NSAIDs

Question 1

What are NSAIDs?

Answer 1

Non-steroidal anti-inflammatory drugs

Question 2

Give examples of commonly used small animal NSAIDs

Answer 2

Meloxicam,
Carprofen,
Robenacoxib,
Firocoxib
Cimicoxib
Mavacoxib

Grapiprant

Question 3

Give examples of commonly used equine NSAIDs

Answer 3

Phenylbutazone (suxibuzone)
Flunixin meglumine
Meloxicam

Question 4

Give examples of commonly used farm animal NSAIDs

Answer 4

Meloxicam,
Ketoprofen,
Carprofen

Question 5

How does injury cause pain?

Answer 5

Injury => disruption to cell membrane - phospholipids metabolised (by phospholipase A2) => arachidonic acid => COX-1 or COX-2 => prostaglandins => pain and oedema

Question 6

What are the effects of NSAIDs?

Answer 6

Anti-inflammatory effect
Analgesic effect
Anti-pyretic effect

Question 7

Describe the common anti-inflammatory action of NSAIDs

Answer 7

the decrease in PGE2 and PGI (prostaglandins) reduces vasodilation and, indirectly oedema

Question 8

Describe the common analgesic effect of NSAIDs

Answer 8

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

Question 9

Describe the common anti-pyretic effect of NSAIDs

Answer 9

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

Question 10

What is the common mode of action of NSAIDs?

Answer 10

Inhibit COX enzymes and thus prostanoid synthesis in inflammatory cells. Inhibition of COX2 isoform is crucial for their therapeutic action

Question 11

What are the general pharmacokinetic properties of NSAIDs?

Answer 11

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

Question 12

What are the different classes of NSAIDs?

Answer 12

Salicylates
Phenylbutazone
Ketoprofen
Carprofen
Flunixin
Oxicam derivative
Coxib

Question 13

Describe the features of salicylates

Answer 13

Non-selective
Irreversible interaction with COX
Mild to moderate pain
Aspirin

Question 14

Describe the features of Phenylbutazone

Answer 14

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

Question 15

Describe the features of Ketoprofen

Answer 15

Non-selective
Acute pain and chronic pain from osteoarthritis
Alleviation of inflammation and pain associated with MSK and GI disorders;

Question 16

Describe the features of carprofen

Answer 16

COX2 preferential
Post-operative pain and inflammation
Reduction of chronic inflammation
Adjunct to reduce pain associated with acute infectious respiratory disease and mastitis.

Question 17

Describe the features of flunixin

Answer 17

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

Question 18

Describe the features of oxicam derivatives

Answer 18

COX2 selective
Alleviation of inflammation and pain in chronic MSK disorders and post-operative pain
Meloxicam,
Piroxicam

Question 19

Describe the features of coxib drugs

Answer 19

Highly COX2 selective ie >100 fold selectivity for COX2 over COX1
Pain and inflammation associated with osteoarthritis and peri-operative
Robenacoxib
Firocoxib
Mavacoxib
Cimicoxib

Question 20

What are the contraindications of using NSAIDs?

Answer 20

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.

Question 21

What are the common unwanted effects of NSAIDs?

Answer 21

GI disturbances
Adverse cardiovascular effects
Reversible renal insufficiency
Bronchospasm

Question 22

What is the cause of GI disturbances due to NSAIDs?

Answer 22

Gastric and intestinal damage (ulceration and bleeding) may occur with chronic use. This due to the suppression of gastroprotective PGs in gastric mucosa

Question 23

What is the cause of Adverse cardiovascular effects due to NSAIDs?

Answer 23

may be related to COX2 inhibition in the kidney and elsewhere leading to hypertension

Question 24

What is the cause of reversible renal insufficiency due to NSAIDs?

Answer 24

Mainly seen in patients with compromised renal function when the compensatory PGI2/PGE2-mediated vasodilation is inhibited

Question 25

Describe the action of grapiprant

Answer 25

Selective antagonist of the EP4 receptor (receptor that mediates PGE2-induced nociception).

Question 26

Describe the pharmacokinetics of grapiprant?

Answer 26

Rapid absorption (~1h) after oral treatment – decreased by food
Grapiprant is primarily excreted via faeces (largely unchanged) but also directly renal excreted

Question 27

What are the contraindications of grapiprant?

Answer 27

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