Chapter 76 - NSAIDs

Question 1

Are COX-1–induced prostaglandins constitutive or induced ?

And COX-2?

Answer 1

COX-1: BOTH - most are constitutive, but some are also produced in response to tissue injury.
COX-2: BOTH - many are inducible, but constitutive COX-2 prostaglandins found in the brain, intestine, and kidneys in many species

Question 2

Which are COX-2 selective, which are dual-acting (COX 1 and 2), which are COX-3 selective?

• Aspirin
• Carprofen
• Meloxicam
• Firocoxib
• Acetaminophen

Answer 2

• Aspirin : dual-acting
• Carprofen: COX-2 selective
• Meloxicam: COX-2 selective
• Firocoxib: COX-2 selective
• Acetaminophen: COX-3 selective (COX-3 has been isolated in dog’s brain, inflammatory and pyretic effects)

Question 3

What are the digestive protective effects of COX-induced PG ?

Answer 3

• COX-1 induced PG increase gastric mucous production and local blood flow,
• COX-2 is stimulated when there is intestinal mucosal damage - produces PG important for mucosal healing
• 1 and 2 - induced PG regulate GI motility

Question 4

Which is the NSAID that has the least GI side effects when used long term in dogs:

• meloxicam
• ketoprofen
• carprofen
• flunixin meglumine
• etodolac

Answer 4

Carprofen

Question 5

What is the solubility of NSAIDs in stomach acidity? What is the consequence?

Answer 5

• Lipid soluble (weak acids)
• Penetrate easily into gastric cells, where they become trapped in the relatively more alkaline environment.
  => high local concentration of NSAIDs in the gastric mucosa
  => might be why adverse effects in gastrointestinal system at lower doses than in other organ systems

Question 6

How do you treat a non-symptomatic NSAIDs toxicity? Treatment duration? What is an early sign of renal toxicity to monitor?

Answer 6

• Induction of emesis if within 2 to 4 hours of ingestion.
• Activated charcoal: many NSAIDs undergo enterohepatic recycling => repeated dosing every 4 to 6 hours
• Intravenous fluid therapy: vital to maintain intestinal and renal perfusion
• Gastrointestinal protectants: prevent or treat gastric mucosal injury
• Treatment duration: until at least three halflives have passed - however, NSAIDs can have a longer half-life in the tissues than in the plasma, so treatment should continue if there is laboratory or clinical abnormalities
• Urine sediment: monitor daily (even in asymptomatic animals), to look for evidence of renal casts (tubular injury)

Question 7

A dog is presented to you for having stolen NSAIDS from their owner. The owner was not home and the ingestion happened between 2 and 8 hours from now. The patient vomited 3 times and had diarrhea on the sofa, motivating the owner to come to the ER.
Do you induce vomiting ? Do you give activated charcoal?

Answer 7

No. If patients are showing clinical signs of NSAID toxicity, then decontamination procedures such as emesis or activated charcoal are not beneficial because the medication will already have been absorbed.

Question 8

By which mechanism can NSAIDs cause kidney damage when administered to an hypovolemic paient?

Answer 8

• Prostaglandin-mediated effect of local vasodilation is diminished or lost
• COX-2–selective medications can increase the relative production of thromboxanes, which have local vasoconstrictive effects