Are COX-2 Selective NSAIDs Associated with Less GI, Renal, and Cardiovascular Side Effects: Evidence from Animals Treated with NSAIDs

Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to treat both acute and chronic pain in animals, especially when the pain is resulted from inflammatory conditions. NSAIDs work by inhibition of cyclooxygenases (COX) enzymes and reduce the production of key inflammatory mediators prostaglandins and associated chemicals. Prostaglandins have important roles in pain signalling and haemostasis, including platelet aggregation and gastric mucosal protection. There are two known isoforms of cyclooxygenases enzymes, namely COX-1 and COX-2. Notable adverse effects commonly resulted from NSAIDs uses include gastrointestinal ulceration, compromised haemostasis and renal toxicity, which are due to inhibition of COX-1 isoform. Despite the development of COX-2 selective medicines and continuing effort to improve the safety of NSAIDs in routine veterinary practice, adverse effects of NSAIDs still exist and require closed monitoring. This study aims to summarise and evaluate the current literature on reported adverse effects of NSAIDs used in animals and to compare COX-2 selective versus non-selective agents. Methodology: Literature on reported adverse effects of NSAIDs used in animals over the last decade has been systematically reviewed. Some older sources from the primary literature search have also been included to determine the background information leading to current rationale behind NSAIDs’ therapeutic uses, dosage and route of administration, observed adverse effects and COX-2 selective versus non-selective agents. The primary focus of this study is NSAIDs administered to animals in prospective randomised placebo-controlled blinded trials. Results: A total of 12 studies that met the inclusion criteria were included in the review, with total 13 NSAIDs being discussed, including meloxicam, phenylbutazone, deracoxib, carprofen, aspirin, firocoxib, vedaprofen, etorolac, ketoprofen, tepoxalin, rofecoxib, licofelone and flunixin. It was found that there were variable findings in comparing the adverse effects associated with COX-2 selective NSAIDs and non-selective NSAIDs. COX-2 selective NSAIDs have been found associated with no adverse effects in some studies and minimal adverse effects in other studies. Severe adverse effects were reported for COX-2 selective NSAID administered at higher than recommended doses or for a long duration and some studies reported reduced adverse effects in COX-2 selective NSAIDs when compared to non-selective NSAIDs. Overall, gastrointestinal adverse effects were predominantly reported, followed by adverse findings relating to haemostasis and renal function. Conclusion: Collectively, the findings suggest COX-2 selective NSAIDs provide a clinically useful improvement over non-selective NSAIDs as well as reduce adverse effects when given at recommended dose.

Drug Metabolism and Disposition in Australian Marsupial Koala (Phascolarctos cinereus)

Aims: Koalas are unique obligated eucalyptus feeding Australian marsupials that often require medical treatments after wildlife rehabilitation across Australia. At present, little is known about the pharmacology and pharmacokinetics of drugs commonly used in koalas and how koalas handle and detoxify toxic chemicals from both environmental exposure and their unique eucalyptus diet. The aim of this study is to summarise and critically evaluate the current literature on what is known about the pharmacokinetics (absorption, distribution, metabolism, and excretion ADME) of drugs frequently used in koalas, including antibiotics fluoroquinolones, fluconazole, chloramphenicol and analgesics. Methodology: Literature regarding drug disposition and pharmacokinetic studies of therapeutic agents commonly used in koalas over the last decade has been critically reviewed. Some older sources from the primary literature search have also been included to determine the background information leading to current rationale behind drug indication, dosage, and route of administration in marsupial koalas and related species. Results: Most studies reported a much lower bioavailability of orally administered drugs in koalas compared to that in humans and other species. Current dosing regimens do not prove to be effective or optimal in order to achieve the best treatment outcomes. It seems likely that oral administration of many drugs in koalas exhibited poor bioavailability due to poor absorption and might be extensive metabolism via hepatic and intestinal enzymes. Conclusion: Collectively, the findings suggest the need for further pharmacokinetic studies to investigate alternative routes of administration for many commonly used drugs in marsupial koalas, including antibiotics, anaesthetics, and analgesic medicines.

Non-Steroidal Anti-Inflammatory Drugs as Chemopreventive Agents: Evidence from Cancer Treatment in Domestic Animals

Aims: This study aims to systematically review currently available data on the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of cancer in domestic animals to evaluate the efficacy of different treatment protocols and to suggest further recommendations for future study. Methodology: Literature data on the use of NSAIDs in domestic animals as chemo-preventive agents in the last decade were collected and critically reviewed. Some older sources from the primary literature search have also been included to determine the background information leading to current rationale behind NSAID use in oncology. Results: In vitro inhibitions of tumour cell proliferation by both piroxicam and meloxicam have been demonstrated only at higher concentrations than those achievable in vivo. However, remission rates ranging from 7% to 71% have been observed when piroxicam is administered orally, either alone or in conjunction with other anticancer agents for treatment of transitional cell carcinoma of the urinary bladder of dogs. Piroxicam has also had positive results for multicentric lymphoma and nasal tumour, with remission rates of 79% and 75% respectively. In many cases, NSAID treatment showed increased median survival times and an improved quality of life of treated animals. Conclusion: NSAIDs have shown potential as an adjunctive therapy for the treatment of some cancers in domestic animals. This review highlights the major limitation of current studies on the role of NSAIDs in cancer treatment, including limited sample size in most cases and mainly by retrospective studies. A recommendation for future study is the investigation of multi-institutional animal trials to increase case numbers and allow for better statistical analysis with adequate control groups.

Management of Eastern Brown and Tiger Snake Envenomation in Domestic Animals in South Australia

Aims: The aims of this study were to examine the key important clinical features in domestic animals (e.g. dogs and cats) accompanying envenomation by eastern brown or tiger snakes in South Australia, to establish whether routine use of snake venom detection kits (SVDKs) is a useful diagnostic approach for identifying offending snake species and help to improve animal’s condition and survival. Methodology: Clinical records from 155 dogs and cats, with suspected or confirmed snake envenomation were collected from two veterinary practices in South Australia. Chi-square analysis was used to compare patient outcome with diagnostic method, and descriptive analysis were undertaken to compare features between the envenomation cases. Results: Brown snakes were responsible for 97% of cases, with the remaining 3% due to tiger snakes. The most common presenting signs were recumbency and hind limb paresis. Patients were 20% less likely to survive when diagnosis of the offending snake species was made by means other than the use of a SVDK. An inconclusive result occurred approximately 14% of the time when using a SVDK. The overall survival rate for cases that were treated was 81% in dogs and 92% in cats. Conclusion: Species-specific snake diagnosis using a SVDK will lead to improved patient outcome, however care is required when performing and interpreting the test due to a high proportion of contradictory results obtained.