NSAIDs

Question 1

Why is managing chronic pain important?

Answer 1

Chronic pain is maladaptive and of no benefit
Pain is a welfare issue
Feeling of pain compromises sensory discriminative aspect being processed by the brain and then interpreted with both physical and emotional components

Question 2

Define nociceptive pain.

Answer 2

Pain originating in tissues that are not part of the nervous system

Question 3

Define neuropathic pain.

Answer 3

Pain originating in tissues that are part of the nervous system

Question 4

Is chronic pain (e.g. OA) nociceptive or neuropathic?

Answer 4

Will have components of both!

Question 5

How do NSAIDs work?

Answer 5

Inhibit prostaglandin production from arachidonic acid by inhibiting cyclooxygenase (COX) enzyme

Some also inhibit leukotriene production by inhibiting lipoxygenase enzyme

Question 6

How does grapiprant work?

Answer 6

Non-cyclooxygenase inhibiting anti-inflammatory drug

Selective agonist of EP4 receptor, a key prostaglandin E2 receptor that predominantly mediates prostaglandin E2-elicited nociception

Question 7

Where do NSAIDs act?

Answer 7

Most work in the periphery

Some act centrally in the dorsal horn, by inhibiting COX (precise mechanism unknown)

Question 8

What are the two types of prostaglandins?

Answer 8

Constitutive (housekeeping) e.g. COX-1 isoenzyme
Inducible (induced by inflammation) e.g. COX-2 isoenzyme

Question 9

What are the benefits of COX-2 selectivity of NSAIDs?

Answer 9

Advantageous in terms of safety
Likely to reduce risk of renal side effects

Question 10

Why are prostaglandins essential for the GI system?

Answer 10

Maintenance of mucosal blood flow
Bicarbonate and mucous secretion
Epithelialisation

Question 11

What side effects can NSAIDs have on the GI system?

Answer 11

GI ulceration
Bleeding

Question 12

What do prostaglandins regulate in the renal system?

Answer 12

Glomerular filtration rate (GFR)
Renin release
Sodium excretion

Question 13

What side effects can NSAIDs have on the renal system?

Answer 13

Water retention and oedema
Hypertension
May impair GFR in patients with renal disease/hypotension
May cause renal ischaemia in patients with hypotension

Question 14

What side effects can NSAIDs have on the hepatic system?

Answer 14

Induce liver enzymes in normal dogs - reduced liver function?
Link to hepatopathy?

Question 15

What side effects can NSAIDs have on the CNS in cats?

Answer 15

Idiosyncratic dullness
Lethargy

Question 16

How can NSAIDs affect haemostasis?

Answer 16

Unspecific for COX = can affect clotting
Prolong markers for blood clotting if given for long courses (30-90 days) but not linked to clinical signs of bleeding

Question 17

How can we reduce the risk of side effects with chronic NSAID use?

Answer 17

Do not exceed licensed dose
Do not give two NSAIDs concurrently
Do not give NSAIDs and corticosteroids concurrently
Do not give NSAIDs to dehydrated/hypotensive patients
Warn owners of risks

Question 18

When is GI ulceration with NSAID use more likely?

Answer 18

Pre-existing ulceration
Liver disease
Geriatric

Question 19

What signs should we ask owners to look out for when using NSAIDs?

Answer 19

Vomiting and diarrhoea
Blood in faeces
Dullness
Anorexia

Question 20

What is the gold standard approach to beginning NSAID therapy?

Answer 20

Clinical exam
History
Haematology, biochemistry, urinalysis, BP

Question 21

When should we have rechecks after starting NSAID therapy?

Answer 21

1-2 weeks

Question 22

How often should we monitor animals on long-term NSAID therapy?

Answer 22

High risk = avoid NSAIDs
Medium risk (concurrent organ disease) = monthly
Low risk = 3-6 months

Question 23

Describe NSAID cycling and other treatment options.

Answer 23

If one NSAID not tolerated (due to side effects) or not adequately efficacious, can swap to another in dogs
Introduce (non-licensed) analgesic adjunctive therapies e.g. gabapentin
Diet, weight management, physiotherapy etc.