Felis ISSN 2398-2950

Therapeutics: musculoskeletal system

Contributor(s): Kyle Braund, Peter Hanson, Lauren Trepanier, Vericore Veterinary Products

Non-steroidal anti-inflammatory drugs (NSAIDs)

  • * Indicates product not licensed for this use in this species.

Action

  • Properties:
    • Anti-pyretic.
    • Anti-inflammatory.
    • Analgesic.
    • +/- Anti-endotoxemic.
    • +/- Anti-thrombotic.
  • Mechanism of action: most inhibit cyclo-oxygenases (COX).
  • There are three or more isoforms of COX:
    • COX-1 is mainly physiologic (gastric protection, renal blood flow, clotting activity). Some inflammatory activity has also been described.
    • COX-2 is mainly inflammatory. Some physiologic activity has been described (renal fluid balance, uterine implantation, wound healing, including healing of gastric ulcers).
    • COX-3 is a splice variant of COX-1 and is mainly central in location.
  • Classification of NSAIDs:
    • Nonselective: inhibit COX-1 and COX-2 at equal levels.
    • COX-2 preferential: inhibit COX-2 to a greater degree but still have some inhibition of COX-1.
    • COX-2 selective: inhibit only or predominantly COX-2 at therapeutic levels.
  • None of the NSAIDs at therapeutic levels inhibit the relevant enzyme(s) 100% continuously. There is a time course of inhibition based on tissue drug level.
  • Additional actions: inhibition of superoxide radical generation, blockade of lysosomal and non-lysosomal enzyme release (some have anti-bradykinin effects).
  • Toxicity varies with species, mechanism of action, and individual drug properties.
  • Therapeutic index in cats is generally less than that in dogs. Cats are particularly sensitive to gastrointestinal irritation/ulceration and renal compromise.
  • Many NSAIDs are metabolized by glucuronidation. Cats have decreased glucuronidation activity for xenobiotics compared with other species. This leads to prolonged effects of most NSAIDs in cats.
  • Aspirin is unique in its covalent bonding    →   irreversible enzyme blockade: to prevent platelet aggregation in thrombo-embolic disorders.
  • Most NSAIDs are well absorbed PO.
  • Most NSAIDs are highly bound to plasma proteins, but have good penetration of inflammatory exudates (since plasma proteins extravasate).
  • Tissue bound drug cleared more slowly than plasma protein bound drug and acts as reservoir.

Use

Few products officially approved for use in cats.

  • Duration of recommended use in cats is typically short, eg 1-3 days, because of lack of safety data for chronic administration.
  • Daily dosage in cats is typically lower and with less frequent intervals than dogs.
    Do not assume dog dosage applies to cats.
  • For analgesic and anti-inflammatory action in acute inflammatory conditions; control of pain following surgery (some drugs comparable in this action with opioid analgesics); anti-pyretic.
  • Arthritides; less recognized than in dogs but still exists in cats.
  • Anti-thrombotic effects of NSAIDs that inhibit COX-1 (eg for thrombo-embolic disease such as saddle thrombus).
  • Use in aged animals depends on renal and hepatic function.
  • As with all drugs, use of NSAIDs should include appropriate patient selection.

Side-effects

  • Gastrointestinal irritation and ulceration are the most common side-effects.
  • May cause acute renal failure if administered to hypotensive/hypovolemic patients because NSAIDs block production of reno-protective prostaglandins.
    Use caution if given pre-operatively.
  • Vomiting, blood dyscrasias, hepatotoxicity, renal papillary necrosis, skin rashes; may be teratogenic if given repeatedly during pregnancy.
  • Aspirin*:used to prevent thromboembolism in cats (efficacy data lacking). Significant COX-1 inhibition.
  • Carprofen  Carprofen  : used off label as a single dose. COX-2 preferential.
  • Deracoxib*: use based on published literature. COX-2 selective.
  • Firocoxib*: use based on published literature. COX-2 selective.
  • Meloxicam  Meloxicam  : approved as single dose in cats in the US/Canada and UK, and for chronic oral administration in cats in UK and Australia. COX-2 preferential.
  • Ketoprofen  Ketoprofen  : approved for up to 5 days as a tablet or injectable.
  • Tolfenamic acid  Tolfenamic acid  : approved for 3-5 days as a tablet.

Other anti-inflammatory drugs

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Topical anti-inflammatory preparations

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Cytotoxic immunosuppressants and disease-modifying drugs

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Further Reading

Publications

Refereed papers
  • Recent references fromPubMed.
  • Gunew M N et al(2008)Long-term safety, efficacy and palatability of oral meloxicam at 0.01-0.03 mg/kg for treatment of osteoarthritic pain in cats. J Feline Med Surg10(3), 235-241PubMed.
  • Gassel A D, Tobias K M & Cox S K (2006)Disposition of deracoxib in cats after oral administration. JAAHA42(3), 212-217PubMed.
  • McCann M E, Rickes E L, Hora D F, Cunningham P K, Zhang D, Brideau C, Black W C & Hickey G J (2005)In vitro effects and in vivo efficacy of a novel cycooxygenase-2 inhibitor in cats with lipopolysaccharide-induced pyrexia. Am J Vet Res66(7), 1278-1284PubMed.
  • Behrend E N et al(1997)Glucocorticoid therapy - Pharmacology, indications, and complications. Vet Clin North Am Small Anim Pract27(2), 187-213 PubMed.


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