NSAIDs

Question 1

What does NSAID stand for?

Answer 1

Non-steroidal Anti-Inflammatory Drug

Question 2

What are commonly used small animal NSAIDs?

Answer 2

Meloxicam
Carprofen
Robenacoxib
Firocoxib
Grapiprant

Question 3

What are commonly used equine NSAIDs?

Answer 3

Phenylbutazone (suxibuzone)
Flunixin meglumine
Meloxicam

Question 4

What are commonly used Farm Animal NSAIDs?

Answer 4

Meloxicam
Ketoprofen

Question 5

What occurs in normal injury?

Answer 5

Release of phospholipids which are broken down into arachidonic acid
COX 1 or COX2 enzymes act on arachidonic acid
Leads to production of prostaglandins and thromboxane

Question 6

How do NSAIDs work? (Pharmacodynamics)

Answer 6

Inhibit action of COX enzymes
Therefore inhibit prostaglandin synthesis

Question 7

Which isoform is more important in NSAIDs?

Answer 7

COX2 - unregulated during injury

Question 8

What effects do COX2 selection have?

Answer 8

Anti-inflammatory effect
Analgesic effect
Anti-pyretic effect

Question 9

How does selection for COX2 have an anti-inflammatory effect?

Answer 9

The decrease in PGE2 and PGI reduces vasodilation
Indirectly reduces oedema

Question 10

How does selection for COX2 have an analgesic effect?

Answer 10

Decreased PG generation means reduced sensitisation of nociceptive nerve ending to inflammatory mediators such as bradykinin
Relief of headache is probably due to decreased PG-mediated vasodilation

Question 11

How does selection for COX2 have antipyretic effect?

Answer 11

Interleukin 1 releases PG in the CNS, where they elevate the hypothalamic set point for temperature control, thus causing fever
NSAIDs prevent this

Question 12

General pharmacokinetic properties of NSAIDs

Answer 12

Weak acids
Well absorbed after oral administration
formulations for IV, IM and SC
Very high plasma protein binding
Most bio-transformed in the liver to inactive metabolites

There is variation in elimination half-life between NSAIDS and species

Question 13

Types of NSAIDs

Answer 13

Salicylates
Phenylbutazone
Carprofen
Ketoprofen
Flunixin
Oxicam derivatives
Coxib

Question 14

Salicylate action

Answer 14

Non-selective
Methyl group causes irreversible interaction with COS

Question 15

Salicylate usage

Answer 15

Mild to moderate pain

Question 16

Salicylate example/licensing

Answer 16

Aspirin
None licensed in veterinary medicine

Question 17

Phenylbutazone action

Answer 17

Non-selective
Main metabolite also has similar properties
Low therapeutic index

Question 18

Phenylbutazone usage

Answer 18

Mild to moderate pain and inflammation
DO NOT USE IN CATS

Question 19

Phenylbutazone licensing

Answer 19

Horses

Question 20

Carprofen action

Answer 20

COX2 preferential but not selective

Question 21

Carprofen usage

Answer 21

Post-operative pain and inflammation
Reduction of chronic inflammation
Adjunct to reduce pain with acute infectious respiratory disease and mastitis

Question 22

Carprofen licensing

Answer 22

Dogs
Cats

Question 23

Ketoprofen action and usage

Answer 23

Non-selective

Question 24

Ketoprofen usage

Answer 24

Acute pain and chronic pain from osteoarthritis
Alleviation of inflammation and pain associated with MSK and GI disorders

Question 25

Ketoprofen licensing

Answer 25

Cattle Horses Pigs Not licenced for peri-operative indication

Question 26

Flunixin usage

Answer 26

Alleviation of inflammation and pain associated with MSK, respiratory and GI disorders

Question 27

Flunixin Licensing

Answer 27

Cattle Horses Pigs

Question 28

Oxicam derivatives action

Answer 28

COX2 selective

Question 29

Oxicam derivatives usage

Answer 29

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

Question 30

Oxicam derivatives example and licensing

Answer 30

Meloxicam - Small animal, Farm Animal, Horses

Question 31

Coxib action

Answer 31

Highly COX2 selective >100 fold selectivity for COX2 over COX1

Question 32

Coxib uses

Answer 32

Pain and inflammation associated with osteoarthritis and peri-operative

Question 33

Coxib examples

Answer 33

Robenacoxib Firocoxib Mavacoxib Cimicoxib

Question 34

Coxib licensing

Answer 34

Robenacoxib - Small animal Firocoxib - Small animal, horses Mavacoxib - dogs Cimicoxib - dogs

Question 35

Grapiprant Action

Answer 35

NOT COX INHIBITOR - still affects prostaglandin * Selective antagonist of the EP4 receptor ○ Receptor that mediates PGE2-induced nociception Rapid absorption after oral treatment

Question 36

Grapiprant licensing

Answer 36

small animals

Question 37

Grapiprant cautions

Answer 37

Dogs suffering from pre-existing liver, cardiovascular or GI disease

Question 38

Why are there contraindications to COX inhibitors

Answer 38

Unwanted side effects come from inhibition of COX1 Usually in older patients

Question 39

What are the contraindications of COX inhibitors?

Answer 39

GI disturbances: ○ Due to reduction in protective prostaglandins in gastric mucosa ○ Gastric and intestinal damage may occur with chronic use with risk of ulceration and bleeding Adverse cardiovascular effects: ○ Can occur with many NSAIDs including coxib ○ May be related to COX2 inhibition in the kidney 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 40

How long should you wait between administering different NSAIDs

Answer 40

24 hours Do not administer different NSAIDs concurrently

Question 41

When should you not use NSAIDs?

Answer 41

Animals suffering from cardiac, hepatic or renal disease Where there is the possibility of gastrointestinal ulceration or bleeding