Rational Use of NSAIDs

Question 1

How do NSAIDs reduce inflammation?

Answer 1

inhibit the production of prostaglandins released by damaged tissue by inhibiting cyclo-oxygenase

Question 2

When are NSAIDs indicated?

Answer 2

• controlling pain and inflammation in NON ALLERGIC disorders e.g. degenerative joint disease
• Peri-operative pain management
• Decreasing platelet aggregation e.g. heartworm disease, thromboembolism

Question 3

What is the name of the pathway that NSAIDs act on and what are the products of these pathways?

Answer 3

Cyclooxygenase pathway
COX-1 (physiologic COX)
COX-2 (the inducible COX)

Question 4

What is the role of COX-1?

Answer 4

Physiologic roles- mucosal protection, renal blood flow & haemostasis

Question 5

What is the role of COX-2?

Answer 5

Inducible behaviours- inflammation, pain & fever

Question 6

How does inhibiting COX-2 helps with tumours?

Answer 6

Tumours produce COX-2 so inhibiting can slow the growth of these tumours

Question 7

What are the three types of NSAIDs?

Answer 7

1. Non selective
2. Preferential (mainly inhibit COX-2 with some COX-1 inhibition)
3. Selective (inhibit COX-2 without inhibiting COX-1)

Question 8

How do Corticosteroids reduce inflammation?

Answer 8

Block the production of Phospholipase from the membrane
Phospholipase is usually used to make arachnoid acid which is needed to make COX-1 / COX-2
Therefore Corticosteroids block both COX-1 and COX-2

Question 9

Why are some NSAIDs more toxic than others?

Answer 9

Their COX-1 : COX-2 ratios differ so have different levels of safety depending on their inhibition of COX-1 (the physiological one)

Question 10

Give two examples of non selective COX inhibitors?

Answer 10

Aspirin
Phenylbutazone
Ketoprofen
Tolfenamic acid

Question 11

What are Preferential COX-2 inhibitors good for but what is the risk?

Answer 11

Good for analgesic and anti-inflammatory activity by blocking COX-2
BUT some COX-1 inhibition is possible at elevated doses

Question 12

Preferential COX-2 inhibitors also includes drugs known as…..
Why?

Answer 12

Coxibs- COX-2 selective in humans but NOT in animals

Question 13

Give two examples of Preferential inhibitors of COX-2?

Answer 13

Meloxicam / Metacam
Carprofen
Mavacoxib
Cimicoxib

Question 14

What is the duration of action like for Mavacoxib?

Answer 14

VERY long!- can be given as an NSAID once a month

Question 15

Give two examples of selective inhibitors of COX-2?

Answer 15

Firocoxib
Robenocoxib

Question 16

How do non NSAID Osteoarthritis drugs work?

Answer 16

Prostaglandin (PGE2)- binds to 4 receptors- the EP4 receptor is responsible for pain and inflammation associated with osteoarthritis- inhibiting this receptor inhibits the pain

Question 17

Give an example of a non NSAID Osteoarthritis drug?

Answer 17

Grapiprant / Galliprant

Question 18

Which two NSAIDs are preferred to administer to dogs and what is their mechanism of action?

Answer 18

Carprofen (the COX-2 preferential)
Firocoxib (COX-2 selective)

Question 19

What is the risk of using Carprofen in cats?

Answer 19

Daily dosing leads to GI disaster!- think holes in the intestine

Question 20

Can we use Firocoxib in Cats?
How does its inhibition differ in cats than dogs?

Answer 20

Technically no- not licensed in cats
Acts as a COX-2 preferential in cats rather than selective

Question 21

Which NSAIDs are preferred in Horses and what is their mechanism of action?

Answer 21

Carprofen (non selective)
Firocoxib (selective)

Question 22

How/ Where are NSAIDs best absorbed?

Answer 22

from stomach & small intestine
well absorbed after subcutaneous or intramuscular injection

Question 23

How do the biological properties of NSAIDs make them effective in targeting inflamed tissue?

Answer 23

Weak acids to readily penetrate inflamed tissue
Highly protein bound so readily accumulate in protein rich inflammatory exudate

Question 24

Which route of elimination do NSAIDs follow?

Answer 24

Hepatic

Question 25

Can we give Paracetamol to companion animals?

Answer 25

Cats- NO Dogs- Yes

Question 26

What are some potential side effects of NSAIDs?

Answer 26

GI damage Renal toxicity Haematological such as blood clotting

Question 27

When there is no pre existing GI injury, are NSAIDs still a risk?

Answer 27

Depends on the NSAID- Non selective ones are higher risk as COX-1 and COX-2 need to be inhibited to generate a mucosal injury in the absence of a pre existing one

Question 28

How do NSAIDs cause GI damage?

Answer 28

Disrupt the mucosal gel layer of the GI tract meaning acid is let in

Question 29

Why do COX-2 selective drugs have higher GI risks in dogs?

Answer 29

Dogs have a higher requirement for COX-2 in the duodenum (both COX have protective roles in the duodenum but COX-2 has a bigger role) so COX-2 inhibitors cause a higher degree of duodenal ulceration compared with non selective NSAIDs

Question 30

What can increase the ulcerogenic potential of an NSAID?

Answer 30

Concurrent corticosteroids Dehydration Hypovolaemic Shock

Question 31

How does COX-2 inhibition effect the kidney?

Answer 31

COX-2 has physiological roles in the kidney so when renal perfusion is reduced, COX-1 and COX-2 maintain renal blood flow through vasodilatory actions hence why you cannot use NSAIDs in a dehydrated animal

Question 32

Can we use Galliprant (the EP4 receptor antagonist) as an alternative to NSAIDs in patients with renal compromise?

Answer 32

NO- EP4 is expressed in the glomerulus and collecting duct & helps regulate glomerular tone and renin release

Question 33

Why do NSAIDs carry the risk of Haematopoietic side effects?

Answer 33

COX-1 inhibitors also inhibit Thromboxane which is a vasoconstrictor and activates platelet aggregation- inhibition of this can lead to increased bleeding

Question 34

Due to the risk of Nephrotoxicity with NSAIDs in patients with pre exisiting renal issues, can we use ACE inhibitors to reduce inflammation instead?

Answer 34

NO- ACE inhibitors decrease renal vascular resistance, therefore increasing blood flow which strains the renal system

Question 35

What effect does alpha2 agonists have on NSAIDs?

Answer 35

Using alpha2 agonists as premedication before administering an NSAID may enhance the analgesic and anti-inflammatory effect of NSAIDs but also improve gatstrointestinal tolerability

Question 36

Why should you avoid a high dose of Acepromazine as a pre medication before administering an NSAID?

Answer 36

Acepromazine interacts with NSAIDs- causes an increased risk of Hypertension

Question 37

What is the result of using Diuretics and NSAIDs at the same time?

Answer 37

COX-2 inhibition reduces the effect of the diuretic