COVID-19 update – OPEN FOR BUSINESS: To refer a case or book an appointment with one of our specialists, please contact us

  • NSAIDs, when to use them and when to avoid them

Nicki Grint
EBVS® European Specialist in Veterinary Anaesthesia & Analgesia and RCVS Specialist in Veterinary Anaesthesia
BVSc PhD DVA DipECVAA MRCVS

Introduction

dog

Non-steroidal anti-inflammatory drugs produce analgesic, anti-inflammatory and anti-pyretic effects, all mediated through the inhibition of prostaglandin production. Cyclo-oxygenase (COX) enzymes convert arachidonic acid into prostaglandins.

There are two distinct isoforms; COX-1, and COX-2.

COX-1 synthesizes prostaglandins that regulate normal homeostasis.

COX-2 intensifies the inflammatory response by forming prostaglandins that sensitise the peripheral nociceptors leading to localised pain and hypersensitivity.

Cyclo-oxygenase selectivity

Gastro-intestinal

The most common type of adverse events associated with NSAIDS are those involving the gastro-intestinal (GI) system. This is because of the inhibition of some constitutive prostaglandins which are involved in the protection of the gut mucosa by the following mechanisms:

  • Regulation of blood flow to the gut lining.
  • Stimulation of a bicarbonate layer to protect the gut lining from acid.
  • Production of a mucus layer to protect the gut surface.
  • Decreasing acid production

Gastro-intestinal erosion, ulceration or perforation can occur in animals which have previously had no signs of GI adverse effects.

Risk factors for developing GI toxicity with NSAID use are:

  • History of GI ulceration.
  • Geriatric patient as older dogs have a reduced drug clearance.
  • Co-morbidities of other GI diseases.
  • Impaired renal or hepatic function, or hypoproteinaemia.

Renal toxicity

Because both COX-1 and COX-2 are present in normal kidneys, any type of NSAID, whether COX-2 selective or not can cause renal toxicity or exacerbate renal insufficiency. This is due to the effects on prostaglandins which regulate renal blood flow. At times of hypovolaemia, dehydration, or hypotension the kidney relies on prostaglandins to preserve renal blood flow, and NSAIDS should be avoided in these situations.

cat

Prescription of NSAIDs in animals that already have renal insufficiency should be carefully considered as the use of NSAIDs has the potential to exacerbate the renal disease. The animal must be hydrated, and not hypovolaemic or hypotensive.

Gastro-intestinal erosion, ulceration or perforation can occur in animals which have previously had no signs of GI adverse effects.

There is evidence in cats with stable chronic kidney disease, that long term meloxicam (Gowan et al. (2011)) OR robenaoxib (Kongara & Chambers (2018)) analgesia at a low dose can be used to treat pain associated with degenerative joint disease without causing a progression of the renal disease.

Practical suggestions for starting the chronic use of NSAIDs in an animal with chronic kidney disease are as follows:

  • Ensure the patient is and stays well hydrated.
  • Monitor these patients regularly for hypertension and proteinuria (as both are prognostic indicators for potential renal adverse effects of NSAIDs) in addition to other markers of acute kidney injury.
  • Wean down to the lowest effective dose of the NSAID.
  • Consider alternative analgesics which have lesser effects on the renal system.

Hepatic toxicity

All NSAIDs are metabolised in the liver, and drug-induced hepatotoxicity is a serious but rare complication. In dogs, it has been reported after repeated use of carprofen producing a cytotoxic hepatocellular reaction. There is less evidence of hepatotoxicity in cats.

To support a diagnosis of hepatotoxicity, a three to four fold increase in hepatic enzymes above baseline within the first few days (up to two to four weeks) of starting NSAIDs alongside resolution of clinical signs and elevated biochemistry values after discontinuation, would be observed. Elevated baseline liver enzymes (e.g. those often seen in geriatric animals) are not a risk factor for developing a hepatotoxicity. If long term prescription is anticipated, baseline liver enzymes should be measured and then monitored after two weeks, and then periodically thereafter.

Use of NSAIDs with concurrent medications

The use of the following medications should be avoided with concurrent use of NSAIDs:

  • Highly protein bound drugs (e.g. phenobarbital, digoxin): as NSAIDs are also highly protein bound they may displace such drugs from their binding sites and alter their effects.
  • Drugs with potential nephrotoxicity (e.g. cisplatin) or that modify renal prostaglandins (e.g. diuretics, Ace-inhibitors).
  • Corticosteroids; these act at the level of phospholipase A2 and blocking the synthesis of prostaglandins at multiple levels will increase the chances of toxicities.
  • Other NSAIDs: concurrent administration of two different NSAIDs is not recommended. If an animal has had a poor response to a NSAID or has developed side effects, one further NSAID (ideally from a different class) can be tried, but a wash-out period based on 3-4 times the half life of the original NSAID needs to be allowed. If unknown, a minimum of 5-7 days should be allowed. If an animal has had evidence of side effects from two different NSAIDs, they should be identified as NSAID intolerant and no further drugs in this group should be offered.

Conclusion

In general, NSAIDs are effective analgesics and play an important part in the multi- modal approach to analgesia, especially if there is an inflammatory component to pain.

They should certainly be considered in patients that have:

  • known normal organ function,
  • are euhydrated and have normal water and food intake,
  • are normovolaemic.

For more information or to speak to one of our specialist Anaesthetists please call 01823 653510.