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Topic:Anti-inflammatory
Anti-inflammatory agents are substances used to reduce inflammation in horses, often employed in the management of various equine conditions. These agents can be categorized into non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, among others. NSAIDs, such as phenylbutazone and flunixin meglumine, work by inhibiting cyclooxygenase enzymes, which play a role in the inflammatory process. Corticosteroids, like dexamethasone, modulate the immune response and reduce inflammation through their effects on gene expression. The use of anti-inflammatory agents is common in equine veterinary practice to alleviate pain and improve the quality of life in horses suffering from musculoskeletal disorders, colic, and other inflammatory conditions. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacology, efficacy, and safety of anti-inflammatory agents in equine medicine.
Effects of a phenylbutazone paste in ponies: model of acute nonimmune inflammation. In a 12-day treatment schedule, 5 ponies were given orally a paste formulation of phenylbutazone (PBZ) and 5 matched ponies were given equivalent doses of a placebo paste. On day 12, a mild, nonimmune inflammatory reaction was induced subcutaneously in the neck of each pony by inserting sterile, polyester sponge strips soaked in a 2% carrageenan solution. Exudate was collected at 4, 8, 12, and 24 hours by serial removal of sponges. There were no significant (P less than 0.05) differences in exudate protein concentration and leukocyte numbers between the treatment groups, but the group given PB...
Phenylbutazone and oxyphenbutazone distribution into tissue fluids in the horse. The clinically recommended dose rate of phenylbutazone (4.4 mg/kg) was administered intravenously as a single dose to five Welsh Mountain ponies. Distribution of phenylbutazone and its active metabolite oxyphenbutazone into body fluids was studied by measuring concentrations in plasma, tissue-cage fluid, peritoneal fluid and acute inflammatory exudate harvested from a polyester sponge model of inflammation. The ready penetration of phenylbutazone into inflammatory exudate was demonstrated by the relatively high mean value for Cmax of 12.4 micrograms/ml occurring at a time of 4.6 h and a mean A...
Effects of flunixin meglumine, phenylbutazone and a selective thromboxane synthetase inhibitor (UK-38,485) on thromboxane and prostacyclin production in healthy horses. The efficacy of three agents which alter the metabolism of arachidonic acid was investigated in normal, conscious horses. A dose response evaluation was made of flunixin meglumine and phenylbutazone, two cyclo-oxygenase inhibitors, and of a selective thromboxane synthetase inhibitor, UK-38,485. Radioimmunoassay of thromboxane B2 (TxB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) was used to assess the concentrations of thromboxane A2 (TxA2) and prostacyclin (PGI2) respectively, in serum. Flunixin was the most potent inhibitor of serum TxB2 and 6-keto PGF1 alpha production. UK-38,485 also de...
Phenylbutazone in the horse: a review. Phenylbutazone is an acidic, lipophilic, non-steroidal anti-inflammatory drug (NSAID). It is extensively metabolized in the horse. The metabolites so far identified, oxyphenbutazone, gamma-hydroxyoxyphenbutazone, account for some 25-30% of administered dose over 24 h. The plasma half-life of phenylbutazone and termination of its pharmacological action are determined primarily by its rate of hepatic metabolism. Phenylbutazone acts by inhibiting the cyclooxygenase enzyme system, which is responsible for synthesis of prostanoids such as PGE2. It appears to act on prostaglandin-H synthase and pros...
Renal toxicity of non-steroidal anti-inflammatory drugs. Non-steroidal anti-inflammatory drugs represent the most heavily prescribed and used class of drugs in human medicine. Most are derivatives of either salicylates, propionic acid, indoleacetic acid, anthranilic acid, pyrazolone, or oxicams. They depress the synthesis of prostaglandins from arachidonic acid by reversible inhibition of the enzyme cyclooxygenase. In the kidney, prostaglandins PGE2 and PGI2 modulate the vasoconstrictor effects of angiotensin II, norepinephrine, and vasopressin. In the presence of volume contraction, anesthesia, or disease states associated with high levels of these...
Failure of superoxide dismutase to alter equine arachidonic acid-induced platelet aggregation, in vitro or ex vivo. Superoxide dismutase (SOD), a free radical scavenger with anti-inflammatory activity, was administered IM to horses. Ex vivo platelet aggregation in response to arachidonic acid was monitored to determine whether exogenous SOD altered equine platelet prostaglandin metabolism. Preparations of platelet-rich plasma obtained before SOD administration were incubated with different concentrations of SOD and were aggregated with arachidonic acid. Superoxide dismutase did not exert a demonstrable effect, either ex vivo or in vitro. Aspirin abolished arachidonic acid-induced platelet aggregation in vit...
Sacroiliac lesions as a cause of chronic poor performance in competitive horses. The histories and clinical signs in 11 horses with longstanding poor performance attributed to chronic sacroiliac damage are described. The main clinical feature was a lack of impulsion from one or both hindlimbs causing a restriction in the hind gait or lowgrade lameness. A temporary improvement was often achieved using anti-inflammatory medication, but eventually all the horses were killed because of unsatisfactory progress at exercise. Post mortem examination revealed that changes were confined to the sacroiliac joints. The macroscopic and histological findings varied considerably and in on...
Clinical pharmacology and therapeutic uses of non-steroidal anti-inflammatory drugs in the horse. Weak organic acids possessing anti-inflammatory, analgesic and antipyretic properties--commonly known as aspirin-like drugs--have been used in equine medicine for almost 100 years. These non-steroidal anti-inflammatory drugs (NSAIDs) may be classified chemically into two groups; the enolic acids such as phenylbutazone and carboxylic acids like flunixin, meclofenamate and naproxen. All NSAIDs have similar and possibly identical modes of action accounting for both their therapeutic and their toxic effects. They block some part of the cyclo-oxygenase enzyme pathway and thereby suppress the synthe...
Effects of repeated endotoxin injections on prostanoids, hemodynamics, endothelial cells, and survival in ponies. The objectives of this study were to determine the pathophysiological effects of increasing amounts of endotoxin administered intraperitoneally (IP) for 24 hr at which time an intravenous (IV) injection of endotoxin was given. The ability of flunixin meglumine (FM), a nonsteroidal antiinflammatory drug with antiprostaglandin activity, to provide protective effects was also determined. Eight ponies were divided into two groups of four ponies each; one group (untreated) received endotoxin only and the other group (treated) received endotoxin while being treated with flunixin. Hemodynamic and ser...
Medical management of esophageal stricture in seven horses. Esophageal strictures developed in 7 horses that were treated for esophageal obstruction. A soft diet was fed to all horses, with intermittent nasogastric tube feeding in one, and medication included nonsteroidal anti-inflammatory drugs. Maximal reduction in esophageal lumen diameter was evident by 30 days following circumferential esophageal ulceration, after which lumen diameter increased rapidly. Five horses were clinically normal by 60 days after the esophageal injury. Two horses were euthanatized at the owner's request, 16 and 17 days after the original insult.
The acute inflammatory process, arachidonic acid metabolism and the mode of action of anti-inflammatory drugs. Arachidonic acid is a polyunsaturated fatty acid covalently bound in esterified form in the cell membranes of most body cells. Following irritation or injury, arachidonic acid is released and oxygenated by enzyme systems leading to the formation of an important group of inflammatory mediators, the eicosanoids. It is now recognised that eicosanoid release is fundamental to the inflammatory process. For example, the prostaglandins and other prostanoids, products of the cyclooxygenase enzyme pathway, have potent inflammatory properties and prostaglandin E2 is readily detectable in equine acute in...
Comparative effects of phenylbutazone, naproxen and flunixin meglumine on equine platelet aggregation and platelet factor 3 availability in vitro. Nonsteroidal anti-inflammatory drugs are commonly used in the treatment of inflammatory conditions, and have potential value in the treatment of thrombotic disease in the horse. This study compares the potency of three nonsteroidal anti-inflammatory drugs phenylbutazone, naproxen (equiproxen) and flunixin meglumine (banamine) with respect to their effects on equine platelets. Two functional responses of horse platelets were evaluated in vitro: their ability to aggregate and their ability to make available platelet factor 3 procoagulant activity. Flunixin at a concentration of 10(-6) M signific...
Review of 30 cases of peritonitis in the horse. Thirty cases of peritonitis, in which the diagnosis was based on a peritoneal fluid white blood cell count in excess of 10 x 10(9)/litre, are described. Colic, ileus, pyrexia, weight loss and diarrhoea were common presenting signs. Treatments included intravenous fluids, anti-inflammatory analgesics, broad spectrum antibiotics and anthelmintics. Duration of treatment was determined by the clinical condition of the horse and sequential analyses of the peritoneal fluid and the haemogram. In the majority of cases the primary cause of peritonitis was not accurately determined, but 21 horses (70 pe...
Equine immunology 3: immunopharmacology–anti-inflammatory and antihypersensitivity drugs. This article reviews anti-inflammatory and antihypersensitivity drugs under these 4 headings: Functional or physiological antagonists; Selective pharmacological inhibitors; Broad spectrum anti-inflammatory drugs; Miscellaneous inhibitors. The compounds considered include sympathomimetic amines, anticholinergic drugs, antihistamine drugs, tryptamine antagonists and dopamine antagonists, glucocorticosteroids and non-steroidal anti-inflammatory drugs, disodium cromoglycate and diethylcarbamazine citrate. The relationship of the pharmacological actions of these compounds is considered in the conte...
Factors affecting absorption of non-steroidal anti-inflammatory agents in the horse. The absorption of orally administered phenylbutazone (5 mg/kg) was studied in 10 thoroughbreds, eight ponies and four pony foals. Large variations in area under the curve (AUC) and peak plasma concentrations were found both within an animal and within groups of animals. Administration of phenylbutazone (5 mg/kg) following an overnight fast resulted in no difference among the three groups of animals with respect to AUC (0 to 24 hours), mean (+/- sd) values of which were 132 +/- 68, 107 +/- 48 and 98 +/- 6, respectively. Absorption characteristics of two oral phenylbutazone preparations (Equipal...
Dexamethasone metabolism in the horse. Dexamethasone and a metabolite, 9-fluoro-16α-methyl-6β, 11β, 16β-trihydroxy-1, 4-androstadiene-3, 17-dione, were detected in the urine of horses injected parenterally with the parent drug. The structure of the metabolite was elucidated by thin-layer chromatography, infrared spectroscopy, mass spectroscopy and nuclear magnetic resonance spectroscopy.
Current concepts in equine degenerative joint disease. Current concepts of pathogenesis, diagnosis, and treatment of equine degenerative joint disease are presented on the basis of recently acquired experimental and clinical knowledge. A number of concepts of pathogenesis need modification and the rationale of some of the newer treatments requires definition. Synovitis and other soft tissue changes are important components of the pathogenesis in addition to direct trauma to the articular cartilage. Loss of glycosaminoglycans constitutes an important biochemical "lesion" in the articular cartilage, making it weak and susceptible to trauma. Recognit...
Endotoxin-induced hemodynamic changes in ponies: effects of flunixin meglumine. A study was made of flunixin meglumine, an analgesic agent with antiinflammatory and antiprostaglandin activity, for the management of endotoxin-induced cardiovascular derangements. Three groups of 5 ponies each were used: controls--group 1; given endotoxin but not treated--group 2; and given endotoxin and treated with flunixin meglumine--group 3. Shock was induced in anesthetized ponies with IV injection of Escherichia coli endotoxin. Hemodynamic changes were monitored, and regional blood flow was determined at 4 different times, using microspheres labeled with 1 of 4 nuclides. There were ext...
Endotoxaemia in the horse. Endotoxins are non-protein fragments of the cell wall of Gram-negative bacteria. They must be absorbed into the circulation to produce disease and systemic effects are similar, regardless of bacterial source. Absorption of endotoxins occurs in obstructive bowel disease and may play a significant part in determining the severity of the disease. Many of the responses to experimentally administered endotoxin are identical to those of bowel diseases or the horse and include circulatory, haematological and metabolic alterations. Therapeutic approaches are indirect and include many drugs currently e...
