Toxicology Brief: Naproxen toxicosis in dogs
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) used in people as an analgesic and antipyretic to treat multiple diseases including cancer, gout, arthritis, lupus, and musculoskeletal injuries. It is sold by prescription for human use as an oral suspension (25 mg/ml); 250-, 375-, and 500-mg tablets; and 750-mg extended-relief tablets, and is also sold over-the-counter as naproxen sodium in 220-mg tablets.1 In the past, naproxen was used as an extralabel drug in dogs, but most veterinarians currently prescribe NSAIDs labeled for use in dogs.2
PHARMACOKINETICS AND MECHANISM OF ACTION
Like other NSAIDs, naproxen blocks the enzyme cyclooxygenase to prevent the synthesis of prostaglandins. There are two commonly known forms of cyclooxygenase: COX-1 and COX-2. COX-1 is considered a constitutive enzyme, meaning it is always present. Prostaglandins formed by COX-1 are important for normal physiologic function. They protect both the gastrointestinal (GI) tract and the kidneys. COX-2 is an inducible enzyme. It plays a role in the formation of prostaglandins that mediate inflammation. Naproxen is a nonselective inhibitor of cyclooxygenases; therefore, it inhibits both COX-1 and COX-2.1
Prostaglandins formed by COX-1 protect the GI tract by inhibiting gastric acid secretions, increasing the production of bicarbonate by epithelial cells, increasing mucosal blood flow, and promoting epithelial cell repair and turnover. Loss of these protective prostaglandins can lead to GI tract irritation and ulceration.
In the kidney, protective prostaglandins act as vasodilators. They maintain adequate renal blood flow and glomerular filtration rate, mediate renin release, and are involved in electrolyte transfer. Therefore, a decrease in these prostaglandins can lead to adverse renal effects, including vasoconstrictive acute renal failure, acute interstitial nephritis, fluid and electrolyte abnormalities, and renal papillary necrosis.4