A rational approach to osteoarthritis management (Proceedings) - Veterinary Healthcare
  • SEARCH:

ADVERTISEMENT

A rational approach to osteoarthritis management (Proceedings)


CVC IN BALTIMORE PROCEEDINGS


NSAIDs

New discoveries regarding inflammatory mediators and biochemical mediators associated with osteoarthritis have led to an increased understanding and use of NSAIDs in veterinary osteoarthritis management. It is now recognized that there are at least three different cyclooxygenase (COX) enzymes (COX-1, COX-2, and a COX-1 variant called COX-3) which are active in the metabolism of arachadonic acid. Certain NSAIDs may have selectivity in their actions against these isoenzymes. Furthermore, there is data to support that the ratio of COX and lipoxygenase (LOX) inhibition may be important in the improved gastrointestinal safety seen in dogs, and a dual COX/LOX inhibitor has been introduced to the market.

Pharmacokinetics and Mechanisms of Action

NSAIDs produce analgesia and toxic side-effects primarily by inhibiting COX, a key enzyme in the arachadonic acid (AA) pathway, and ceasing the production of prostaglandins, most notably prostaglandin E2 (PGE2). Two isoforms of the COX enzyme have been intensely investigated: a constitutive COX-1, responsible for normal physiologic functions; and an inducible COX-2, associated with inflammation and pain. Theoretically, an NSAID that selectively inhibits COX-2 without affecting COX-1 will allow analgesia without the common side effects of COX-1 inhibition, which include altered gastrointestinal and thrombocyte function.

An NSAID's ability to inhibit each COX enzyme is often reported as a ratio, which defines enzyme selectivity based on in vitro testing. While some drugs are now marketed as COX-2 preferential, bottom line is all NSAIDs are COX-2 inhibitors. What is different is how the newer compounds do not concomitantly inhibit COX-1. Thus it is probably better to consider these products as COX-1 sparing. Coxibs are a subclass of NSAIDs with a specific molecular structure that confers high specificity, saturability, and reversibility in binding. Coxibs, like all NSAIDs, inhibit COX-2, but their important feature is their sparing effect on COX-1.

In addition, extensive data exists which indicate that many of the anti-inflammatory effects of NSAIDs are unrelated to the inhibition of arachadonic acid metabolism. NSAIDs have been shown to inhibit a variety of neutrophil functions, and there is strong evidence to support that NSAIDs act directly in the spinal cord and higher centers.

Indications

NSAIDs can be used to treat acute pain, either traumatic or surgically induced, as well as chronic pain such as in osteoarthritis. There is evidence that NSAIDs are effective in treating certain neoplasias and potentially certain central nervous system disorders. It is wise to use products with a history of extensive clinical experience and good safety profiles. Always use only one NSAID at a time and ensure adequate dosing. Review therapy frequently, and change to alternative NSAIDs if there is a poor response to therapy. Observe for potential toxicity as soon as administration is begun with increased vigilance and monitoring required for at-risk patients. If indicated, establish renal and hepatic status of the patient prior to NSAID administration. Remember, efficacy and toxicity is often individualistic and individual monitoring is mandatory.

Contraindications

One must adapt therapy to suit the patient's requirements. In patients with chronic disease, begin with the recommended dose, and if efficacious, attempt to reduce dose at regular intervals (ex. weekly) until you have the lowest dose providing the maximum benefit. In patients with the following conditions, NSAIDS should be avoided or given judiciously and under close supervision: renal or hepatic insufficiency, decreased in the circulating blood volume (e.g. shock, dehydration, hypotension, or ascites), confirmed or suspected coagulopathy (this may be less important with COX-1 sparing drugs), active GI disease, traumatic injury with known or suspected significant active hemorrhage or blood loss, pregnancy, and significant pulmonary disease (this may be less important with COX-1 sparing drugs).


ADVERTISEMENT

Source: CVC IN BALTIMORE PROCEEDINGS,
Click here