Steroidal and non-steroidal anti-inflammatory drugs for wounds and traumatic inflammation

Abstract

Extract

Wounds of the skin and underlying tissues are common problems in both large and small animal practice, are frequently infected, and must therefore heal by granulation. This process is often impaired by movement, irritation, infection, necrosis, poor circulation, and even the inflammatory process itself. The latter, with its traditional cardinal signs, reflects the mobilization of the body's defences necessary for ultimate resolution. The as sociated pain, swelling, and interference with function may, however, have adverse effects. The clinician is thus faced with the need to maintain a delicate balance between adequate tissue defence, healthy granulation and repair on the one hand, and excessive or chronic inflammation, pain, swelling, impaired function, and circulation on the other. The therapeutic regimen, in addition to specific surgical procedures, should manipulate such target areas as etiologic factors, including those secondary to the initial insult, the mediators of inflammation, the non specific inflammatory process, and reparative processes. Such a regimen can well necessitate a “therapeutic cocktail”. During the last several years, work has been conducted on various anti-inflammatory (steroidal and non-steroidal) drugs, dimethyl sulphoxide (DMSO), and antihistamines(10) Jones, E. W. and Hamm, D. 1976. The Use of Naproxen in Horses. British Equine Journal (Pending),  [Google Scholar] (11) Kilian, J. G., Jones, E. W., Hamm, D., Riley, W. F. and Averkin, E. 1974. Proc. 20th Annual Mtg. Am. Assoc. of Equine Practitioners,  [Google Scholar]. This pharmacological polyglot, along with the complexity of inflammation, has created a need to clarify a confusing interaction and to justify the logic of utilizing such drugs either alone or in combination. It is in this context that controlled evaluations of parenteral and topical combinations of drugs in the horse, dog and cat have been conducted.     

Nonsteroidal anti-inflammatory drugs: a review. New applications in hypersensitivity reactions of cattle and horses.

Nonsteroidal anti-inflammatory drugs inhibit the biosynthesis of kinins and prostaglandins and stabilize leukocyte lysosomal membranes. Nonsteroidal anti-inflammatory drugs also weakly block the biosynthesis of histamine and serotonin, and pharmacologically antagonize kinins, prostaglandins and slow-reacting substance of anaphylaxis. Nonsteroidal anti-inflammatory drugs effectively control both cardiovascular and respiratory manifestations of hypersensitivity in cattle and horses. This, coupled with the contrasting lack of effectiveness of "antiamine" drugs, suggests that bio-amines such as histamine and serotonin (5-hydroxytryptamine) may be less important than kinins, postaglandins and slow-reacting substance in the mediation of the hypersensitivity/inflammatory reaction, at least in cardiopulmonary systems of these species. Nonsteroidal anti-inflammatory drugs justify more prominence in the clinical control of acute respiratory disease in domestic herbivores.     

Non-steroidal anti-inflammatory drugs in equine orthopaedics

Orthopaedic disorders are commonly encountered in equine veterinary medicine, and non-steroidal anti-inflammatory drugs (NSAIDs) play an important role in the management of many equine orthopaedic disorders. There are multiple NSAIDs available for use in horses, including both non-selective and selective NSAIDS, and the body of literature evaluating the efficacy of these medications, their effects on normal and inflamed musculoskeletal tissues, and their side effects is broad. This review aims to summarise the current literature on the use of NSAIDs for equine orthopaedic disorders and examines new and future avenues for the management of inflammation in equine orthopaedics.     

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.     

Development and validation of a new model of inflammation in the cat and selection of surrogate endpoints for testing anti-inflammatory drugs

In laboratory animals many models of inflammation have been developed for preclinical evaluation of the pharmacological profiles of nonsteroidal anti-inflammatory drugs (NSAIDs). In contrast, in species of veterinary interest, including the cat, NSAIDs have been studied mainly using dose-titration or dose-confirmation studies in clinical subjects. This is due to the scarcity of appropriate animal models and to the associated lack of quantitative validated endpoints describing the magnitude and time course of drug response. Determination of pharmacokinetic/pharmacodynamic (PK/PD) relationships provides a powerful approach for the selection of effective and safe dosage regimens. In this study, a paw inflammation model in the cat was developed for the preclinical evaluation of NSAIDs using PK/PD modelling. Subcutaneous injection of 500 mg kaolin in the paw produced a well-defined and reproducible inflammatory response that lasted 4-5 days. Several endpoints were assessed for their clinical relevance and for their metrological performance (accuracy and reproducibility). Body temperature, lameness scoring, locomotion tests and possibly skin temperature were the most appropriate endpoints for testing the antipyretic, analgesic and anti-inflammatory effects of NSAIDs in the cat.     

Nonsteroidal drugs used in the treatment of inflammation

An understanding of the basic mechanisms of inflammation aids in providing rational therapy to our patients. This article discusses both the inflammatory process and drugs used to reduce its intensity. The commonly used drug aspirin, as well as other less frequently employed medications, are described. There is an emphasis on clinical use of these agents, including appropriate dosages and precautions.     

Nonsteroidal anti-inflammatory drugs in veterinary ophthalmology.

Uveitis is a common sequela to many ocular diseases. Primary treatment goals for uveitis should be to halt inflammation, prevent or control complications caused by inflammation, relieve pain, and preserve vision.Systemic and topical NSAIDs are essential components of the pharmaceutic armamentarium currently employed in the management of ocular inflammation by general practitioners and veterinary ophthalmologists worldwide. NSAIDs effectively prevent intraoperative miosis; control postoperative pain and inflammation after intraocular procedures, thus optimizing surgical outcome; control symptoms of allergic conjunctivitis;alleviate pain from various causes of uveitis; and circumvent some of the unwanted side effects that occur with corticosteroid treatment. Systemic NSAID therapy is necessary to treat posterior uveitis, because therapeutic concentrations cannot be attained in the retina and choroid with topical administration alone, and is warranted when diseases, such as diabetes mellitus or systemic infection, preclude the use of systemic corticosteroids.Risk factors have been identified with systemic and topical administration of NSAIDs. In general, ophthalmic NSAIDs may be used safely with other ophthalmic pharmaceutics; however, concurrent use of drugs known to affect the corneal epithelium adversely, such as gentamicin, may lead to increased corneal penetration of the NSAID. The concurrent use of NSAIDs with topical corticosteroids in the face of significant preexisting corneal inflammation has been identified as a risk factor in precipitating corneal erosions and melts in people and should be undertaken with caution[8]. Clinicians should remain vigilant in their screening of ophthalmic and systemic complications secondary to drug therapy and educate owners accordingly. If a sudden increase in patient ocular pain (as manifested by an increase in blepharospasm, photophobia, ocular discharge, or rubbing)is noted, owners should be instructed to contact their veterinarian promptly.     

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.     

Factors determining the sward utilisation of winter pasture in cattle feeding

In this review article, factors determining the sward utilisation of winter pasture in cattle feeding were defined and analyzed. The results from literature and own investigations have shown that yield and quality of autumn-saved herbage on winter pasture are determined by pratotechnical measures such as harvest date in winter and pre-utilisation date in summer, botanical composition of sward, and particularly the dominated grass species or community, nitrogen fertilisation and weather conditions in winter. The date of winter harvest as a dominating factor affects the development of dry matter yield as well as the digestibility of organic matter and nutrients concentration in herbage during winter. For the management of winter grazing systems it could be obtained that crude protein and energy concentration of the tested autumn-saved herbage met the requirements of suckler cows or beef cattle until the end of the year if they were pre-utilised in July. The weather conditions during autumn-winter period are important factor determining the accumulation of secondary metabolites formed by field fungi in herbage of winter pasture.     

Nonsteroidal anti-inflammatory drugs in cats: a review

OBJECTIVE: To review the evidence regarding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in cats. DATABASES USED: PubMed, CAB abstracts. CONCLUSIONS: Nonsteroidal anti-inflammatory drugs should be used with caution in cats because of their low capacity for hepatic glucuronidation, which is the major mechanism of metabolism and excretion for this category of drugs. However, the evidence presented supports the short-term use of carprofen, flunixin, ketoprofen, meloxicam and tolfenamic acid as analgesics in cats. There were no data to support the safe chronic use of NSAIDs in cats.     

Testing the protective effectiveness of avirulent vaccines against trichophytosis in cattle

The protective action of live avirulent vaccine against bovine trichophytosis, produced by the Bioveta National Corporation at Ivanovice na Hané, was very good and fully comparable with the earlier vaccine produced from the virulent live culture of Trichophyton verrucosum. Experimental challenge with a massive dose of a virulent strain of T. verrucosum produced only minor surface dermal changes in the calves vaccinated with these vaccines, but these changes spontaneously disappeared in a short time. In the control non-vaccinated calves, large and deep lesions were induced by the challenge, spreading to the neighbouring tissues. Compared with both live biopreparations, the protective effect of inactivated vaccine prepared by the irradiation of virulent vaccine with Co60 was much lower.     

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.