Non-steroidal anti-inflammatory drugs
NSAIDs inhibit the enzyme cyclo-oxygenase, thus reducing the biosynthesis of prostaglandins, mediators of pain and inflammation.
In general, NSAID do not inhibit lipoxygenase (and hence leukotriene) formation or the formation of other inflammatory mediators. The exception to this is the NSAID tepoxalin, a recently introduced NSAID.
Cyclo-oxygenase is present in the body in two forms COX-1 and COX-2. In the past it was thought that COX-1 catalyzed the formation of constitutive or housekeeping prostaglandins, which mediate a variety of normal physiologic effects including hemostasis, protection of the gastrointestinal mucosa and the kidney. In contrast, COX-2 was thought to be only activated in damaged and inflamed tissues and to catalyze the formation of inducible prostaglandins, including prostaglandin E2 (PGE2) as well as being involved in thermoregulation and in the pain response to injury. However, this is an oversimplification and it is now known that both COX-1 and COX-2 (in the brain, spinal cord, ovary, and kidney) have house keeping functions.
Most NSAID are reversible competitive COX inhibitors; their duration of inhibition is primarily determined by the elimination pharmacokinetics of the drug. The exception is aspirin which is an irreversible inhibitor of COX.
Inhibition of COX by NSAIDs produces their well known antipyretic, analgesic, and anti-inflammatory actions. However, inhibition of the housekeeping forms of the enzyme can result in unwanted effects of NSAID such as gastric ulceration and renal toxicity.
Gastrointestinal ulceration is the most common side effect of the NSAIDs. Horses may develop oral, lingual, or gastric ulceration with accompanying signs of colic, weight loss, or loose manure. In addition, an idiosyncratic predisposition for ulceration of the right dorsal colon has been associated with NSAID therapy in horses. Blood dyscrasias after long-term NSAID therapy have been reported in cats, dogs, and horses. Nephropathies associated with chronic NSAID use are common in humans. Animals with underlying renal compromise receiving NSAID could experience exacerbation or decompensation of their disease. It is important to maintain hydration and renal perfusion in animals receiving NSAID, especially those undergoing anesthesia or surgery. Hepatic dysfunction or failure have been reported in dogs (acetaminophen, carprofen, etodolac), and horses (phenylbutazone). NSAID should be used with caution in animals with preexisting hepatic disease.
The use of NSAID for the relief of perioperative pain in companion animals is increasing. In general, NSAID provide only symptomatic relief from pain and inflammation and do not significantly alter the course of pathologic damage. As analgesics, they are generally less potent than opioids and are therefore more effective against mild to moderate pain. Only injectable agents containing modern NSAIDs are considered here. Only Carprofen and Meloxicam are approved for administration before surgery.
- Tolfenamic acid