NSAIDs Flashcards
Why is managing chronic pain important?
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
Define nociceptive pain.
Pain originating in tissues that are not part of the nervous system
Define neuropathic pain.
Pain originating in tissues that are part of the nervous system
Is chronic pain (e.g. OA) nociceptive or neuropathic?
Will have components of both!
How do NSAIDs work?
Inhibit prostaglandin production from arachidonic acid by inhibiting cyclooxygenase (COX) enzyme
Some also inhibit leukotriene production by inhibiting lipoxygenase enzyme
How does grapiprant work?
Non-cyclooxygenase inhibiting anti-inflammatory drug
Selective agonist of EP4 receptor, a key prostaglandin E2 receptor that predominantly mediates prostaglandin E2-elicited nociception
Where do NSAIDs act?
Most work in the periphery
Some act centrally in the dorsal horn, by inhibiting COX (precise mechanism unknown)
What are the two types of prostaglandins?
Constitutive (housekeeping) e.g. COX-1 isoenzyme
Inducible (induced by inflammation) e.g. COX-2 isoenzyme
What are the benefits of COX-2 selectivity of NSAIDs?
Advantageous in terms of safety
Likely to reduce risk of renal side effects
Why are prostaglandins essential for the GI system?
Maintenance of mucosal blood flow
Bicarbonate and mucous secretion
Epithelialisation
What side effects can NSAIDs have on the GI system?
GI ulceration
Bleeding
What do prostaglandins regulate in the renal system?
Glomerular filtration rate (GFR)
Renin release
Sodium excretion
What side effects can NSAIDs have on the renal system?
Water retention and oedema
Hypertension
May impair GFR in patients with renal disease/hypotension
May cause renal ischaemia in patients with hypotension
What side effects can NSAIDs have on the hepatic system?
Induce liver enzymes in normal dogs - reduced liver function?
Link to hepatopathy?
What side effects can NSAIDs have on the CNS in cats?
Idiosyncratic dullness
Lethargy
How can NSAIDs affect haemostasis?
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
How can we reduce the risk of side effects with chronic NSAID use?
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
When is GI ulceration with NSAID use more likely?
Pre-existing ulceration
Liver disease
Geriatric
What signs should we ask owners to look out for when using NSAIDs?
Vomiting and diarrhoea
Blood in faeces
Dullness
Anorexia
What is the gold standard approach to beginning NSAID therapy?
Clinical exam
History
Haematology, biochemistry, urinalysis, BP
When should we have rechecks after starting NSAID therapy?
1-2 weeks
How often should we monitor animals on long-term NSAID therapy?
High risk = avoid NSAIDs
Medium risk (concurrent organ disease) = monthly
Low risk = 3-6 months
Describe NSAID cycling and other treatment options.
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.
