Toxicology of nonsteroidal antiinflammatory drugs

Nonsteroidal antiinflammatory drugs (NSAIDs) constitute a class of pharmacologically active agents with similar therapeutic actions and side effects, despite diverse chemical structures. NSAIDs inhibit the enzyme cyclo-oxygenase and, thus, decrease inflammation mediated by prostaglandins. Toxicoses due to NSAIDs are manifested primarily by gastrointestinal upset and hemorrhage and by renal damage. Management consists of detoxification measures, in addition to supportive and symptomatic care. The article outlines the incidence, clinical toxicity, mode of action, and pharmacokinetics of nonsteroidal antiinflammatory drugs. The toxic effects of NSAIDs on individual organ systems are described, and general management recommendations for the treatment of NSAID toxicoses are presented.     

Pharmacology and therapeutics of nonsteroidal antiinflammatory drugs in the dog and cat: 1 General pharmacology

The inflammatory process is described with particular reference to the cardinal signs, the microcir-culatory changes and the mediators and modulators of inflammation. Mediators and modulars comprise targets for therapeutic intervention; and the arachidonic acid pathway, generating the eicosanoid group of compounds, is considered in detail. Most non-steroidal anti-inflammatory drugs (NSAIDs) of both carboxylic and enolic acid subgroups act partly and in some cases perhaps soley through inhibition of the enzyme cyclo-oxy-genase which is concerned with the generation of an important subgroup of eicosanoids, the prostaglandins. The wanted (therapeutic) and unwanted (side-effects) actions of NSAIDs are considered together with their pharmacokinetic properties. The clinical pharmacology and therapeutic uses of NSAIDs in dogs and cats are described.     

Recent developments in ectoparasiticides

The sales and use of ectoparasiticides for the control of arthropod parasites of domestic animals constitute a major sector of the global animal health market. Animals are infected by a number of parasitic insect and acarine species causing major economic losses in production livestock, intense irritation and skin disease in companion animals, or public health issues, including bites of humans or zoonotic disease transmission. Dog and cat fleas, for example, can be a serious source of both animal and human irritation, which has led to a rapid expansion in the development of flea control products. The control of ectoparasite infections of veterinary importance still relies heavily on the use of chemicals that target the arthropod nervous system. Such compounds have suffered from a number of drawbacks, including the development of resistance and concerns over human and environmental safety. The search for safer technologies has, however, been hindered by the limited number of active target sites present in arthropods and, to some degree, by the ever-increasing costs of research and development of compounds with novel modes of action.This review provides a background to the currently available groups of ectoparasiticide compounds used in veterinary medicine and highlights some of the more recent developments including the introduction of insect growth regulators and new and improved methods of product application.     

非甾体抗炎药的研究进展

传统非甾体抗炎药对环氧化酶的选择性较差,副作用明显,临床应用受限.近年来,一些疗效好、副作用低的新型非甾体抗炎药相继问世,应用于临床.本文主要综述了选择性COX-2抑制剂、一氧化氮释放型非甾体抗炎药以及选择性5-LOX/COX-2双重抑制剂三类非甾体抗炎药中的代表药物的研究进展.     

Evaluation of the palatability of three nonsteroidal antiinflammatory top-dress formulations in horses

The efficacy of top-dress antiinflammatory drugs ultimately depends on a patient's willingness to consume treated feed. The current study compares the palatability of two phenylbutazone top-dress formulations (Equipalazone Powder, Dechra Pharmaceuticals, and Pro-Dynam, VetXX, Ltd.) and a suxibuzone top-dress formulation (Danilon Equidos, Janssen Animal Health). Results of a three-period, crossover study on 18 healthy horses showed that Pro-Dynam was significantly less palatable, with significantly less consumption of treated feed compared with either Equipalazone Powder or Danilon Equidos. There was no statistically significant difference in terms of consumption of treated feed and palatability scores between Equipalazone Powder and Danilon Equidos.     

Nonsteroidal antiinflammatory drugs: a review

The increasing use of nonsteroidal antiinflammatory drugs (NSAIDs) in small animals has resulted in the development of new and innovative additions to this class of drugs. Examples of NSAIDs now available for use in small animals include aspirin, etodolac, carprofen, ketoprofen, meloxicam, deracoxib, and tepoxalin. The purposes of this article are to review the pathophysiology of prostaglandin synthesis and inhibition, the mechanisms of action, pharmacokinetics, pharmacological effects, and potential adverse reactions of aspirin and the newly released NSAIDs.     

Development of in vitro assays for the evaluation of cyclooxygenase inhibitors and predicting selectivity of nonsteroidal anti-inflammatory drugs in cats

OBJECTIVE: To develop and validate in cats suitable in vitro assays for screening and ranking nonsteroidal antiinflammatory drugs (NSAIDs) on the basis of their inhibitory potencies for cyclooxygenase (COX)-1 and COX-2. ANIMALS: 10 cats. PROCEDURE: COX-1 and COX-2 activities in heparinized whole blood samples were induced with calcium ionophore and lipopolysaccharide, respectively. For the COX-2 assay, blood was pretreated with aspirin. The COX-1 and COX-2 assays were standardized, such that time courses of incubation with the test compounds and conditions of COX expression were as similar as possible in the 2 assays. Inhibition of thromboxane B2 production, measured by use of a radioimmunoassay, was taken as a marker of COX-1 and COX-2 activities. These assays were used to test 10 to 12 concentrations of a COX-1 selective drug (SC-560) and of 2 NSAIDs currently used in feline practice, meloxicam and carprofen. Selectivities of these drugs were compared by use of classic 50% and 80% inhibitory concentration (ie, IC50 and IC80) ratios but also with alternative indices that are more clinically relevant. RESULTS: These assay conditions provide a convenient and robust method for the determination of NSAID selectivity. The S(+) enantiomeric form of carprofen was found to be COX-2 selective in cats, but meloxicam was only slightly preferential for this isoenzyme. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro pharmacodynamic and in vivo pharmacokinetic data predict that the COX-2 selectivity of both drugs for cats will be limited when used at the recommended doses. This study provides new approaches to the selection of COX inhibitors for subsequent clinical testing.     

Recent developments in equine dentistry

ABSTRACT

Equine dentistry is a rapidly developing clinical specialty. It has benefitted from key advances in anatomical and physiological research, development of equipment and instrumentation, utilisation of standing sedation and anaesthesia protocols, a change towards minimally invasive surgical techniques, and the introduction of restorative and endodontic techniques translated from techniques used in human and canine dentistry. Anatomical research has provided further insight into the endodontic system of incisors and cheek teeth and how it changes throughout development with age. Studies of the periodontium have demonstrated a rich vascular supply and repair capacity. Routine dental visits are increasingly being performed utilising sedation and clinical instruments for routine examinations. Equipment has become more efficient, battery-operated and miniaturised giving benefits to both equine dental maintenance work and advanced techniques, assisting the transition to minimally invasive techniques, and the development of endodontic and restorative dentistry. Diagnosis has also benefitted from advances in equipment such as patient-side digital radiography systems, high definition oroscopy, and small diameter flexible fibrescopes that are capable of visualising inside a pulp canal. Dental units combining endodontic high- and low-speed drills, suction and air or water flush are becoming increasingly used and adapted for equine use. Sedative combinations and standing anaesthesia protocols have meant that revisions of traditional techniques, as well as novel techniques, can be performed with almost no requirement for general anaesthesia. Equine dentistry can only continue to advance in this way if there is early identification of dental disease through clinical oral examinations, leading to a system based on prophylaxis, as in human dentistry. This necessitates a change in attitude of the public and industry in general to a proactive approach, with early intervention based on examination and diagnostic findings of practitioners and not necessarily based on the clinical signs displayed by the patient.     

Recent developments in fish vaccinology

During the last 10 to 20 years vaccination has become established as an important method for prevention of infectious diseases in farmed fish, mainly salmonid species. So far, most commercial vaccines have been inactivated vaccines administered by injection or immersion. Bacterial infections caused by Gram-negative bacteria such as Vibrio sp., Aeromonas sp., and Yersinia sp. have been effectively controlled by vaccination. With furunculosis, the success is attributed to the use of injectable vaccines containing adjuvants. Vaccines against virus infections, including infectious pancreatic necrosis, have also been used in commercial fish farming. Vaccines against several other bacterial and viral infections have been studied and found to be technically feasible. Pasteurellosis, streptococcosis (lactococcosis) and infections with iridoviruses are candidate diseases for control by immunoprophylaxis in the near future. The overall positive effect of vaccination in farmed fish is reduced mortality. However, for the future of the fish farming industry it is also important that vaccination contributes to a sustainable biological production with negligible consumption of antibiotics. A potential side-effect associated with injectable vaccines is local reactions in the peritoneal cavity. The paper presents recent developments in immunoprophylaxis of fish and some problems that should be addressed by the research community in the years to come.     

Recent developments in veterinary vaccinology

Advancement in technology and science and our detailed knowledge of immunology, molecular biology, microbiology, and biochemistry among other basic science disciplines have defined new directions for vaccine development strategies. The applicability of genetic engineering and proteomics along with other new technologies have played pivotal roles in introducing novel ideas in vaccinology, and resulted in developing new vaccines and improving the quality of existing ones. Subunit vaccines, recombinant vaccines, DNA vaccines and vectored vaccines are rapidly gaining scientific and public acceptance as the new generation of vaccines and are seriously considered as alternatives to current conventional vaccines. The present review focuses on recent advances in veterinary vaccinology and addresses the effects and impact of modern microbiology, immunology, and molecular biology.     

Clinical pharmacology of nonsteroidal anti-inflammatory drugs in dogs

OBJECTIVES: To discuss the clinical pharmacology of currently licensed veterinary NSAIDs and to review gastrointestinal and renal adverse effects as well as drug-drug interactions that have been reported with these drugs. To review the use of NSAIDs in the peri-operative setting and their use in patients with osteoarthritis. To further review the reported effects of NSAIDs on canine articular cartilage and liver as well as the clinical relevance of a washout period. DATABASES USED: PubMed, CAB abstracts and Google Scholar using dog, dogs, nonsteroidal anti-inflammatory drugs and NSAID(s) as keywords. CONCLUSIONS: A good understanding of the mechanisms by which NSAIDs elicit their analgesic effect is essential in order to minimize adverse effects and drug-drug interactions. Cyclooxygenase (COX) is present in at least two active isoforms in the body and is the primary pharmacologic target of NSAIDs. Inhibition of COX is associated with the analgesic effects of NSAIDs. COX is present in the gastrointestinal tract and kidneys, along with other areas of the body, and is also the likely reason for many adverse effects including gastrointestinal and renal adverse effects. The newer veterinary approved NSAIDs have a lower frequency of gastrointestinal adverse effects in dogs compared to drugs such as aspirin, ketoprofen and flunixin, which may be due to differential effects on the COX isoforms. There are currently no published reports demonstrating that the newer NSAIDs are associated with fewer renal or hepatic adverse effects in dogs. NSAIDs remain the cornerstone of oral therapy for osteoarthritis unless contraindicated by intolerance, concurrent therapies or underlying medical conditions. NSAIDs are also effective and frequently used for the management of post-operative pain.     

Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs in canine blood

OBJECTIVE: To evaluate cyclooxygenase (COX) selectivity of several nonsteroidal anti-inflammatory drugs (NSAID) in canine blood in vitro. ANIMALS: 11 healthy adult male hound crosses. PROCEDURE: 9 NSAID were studied at 5 concentrations. Thromboxane B2 (TxB2) was assayed as a measure of COX-1 activity in clotted blood. Prostaglandin E2 (PGE2) was assayed as a measure of COX-2 activity in heparinized, lipopolysaccharide (LPS)-stimulated blood. All assays were competitive ELISA tests. Cyclooxygenase selectivity was expressed as a ratio of the concentration of an NSAID that inhibited 50% of the activity (IC50) of COX-1 to the IC50 of COX-2. A separate ratio of the concentration that inhibited 80% of COX activity (IC80) was also determined. A ratio of < 1.0 indicated selectivity for COX-1, whereas a ratio of > 1.0 indicated COX-2 selectivity. RESULTS: Ketoprofen, aspirin, and etodolac were COX-1 selective. Piroxicam, meloxicam, and carprofen had COX-2 selectivity. The IC50 and IC80 values were similar for most NSAID. CONCLUSIONS: This methodology provides repeatable data from individual dogs and is comparable to results of previous in vitro and ex vivo models. Findings are also consistent with those of canine studies performed in vivo, suggesting that this is a viable in vitro assessment of the COX selectivity of NSAID in dogs.     

蜂胶的最新研究进展

本文总结了蜂胶药理学研究的最新进展，讨论了由于蜂胶化学成分差异性而引起的生物学研究的问题，概述了近期蜂胶研究的进展及趋势，即对化学特性已知蜂胶的生物学研究、生物活性原理研究、不同来源和不同化学组成蜂胶的比较生物学研究。这些研究对于制订蜂胶的质量标准和在医疗中的实际应用具有参考价值。同时，这些研究将蜂胶的特定化学成分与其生物活性联系起来，对从业者具有重要意义。