NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)

NSAIDs

• NSAIDs block the formation of prostaglandins

• NSAIDs are not as effective as steroids at reducing inflammation

• NSAIDs have fewer side effects when compared to steroids

• Also have analgesic and antipyretic properties

Mechanism of Action

• Inhibits prostaglandin and thromboxane synthesis

• Many different types of prostaglandins

• PGE2 is released during inflammation:

  • Activates histamine and bradykinin

  • Dilates blood vessels, increases vascular permeability, and sensitizes nerve endings

Analgesic and Antipyretic Effects:

• Analgesia occurs peripherally and at the level of the brain (depresses pain stimuli)

• Antipyretic effect blocks the hypothalamic response to prostaglandin to "reset the thermostat"

Decreased Platelet Aggregation:

• NSAIDs inhibit the enzyme cyclooxygenase (COX)

• Two forms found in peripheral tissue: COX-1 and COX-2

  • COX-1 participates primarily in normal daily cell function

  • COX-2 is induced by inflammation

  • (Note: there are many exceptions to this general rule)

• NSAIDs that effectively inhibit COX-1 are more likely to cause platelet inhibition

Arachidonic Acid Pathway

	COX-1	COX-2
Location	Stomach, platelets	Sites of inflammation
Produces	Cytoprotective PGs	Inflammatory PGs

COX-1 Prostaglandins:

• Maintain good blood flow to the stomach and upper GIT

• Decrease HCl production in the stomach

• Increase secretion of stomach-protecting mucous

• Maintain good blood flow to the kidneys

COX-2

is responsible for the inflammatory response:

• NSAIDs that more preferentially inhibit COX-2 have fewer side effects (e.g., decreased GI side effects)

Uses: Analgesia

• Surgical, trauma, arthritis, musculoskeletal

• Ideally given before the onset of inflammation and pain

• Analgesic effects: rapid onset and short duration when compared to anti-inflammatory effects

• Not all NSAIDs are created equal — some have better analgesic effects than others

Uses: Antipyretic

• Bacterial infections

Uses: Anti-inflammatory

• Musculoskeletal, arthritic, trauma, post-op

• Septic shock

Uses: Anti-thrombotic

• CHF

• IMHA

• Heartworm adulticide treatment

NSAIDs — Toxicities / Adverse Effects

• Gastric irritation and ulceration

  • Phenylbutazone is very irritating if injected SQ or IM

• Nephrotoxicity

• Decreased platelet aggregation

• Decreased metabolism and excretion in cats

• Ibuprofen is contraindicated in small animals

• Hepatotoxicity reports with carprofen in dogs