a history of GI sensitivity or kidney compromise.

Question 32

Give a clinical scenario for using Meloxicam.

Answer 32

Post-operative pain in dogs or cats, or mild-to-moderate chronic inflammation.

Question 33

What effect do NSAIDs have on protein binding?

Answer 33

Highly protein-bound (up to 99%), potential for drug displacement but limited clinical impact.

Question 34

What happens to NSAIDs during inflammation?

Answer 34

They concentrate in inflamed tissues due to extravasation of plasma proteins.

Question 35

Which pathway produces leukotrienes and is not targeted by NSAIDs?

Answer 35

Lipoxygenase pathway – leads to bronchoconstriction and inflammation.

Question 36

What prostaglandin primarily mediates pain and inflammation via EP4 receptors?

Answer 36

PGE2.

Question 37

make a flow chart of the site of action of the NSAIDs

Answer 37