NSAIDs

Question 1

What are some commonly used NSAIDs in small animals

Answer 1

Meloxicam,
Carprofen,
Robenacoxib,
Firocoxib
Cimicoxib
Mavacoxib
Grapiprant

Question 2

What are commonly used NSAIDs in equine

Answer 2

Phenylbutazone (suxibuzone)
Flunixin meglumine
Meloxicam

Question 3

What are commonly used NSAIDs in farm animals

Answer 3

Meloxicam,
Ketoprofen,
Carprofen

Question 4

How does an injury cause pain?

Answer 4

1. Injury occurs:
   - Disruption of cell membrane
2. Phospholipid metabolism:
   - Phospholipids in disrupted membrane metabolised by phospholipase A₂, releasing arachidonic acid
3. Arachidonic acid pathways:
   - Processed by Cyclo-oxygenase 1 (COX-1) or Cyclo-oxygenase 2 (COX-2) enzymes
4. Prostaglandin production:
   - COX enzymes convert arachidonic acid into prostaglandins, thromboxanes, & other prostanoids.
5. Pain and oedema:
   - Prostaglandins sensitise nociceptive neurons, causing pain
   - Also promote vasodilation & increased vascular permeability, leading to oedema

Question 5

What are the effects of NSAIDs

Answer 5

Anti-inflammatory effect
Analgesic effect
Anti-pyretic effect

Question 6

What do NSAIDs inhibit

Answer 6

Inhibit COX enzymes & thus prostanoid synthesis in inflammatory cells

Inhibition of COX2 isoform is crucial for their therapeutic action

Question 7

Describe the anti-inflammatory action of NSAIDs

Answer 7

Decrease in PGE2 & PGI reduces vasodilation & indirectly oedema

Question 8

Describe the analgesic effect of NSAIDs

Answer 8

Decreased PG generation –> reduced sensation of nociceptive nerve ending to inflammatory mediators (e.g. bradykinin)

Relief of headache probs due to decreased PG-mediated vasodilation

Question 9

Describe the anti-pyretic effect of NSAIDs

Answer 9

interleukin 1 releases PG in CNS where they elevate hypothalamic set point for temperature control thus causing fever

NSAIDs prevent this

Question 10

What is the difference in COX inhibition between older NSAIDs and “coxibs”?

Answer 10

Older NSAIDs (e.g., aspirin, phenylbutazone) are non-selective COX inhibitors

“Coxibs” (e.g., robenacoxib, firocoxib) are highly COX-2 selective, reducing side effects associated with COX-1 inhibition (e.g., gastric damage).

Question 11

what are the pharmokinetic properties of NSAIDs?

Answer 11

Weak acids: Well absorbed orally within 2–3 hours
- food can impair absorption of some

High plasma protein binding: Up to 99%.

Metabolized in the liver: Inactive metabolites excreted in urine or bile (except mavacoxib, excreted unchanged in bile).

Question 12

What are the different classes of NSAIDs

Answer 12

Salicylates
Phenylbutazone
Ketoprofen
Carprofen
Flunixin
Oxicam derivative
Coxib

Question 13

Describe Salicylates

Answer 13

non-selective

irreversible interaction with COX

mild to moderate pain

e.g. aspirin

Question 14

Describe Phenylbutazone

Answer 14

non-selective

management of mild-moderate pain & inflammation

Main metabolite has similar properties

Low therapeutic index

half-life: 3-6h

don’t use in cats

Question 15

Describe Ketoprofen

Answer 15

non-selective

acute pain & chronic pain from osteoarthritis

alleviation of inflammation & pain associated with MSK & GI disorders

not licensed for peri-operative indication

Question 16

Describe Carprofen

Answer 16

COX2 preferential

post-operative pain & inflammation

Reduction of chronic inflammation

Reduce pain associated with acute infectious respiratory disease & mastitis

Question 17

Describe Flunixin

Answer 17

alleviation of inflammation & pain associated with MSK, respiratory & GI disorders

Question 18

Describe Oxicam derivative

Answer 18

CO2 selective

Alleviation of inflammation & pain in chronic MSK disorders & post-operative pain

e.g. Meloxicam & Piroxicam

Question 19

Describe Coxib

Answer 19

highly COX2 selective

pain & inflammation associated with osteoarthritis & peri-operative

e.g. Robenacoxib, Firocoxib, Mavacoxib, Cimicoxib

Question 20

What are the general contraindications of NSAID use

Answer 20

Do not combine different NSAIDs or administer them within 24 hours of each other.

Avoid use in animals with:
- Cardiac, hepatic, or renal disease.
- GI ulceration or bleeding risk.

Avoid concurrent use with nephrotoxic drugs.

Question 21

What are the common side effects of NSAIDs

Answer 21

Gastrointestinal: Ulceration & bleeding (due to suppressed gastroprotective prostaglandins in gastric mucosa)

Cardiovascular: Hypertension and potential heart issues

Renal: Reversible renal insufficiency in compromised animals

Bronchospasm: In aspirin-sensitive animals.

Question 22

What is Grapiprant & how does it differ from traditional NSAIDs

Answer 22

Grapiprant is a selective EP4 receptor antagonist, targeting PGE2-induced nociception without inhibiting COX enzymes

It has reduced risk of GI, renal & cardiovascular side effects compared to COX inhibitors

Rapid absorption

Primarily excreted via faeces but also renal

Use with caution in dogs suffering from pre-existing liver, cardiovascular, renal or GI disease