What are the adverse effects of NSAIDs?

1) GI ulceration - via inhibition of COX/PGE1 that normally promotes gastric mucus layer. LOX inhibition is gastroprotective however...

2) Hepatotoxicity - reversible and mild

3) Nephrotoxicity - via inhibition COX2 that causes vasodilation that allows for fluid elimination and secretion

4) Cardiovascular issues - via inhibition COX2/PGI2 that protects shape/integrity of vasculature and prevention of platelet aggregation. TXA2>PGI2

5) Drug interactions - Supplements GI ulceration of corticosteroid, Potentiates anticoagulants, Antagonizes antihypertensives, Nephrotoxic with aminoglycosides

Flunixin

Selectivity: Cox2 in horses, Cox1 in dogs

Uses: Analgesic (only visceral), Anti-inflammatory, Anti-pyretic in horse, cattle, and swine

Notes:

- Has the longest t1/2 for the horse (useful for colic)

- It's very good against endotoxicosis because it blocks the related PG-related events (esp when compounded with ketamine)

Acetaminophen

Selectivity: COX2 central (no peroxidases) and COX3

Indications: pCOX2 - weak antinflammatory

cCOX2 - analgesic effect

COX3 - antipyretic effect

Adverse Effects: hepatoxicity with high term dose

Ibuprofen

Not safe due to nephrotoxicity

Ketoprofen

Selectivity: Both COX and partial LOX

Indications: Short term use in horses

Adverse effects: Can prolong pregnancy

Carprofen

Selectivity: COX2 in dogs only

Indications: Inflammation

Adverse effects:

Reversible hepatotoxicity in Labs and other breeds

Can prolong pregnancy

Notes:

AKA Rimidyl

Cheap

Naproxen

Selectivity:Nonselective

Indications: Myositis in horses

Notes: Expensive

AKA Equiproxen and Naprosyn

Aspirin

Selectivity: Acetate: irreversible COX1 inhibitor

Salicylate: reversible COX inhibitor

Indications: Analgesia, anti-inflammatory, anti-pyretic, anti-coagulant

Adverse effects: Prolonged bleeding time (Platelets cannot make new COX1)

GI ulcers, inhibition of platelet activity

Species considerations:

Cats: dose every 72 hours

Dogs: Do not use for long-term osteoarthritis (sensitive chondrocytes)

Sheep: causes pulmonary edema

Salicylate

Phenylbutazone

Selectivity: COX-2

Indications: Musculoskeletal analgesic in horses with laminitis

Notes:

Banned in food producing animals

Approved in dogs, though not used any more

Horses develop tolerance

Piroxicam

Selectivity: COX2

Uses: Used as an adjunct versus bladder cancer in dogs

Note: should be used in conjuction with mioprostol, chemotherapy, and surgery/radiation

Meloxicam

Selectivity: COX2

Uses:Cats can only use single injections every 3 days

Adverse: Long term use results in renal failure in cats

Note:

Only COX2 selective approved for cats

Rofecoxib

Selectivity: Greatest COX2

Uses