Practically all non steroid anti-inflammatory drugs (NSAIDs) produce analgesia by inhibitory action on cyclooxygenase (COX) family of enzymes preventing production of prostaglandins and thromboxanes.
Because of effect on prostaglandin production, reduce inflammation, fever and endotoxemia and may inhibit aggregation of platelets.
Can be used in the treatment of chronic pain.
Although many effects of NSAIDs are beneficial in inflammatory conditions, also have some undesirable effects.
Toxic effects caused mostly by inhibition of production of the types of prostaglandins that protect homeostasis of kidneys and gastrointestinal tract.
Toxic side-effects include:
Gastric irritation, progressing to vomiting, ulceration and hemorrhage.
Enteritis leading to diarrhea and melena.
Blood dyscrasias.
Hepatotoxicity or nephrotoxicity .
Nephrotoxicity much more likely to occur in dogs that are dehydrated, hypotensive or hypovolemic. Adequate fluid therapy should be provided before NSAIDs are administered in these cases.
Use NSAIDs with care in dogs undergoing anesthesia because hypotension frequently occurs. However, if IV fluids are administered and blood pressure is monitored, NSAIDs are safe to use during the peri-operative period.
Do not give NSAIDs and corticosteroids simultaneously because side-effects much more likely to occur. Particularly the case for gut ulceration .
Do not use more than one NSAID at the same time because of increased risk of toxic effects. If one NSAID is not effective and veterinarian chooses to use a different one, there should be a washout period of 48 h - 2 weeks, depending on the type of NSAID used initially.
From a historical standpoint, two classes of cyclooxygenase enzyme exist:
COX1 enzymes have a protective function and are active continuously. They regulate renal blood flow (autoregulation) and protect gut mucosa. Also active on platelets, brain and spinal cord.
COX2 enzymes are expressed at sites of inflammation and were thought to be otherwise inactive. Involved in production of various mediators that cause pain, swelling, etc.
Quite recently, a third class (COX3) has been identified.
Older NSAIDs eg aspirin and phenylbutazone are non specific and will inhibit both classes of COX. Therefore, while being useful in inflammation, can cause gut ulceration , nephrotoxicity , etc. Some NSAIDs such as carprofen are more selective for COX2 enzyme and so are less likely to cause undesirable side effects.
More recent development is coxib class of NSAID (Deramaxx, Novartis) which has a specific structure that blocks only COX2 enzymes and so spares the COX1. Was considered to allow much greater safety for gut and kidney and to not be associated with causing gut ulceration.
However, recently discovered that COX2 enzymes also have certain protective functions and so potential still exists for toxicity to these organ systems.
COX2 enzymes important in allowing healing of an ulcer by regulating blood flow to site. Administration of a COX2 inhibiting NSAID has been shown to delay ulcer healing in laboratory animals and is contraindicated in any animal with a pre-existing ulcer.
From a renal standpoint, COX2 inhibitors may impair renal function in dehydrated or hypovelemic animals. Treat animals with renal or hepatic disease with great care or not at all.
Another recent addition to NSAID group of drugs is tepoxalin which is formulated as fast dissolving tablets that can be placed inside the lip of dogs. Available for only a short time so very little information on its efficacy in a large clinical population. Drug blocks both cyclooxygenase and lipoxygenase pathways. Latter pathway leads to formation of leukotrienes which are also involved in inflammation.
Flunixin : may be particularly likely to cause renal failure and gastrointestinal ulceration in hypovolemic dogs.
Ketoprofen : excellent analgesic and antipyretic agent.
Meloxicam.
Carprofen : despite being a weak cyclo-oxygenase inhibitor, carprofen has proved to be a potent analgesic and anti-inflammatory agent. Extremely useful for providing pre-emptive analgesia when given as part of premedication or at induction of anesthesia. Occasionally associated with hepatotoxicity in dogs.
Deramaxx: COX1 sparing drug and very effective for arthritic pain with no adverse effects in laboratory trials. Not available in injectable form.
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Vetstream contributor(s)
Dr B D X Lascelles BSc, BVSc, PhD, CertVA, DASA(ST), DECVS, DACVS MRCVS Assistant Professor Small Animal Surgery, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
Dr Stephen Greene DVM MS DipACVA, University of Washington, Dept of Veterinary Clinical Sciences, College of Veterinary Medicine, Pullman, WA 999164-6610, USA.
Dr Cheryl A Blaze BVSc PhD MBA DipACVA DVA, Tufts University School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA.
Use NSAIDs with care in dogs undergoing anesthesia because hypotension frequently occurs. However, if IV fluids are administered and blood pressure is monitored, NSAIDs are safe to use during the peri-operative period.