They’re used both for their central and their peripheral effects in many species, including dogs, cats, rabbits and small mammals. However, there are significant species differences in pharmacokinetics, so make sure you check the data sheets and evidence of safe use in your target species. Veterinary licenced NSAIDs are generally safe when compared to some of the common over the counter human preparations, but it’s important for us to be aware of their potential negative effects.
They work predominantly by inhibiting cyclooxygenases (COXs), which facilitate the production of prostaglandins involved in inflammation. COX1 is the form of the enzyme necessary for the regulation of physiological functions, whilst COX2 is the form synthesised at the place of inflammation. Only COX1 produces prostaglandins that activate platelets and protect the stomach and intestinal lining.
Ketoprofen and piroxicam are both COX1 selective, whilst meloxicam is more COX2 selective. Carprofen is a COX1 sparing NSAID, specifically inhibiting COX2 activity and providing analgesic, anti-inflammatory and antipyretic effects. COX2 specificity appears to be species, dose and tissue dependent.
What are the risks?
Serious side effects associated with the use of NSAIDs can occur with or without warning. Common side effects include;
- Gastrointestinal complications – these are the most common side effect we see, and include vomiting, diarrhoea and loss of appetite. Gastric ulceration occurs due to the inhibition of prostaglandin synthesis and a decrease in the production of mucosal protective substances. In some patients it’s possible for gastric inflammation and ulcers to be silent, so don’t be complacent or unaware.
- Renal disease – nephrotoxicity is related to the inhibition of prostaglandins present in kidneys, which are necessary for the regulation of electrolytes, blood flow and renin secretion. Vasoconstriction of the renal vessels and decreased renal blood flow can lead to acute renal failure.
- Drug interactions – there are some drugs that compromise the use of NSAIDs at the same time. Corticosteroids, furosemide and ACE inhibitors are examples, so always check current thinking and evidence. The simultaneous use of NSAIDs and ACE inhibitors has been associated with reducing the anti-hypertensive effects, as well as carrying the potential to cause acute renal failure. There are also some other potentially nephrotoxic drugs to avoid, such as aminoglycosides and cisplatin. Caution should be used with highly protein-bound drugs such as barbiturates, digoxin and cyclosporine.
- Incorrect dosing - the leading risk factors for gastrointestinal perforations are as a result of giving to much or too often. Weigh the animal carefully and dose according to the animal’s lean body weight rather than actual body weight. Stress the importance of this to the owner and don’t allow them to become casual about when or how to give the medication. Use the lowest effective dose for the shortest duration.
- Clotting – look out for interference with clotting mechanisms. Decreased coagulation is the result of the lack of thromboxane A2 in the platelets after using COX1 inhibitors. Ketoprofen and tolfenamic acid should be avoided in animals with potential bleeding disorders such as thrombocytopenia, as well as prior to or during surgery where haemorrhage may be a problem.
- Liver damage - hepatocellular necrosis has been reported with various NSAIDs but is actually rare. Pre-existing elevated liver enzymes are not a risk factor.
11 ways to reduce the risks of NSAIDs
- Check before use – there are numerous situations where NSAIDs might potentially exacerbate a problem, so always check the animal’s history before prescribing. For example, mild renal problems could turn into renal failure as a result of imprudent use of NSAIDs.
- Clinical examination – always perform a detailed examination of the animal, checking for evidence of any pre-existing conditions such as renal, liver or heart failure. Check body weight, body condition and evidence of polydipsia or polyuria.
- Laboratory investigations - appropriate tests should be used to establish a baseline of information before and during NSAID use. Patients at greatest risk for kidney problems are those that are dehydrated, on diuretic treatment or have pre-existing kidney, heart or liver problems. Haematology, biochemistry and electrolyte tests together with urinalysis should be used.
- Use the lowest dose for the shortest period of time – titrate to the lowest effective dose in most situations to give yourself the greatest safety margin. Calculate your dose on lean body weight.
- Inform and advise - providing client information that describes potential side effects, including any patient care leaflets provided by drug manufacturers together with instruction on when to stop medication. Ensure the owner reads the data sheets.
- Use in house care sheets - where possible, inform the owner verbally and give them your own practice information sheet regarding the use and risks of NSAIDs. Both you and the owner need to carefully consider the potential benefits and risks of using NSAIDs.
- Stop if there’s a problem – signs of toxicity usually show within 2 or 3 weeks but can occur at any at any time. Aim to recognise the earliest signs of harmful side effects and stop NSAID treatment immediately. This is particularly important in cases of gastrointestinal complications in dogs and cats with poor appetites.
- Care with anaesthetics – it’s vital to maintain normal blood pressure and circulation during anaesthesia, especially when using NSAIDs. Place a catheter and give intravenous fluids before, during and after an anaesthetic.
- Choose your patient carefully - avoid NSAIDs in patients with conditions associated with low blood flow, such as dehydration, hypovolaemia, heart failure, hypotension or renal disease.
- Use washout periods - consider withholding your chosen NSAID for 5 – 7 days prior to initiating treatment with another NSAID. If corticosteroids have been used, a longer washout period prior to using a NSAID may be necessary.
- Gastroprotection – proton pump inhibitors (e.g. omeprazole) and H2 antagonists such as cimetidine or ranitidine can be used to protect the stomach. If you use these protectants, make sure you follow the cascade.