1.4 Rational Use of NSAIDs in Clinical Practice

Question 1

How do NSAIDs work?

Answer 1

inhibit COX1/2

• cyclooxygenase is required to convert arachidonic acid (AA) into thromboxanes, prostaglandins, and prostacyclins
• the therapeutic effects of NSAIDs are attributed to the lack of these eicosanoids

without NSAIDs, these eicosanoids (particularly PGs) are released by damaged tissue

Question 2

What are the indications of NSAIDs?

Answer 2

• control of pain and inflammation in non-allergic disorders
• decrease platelet aggregation (treatment of thromboembolisms)

Question 3

What are the actions of COX-1 vs COX-2

Answer 3

COX-1: produces PGs important for physiological function (GIT muscosal barrier, intra-renal perfusion)

COX-2: released by damaged tissue, inflammation, bacterial lipopolysaccharide, ect. - PGE2 is the dominant eicosanoid produced

• inhibition of COX-2 is how clinical benefits are observed (e.g., anti-pyretic/inflammatory)

Question 4

How are NSAIDs classified?

Answer 4

(1) non-selective / non specific

• aspirin
• phenylbutazone
• ketoprofen

(2) preferential: at least 2X greater COX-2 vs COX-1 (usually 4X)

• most therapeutic doses do not inhibit COX-1 meaningfully, but some do
• meloxicam
• carprofen
• mavacoxib, cimicoxib, deracoxib

(3) selective: true COX-2 specific inhibitor (>100X)

• firocoxib (previcox)
• robenocoxib (onsior)

Question 5

What are the species differences for NSAIDs in the dog, cat, and horse?

Answer 5

• Paracetamol: ok in dogs, TOXIC to cats
• carprofen and aspirin have a significantly longer half life in the cat c.f. the dog
• carprofen in non-selective in the horse

Question 6

How do NSAIDs absorb into the body?

Answer 6

well absorbed from the GIT (PO), after IM/SC injection, and topical administration; some drugs can be effective via oromucosal route

Question 7

How do NSAIDs distribute within the body?

Answer 7

• weak acids: penetrate inflammed tissue
• highly protein bound: accumulates in protein-rich exudate

due to this, the duration of effect of NSAIDs may exceed their labeled systemic half-life

Question 8

How are NSAIDs metabolized and eliminated?

Answer 8

main route of elimination is hepatic

• half-life varies considerably between drug and species

in the dog, GI mucosal contact time is greater, allowing for increased risk of adverse effects

Question 9

List the potential adverse effects of NSAIDs

Answer 9

• GIT mucosal damage
• decreased renal perfusion if the animal is hypovolemic, hypernatremic, or has a known/suspected renal insufficiency
• thromboxane inhibition: bleed risk
• avoid in animals with hepatic disease due to liver metabolism

Question 10

What drugs should NSAIDs be use cautiously with?

Answer 10

• ACEi
• a-2 agonists
• diuretics