Understanding NSAID use in dogs must include knowledge of mechanism of action in order to minimize adverse events. This review focused on clinical pharmacology, potential side effects, and drug–drug interactions. NSAIDs exert their effect through inhibition of cyclooxygenase (COX) enzymes (primarily COX-1 and COX-2). COX eicosanoid products (eg, prostaglandins, prostacyclin) are critical to the integrity of the gastric mucosa and renal blood flow. Although less prevalent with newer NSAIDs, GI side effects remain a concern. COX selectivity may not be clinically relevant in the diseased GI tract and has no proven benefit in the kidney and liver. Cases of NSAID-induced nephropathy are commonly associated with high doses or other complicating factors (eg, hypotension, hypovolemia). Hepatic side effects may be either dose dependent or idiosyncratic and appear to be related to production of reactive metabolites, not COX inhibition. Contraindications may include concurrent disease, volume or sodium depletion, and concurrent administration with antihypertensives. Adverse effects are well documented with concurrent use of multiple NSAIDs or NSAIDs with corticosteroids. A washout period is recommended when switching oral NSAIDs, but exact withdrawal times have not been determined. Caution, standard withdrawal times, and gastroprotective agents are advised when switching NSAIDs. NSAIDs were concluded to remain the mainstay of treatment for chronic canine osteoarthritis.
This article should be read by students in pharmacology courses, small animal clinicians, and residents preparing for board examinations, as it provided a critical review of studies that examined mechanisms of action, efficacy, and safety. The authors noted a lack of well-controlled comparisons of safety and efficacy among these drugs to guide medication selection. This article dispelled long-held assumptions about the actions of NSAIDs and critically examined the shortcomings in other NSAID studies. Advantages and disadvantages of drugs known to be COX-2 selective and whether these selective drugs have lived up to their promise are explained. The reader will not be provided a clear choice of which drug would be best for patients but will be more informed about this class of medication.—Mark G. Papich, DVM, MS, DACVCP
Clinical pharmacology of nonsteroidal anti-inflammatory drugs in dogs. KuKanich B, Bidgood T, Knesl O. VET ANAESTH ANALG 39:69-90, 2012.
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