Canis ISSN: 2398-2942

Therapeutics: musculoskeletal system

Contributor(s): James Cook, Peter Hanson, Lauren Trepanier, Vericore Veterinary Products

Non-steroidal anti-inflammatory drugs (NSAIDs)

* Indicates drug 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 in certain situations.
    • COX-2 is mainly inflammatory. Some physiologic activity has been described (renal fluid balance, uterine implantation, wound healing, including gastric ulcer healing).
    • COX-3 is a splice variant of COX-2 and is mainly central in location.
  • Classification of NSAIDs:
    • Nonselective: inhibit COX-1 and COX-2 at approximately equal potencies.
    • COX-2 preferential: inhibit COX-2 to a greater degree but still have inhibition of COX-1.
    • COX-2 selective: inhibit only or predominantly COX-2 at therapeutic concentrations.
  • At least one NSAID also inhibits lipoxygenase (LOX) and may be considered a dual inhibitor (COX and LOX).
  • 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 concentrations.
  • Additional actions: inhibition of superoxide radical generation, blockade of lysosomal and non-lysosomal enzyme release (some have anti-bradykinin effects).
  • Toxicity varies with species sensitivity, mechanism of action, and individual drug properties.
  • Aspirin is unique in its covalent bonding → irreversible COX-1 inhibition.
  • Most NSAIDs are well absorbed PO.
  • Most NSAIDs are highly bound to plasma proteins, but still exhibit 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

  • For analgesic and anti-inflammatory action in acute inflammatory conditions; control of pain following surgery (some drugs comparable in this action with opioid analgesics Analgesia: opioid ).
  • Arthritides (osteoarthritis Arthritis: osteoarthritis ).
  • Aspirin used to prevent platelet aggregation in thrombo-embolic disorders. Can promote bleeding so contraindicated prior to surgery.
  • Use in aged animals depends on underlying renal and liver function. As with all drugs, use of NSAIDs should include appropriate patient selection.

Side-effects

  • Most commonly observed is gastrointestinal irritation (vomiting and diarrhea), with potential for ulceration, especially if concurrent use with corticosteroids.
    Do NOT give concurrently with corticosteroids
  • May cause acute renal failure if administered to hypotensive/hypovolemic patients because NSAIDs block production of reno-protective prostaglandins (both COX-1 and COX-2).
  • May see hepatotoxicity (rare acute hepatic necrosis reported with carprofen); may be teratogenic if given repeatedly during pregnancy.
  • Acetaminophen/paracetamol Paracetamol *: may act by inhibition of COX-3, but this is controversial. No anti-inflammatory activity but has been used as an analgesic and anti-pyretic.
  • Aspirin Acetyl salicylic acid : classic nonselective NSAID. Tends to be irritating to GI tract. Permanently interferes with platelet thromboxane production for the life of the platelet.
  • Carprofen Carprofen : preferential for COX-2.
  • Deracoxib Deracoxib : selective for COX-2; approved at two dose rates, one for surgical use and the other for osteoarthritis.
  • Dipyrone Dipyrone *: believed to act by inhibition of COX-3. Not recommended for use in dogs with availability of safer approved products.
  • Etodolac: nonselective to mildly preferential for COX-2.
  • Firocoxib Firocoxib : selective for COX-2 with little to no COX-1 activity.
  • Flunixin Flunixin meglumine : nonselective NSAID, tends to have more GI irritation and renal effects, not generally recommended in dogs as there are better alternatives available.
  • Ketoprofen Ketoprofen : nonselective NSAID; approved at two dose rates, one for short-term use and the other for long-term use.
  • Meloxicam Meloxicam : preferential for COX-2.
  • NaproxenNaproxen poisoning : nonselective NSAID, tends to have more GI irritation, not recommended in dogs.
  • Phenylbutazone Phenylbutazone : nonselective NSAID, tends to have more GI irritation, not recommended in dogs.
  • Tepoxalin: dual COX/LOX inhibitor. Cyclo-oxygenase activity is mainly COX-1 and persists longer than LOX inhibition.
  • Tolfenamic acid Tolfenamic acid : nonselective NSAID. Not used in the US.
  • Vedaprofen Vedaprofen *: nonselective NSAID. Not used in the US.

Other joint modifying agents

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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.
  • Bergh M S & Budsberg S C (2005)The Coxib NSAIDs: Potential Clinical and Pharmacologic Importance in Veterinary Medicine. J Vet Intern Med19, 633-643.


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