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Topic:Dexamethasone
Dexamethasone is a synthetic glucocorticoid commonly used in equine medicine for its anti-inflammatory and immunosuppressive properties. It is employed in the management of various inflammatory and allergic conditions in horses, such as arthritis, respiratory diseases, and skin disorders. Dexamethasone works by inhibiting the release of inflammatory mediators and suppressing immune responses. Its administration can be through oral, intravenous, or intramuscular routes, depending on the specific clinical situation. This page compiles peer-reviewed research studies and scholarly articles that investigate the pharmacokinetics, therapeutic applications, and potential side effects of dexamethasone in equine health.
Plasma histamine levels in laminitic horses and in horses treated with a corticosteroid. In seven sound horses histamine plasma levels were evaluated by means of a radioenzymatic method using the enzyme histamine-N-methyltransferase (mean = 4.46 nmol/l, SD = 1.55 nmol/l). Histamine levels of laminitic horses were significantly higher (n = 11; mean = 12.46 nmol/l, SD = 3.24 nmol/l). In three sound horses plasma histamine levels were determined over a two week period following a double administration of 10 mg dexamethasone-21-isonicotinate/100 kg body weight. Histamine levels remained within the range of sound control horses.
Relationships among LH, FSH and prolactin secretion, storage and response to secretagogue and hypothalamic GnRH content in ovariectomized pony mares administered testosterone, dihydrotestosterone, estradiol, progesterone, dexamethasone or follicular fluid. Thirty-five ovariectomized pony mares were used to study the relationships among luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) concentrations in blood (secretion), in pituitary (storage) and in blood after secretagogue administration, as well as the content of gonadotropin releasing hormone (GnRH) in hypothalamic areas, under various conditions of steroidal and nonsteroidal treatment. Five mares each were treated daily for 21 d with vegetable shortening (controls), testosterone (T; 150 micrograms/kg of body weight, BW), dihydrotestosterone (DHT; 150 microgram...
Triglyceride, insulin, and cortisol responses of ponies to fasting and dexamethasone administration. Ponies were evaluated for their response to feed withholding and exogenous administration of corticosteroids (dexamethasone 0.04 mg/kg intramuscular [IM]) in an attempt to reproduce the hyperlipemia syndrome. Because insulin resistance has been associated with hyperlipemia, all ponies were initially evaluated for insulin response to an oral glucose load and normal dexamethasone suppression of serum cortisol. Four ponies were identified as hyperinsulinemic reflecting insulin resistance. All ponies had suppressed cortisol concentrations following dexamethasone administration. Feed withdrawal res...
[Detection of dexamethasone in horses]. Due to their marked antiinflammatory effect, synthetic corticosteroids are used to mask illness, especially lameness in horses. The detection of these drugs in equine body fluids requires accurate methods, particularly where misuse of corticosteroids is suspected. Gas chromatography/mass spectrometry (GC/MS) is well established as a reliable technique for the identification of drugs in biological fluids. Using GC/MS, we determined dexamethasone levels in horse urine and serum after intravenous application of a therapeutic dose. Dexamethasone was detectable, in serum for up to six hours, and in...
Target animal safety test of a dexamethasone-prednisolone combination in horses. The target animal safety of a dexamethasone-prednisolone combination was studied on 12 horses divided into two groups of six each. One group of horses received the therapeutic dose of the combination (25 mg/animal dexamethasone pivalate and 75 mg/animal prednisolone) and the second group was given the threefold dose of it. The preparation was administered intravenously for 2 consecutive days. For assessment of safety a wide range of clinical, haematological, biochemical and urine variables were tested as laid down in the guidelines of the FDA. All horses treated by the therapeutic or the three...
Autoimmune haemolytic anaemia in eight horses. Autoimmune haemolytic anaemia was diagnosed in eight horses on the basis of a positive Coomb's test. The disease was considered to be idiopathic in three cases and secondary to another condition in five. The clinical signs included dullness and depression, pyrexia, jaundice and haemoglobinuria. In addition to anaemia, haematological evaluation commonly revealed auto-agglutination of red cells and anisocytosis; reticulocytosis and an increased mean corpuscular volume were less commonly observed. Four horses were successfully treated with dexamethasone, but the other four were destroyed or died ...
Action of dexamethasone in an equine model of acute non-immune inflammation. In a crossover study in seven New Forest ponies the actions of dexamethasone, at a dose rate of 0.06 mg kg-1 administered intravenously, were compared with those of a placebo treatment. Dexamethasone exerted expected effects on plasma and inflammatory exudate concentrations of cortisol and on blood glucose concentration and circulating leucocyte numbers, but it failed to affect exudate concentrations of the eicosanoids, prostaglandin E2, thromboxane B2, 6-keto-PGF1 alpha and leukotriene B4. These findings do not support the hypothesis that the anti-inflammatory actions of dexamethasone in the ...
[The effect of a single dose of dexamethasone on the production of superoxide anion and on the chemotaxis of blood polynuclear neutrophils in the horse]. Chemotaxis and superoxide anion production of neutrophils in healthy horses were investigated before and 8 h after, a single injection of dexamethasone at a dose of 0.045 mg/kg. Chemotaxis was studied by the technique of migration under agarose and superoxyde production was measured by ferricytochrome c reduction. Superoxide anion production was not changed, but the chemotactic index, with zymosan activated horse serum, was increased. The FMLP chemoattractant effect, at 10(-4) M, was slightly enhanced.
Gonadotropin secretion in ovariectomized pony mares treated with dexamethasone or progesterone and subsequently with dihydrotestosterone. Twelve long-term ovariectomized (OVX) pony mares were used to determine the effects of dexamethasone (DEX) or progesterone (PR) on concentrations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in daily blood samples and after administration of gonadotropin releasing hormone (GnRH). All mares were subsequently administered dihydrotestosterone (DHT) to determine if DEX or PR treatment altered the FSH or LH response to this androgen. Daily blood sampling was started on day 1. After a pretreatment injection of GnRH on day 5, four mares were administered DEX at 125 micrograms/kg...
Applications of equine models of acute inflammation. The Ciba-Geigy Prize for Research in Animal Health. The development of reproducible models of acute inflammation in which inflammatory heat is easily quantified and from which inflammatory exudate is readily harvested has facilitated studies in the horse of the actions of steroids and non-steroidal anti-inflammatory drugs (NSAIDS). Blockade of the synthesis of eicosanoids and suppression of inflammatory heat by clinical dose rates of NSAIDS suggests a causal link between the two events and provides further evidence for a role of these compounds in acute equine inflammation. The tendency for enolic and carboxylic acids NSAIDS to accumulate in in...
Complement-induced equine neutrophil adhesiveness and aggregation. Equine neutrophils (PMN) were isolated from citrated normal blood by density gradient separation on Ficoll-Hypaque to greater than 96% purity and 98% viability and an average of 3.78 x 10(7) PMN/ml. The agonist C5a des Arg was used in serial dilutions of whole zymosan-activated equine plasma (ZAP) or was partially purified from ZAP by column chromatography. Purified equine PMN exhibited rapid aggregation following incubation with C5a des Arg which was further dependent on the availability of divalent cations, especially Mg++. The microfilament disruptive agent cytochalasin B (5 micrograms/50 m...
Endotoxin-induced hemodynamic and prostaglandin changes in ponies: effects of flunixin meglumine, dexamethasone, and prednisolone. Shock was induced in four groups of anesthetized ponies with an intravenous injection of Escherichia coli endotoxin [125 micrograms/kg]. Five minutes after endotoxin injection, the ponies were given no treatment (group A), flunixin meglumine (FM:1.1 mg/kg) (group B), dexamethasone (2 mg/kg) (group C), or prednisolone (10 mg/kg) (group D). Additionally, FM was given every 3 hours, and the steroids were given at 3, 9, and 24 hours following endotoxin. Hemodynamic measurements were made during the 4-hour anesthetic period. Blood samples were collected for the analysis of prostaglandins, blood che...
The biotransformation and urinary excretion of dexamethasone in equine male castrates. The pro-drugs of dexamethasone, a potent glucocorticoid, are frequently used as anti-inflammatory steroids in equine veterinary practice. In the present study the biotransformation and urinary excretion of tritium labelled dexamethasone were investigated in cross-bred castrated male horses after therapeutic doses. Between 40-50% of the administered radioactivity was excreted in the urine within 24 h; a further 10% being excreted over the next 3 days. The urinary radioactivity was largely excreted in the unconjugated steroid fraction. In the first 24 h urine sample, 26-36% of the total dose was...
Quantitative methodology for corticosteroids based on chemical oxidation to electrophilic products for electron capture-negative chemical ionization using capillary gas chromatography-mass spectrometry. I. Assessment of feasibility in the analysis of horse urine for dexamethasone. Sensitive and specific methodology based on capillary column gas chromatography-electron capture-negative chemical ionization-mass spectrometry has been developed for the quantitative analysis of corticosteroids from biological fluids. The feasibility of this method is demonstrated in the quantitative analysis of dexamethasone in horse urine following administration of the drug. A structurally similar compound, 6 alpha-methylprednisolone, is added to the urine as an internal standard. The free dexamethasone and the internal standard are extracted and oxidized to high-electron-affinity 1,4-andr...
Effects of multiple intramuscular injections and doses of dexamethasone on plasma cortisol concentrations and adrenal responses to ACTH in horses. Adrenocortical function was assessed in horses given multiple IM doses of dexamethasone to determine the duration of adrenocortical suppression and insufficiency caused by 2 commonly used dosages of dexamethasone (0.044 and 0.088 mg/kg of body weight). Dexamethasone was administered at 5-day intervals for a total of 6 injections. Daily blood samples were collected. The plasma was frozen and later assayed for cortisol. An ACTH response test was determined 2 days before the first injection of dexamethasone and again 8 days after the last dexamethasone injection. Maximum suppression of plasma cor...
California serogroup virus infection in a horse with encephalitis. A 4-fold or greater seroconversion to the snowshoe hare serotype of the California serogroup of viruses in a horse with acute encephalitis was demonstrated by hemagglutination-inhibition, complement-fixation, and neutralization tests. The horse had a mild fever, was ataxic, had a head tilt, and was observed to circle. Chloramphenicol, dexamethasone, and B complex vitamins were administered and the horse recovered. The snowshoe hare virus is a recognized human pathogen, but it has not been associated with disease in horses. It is unknown whether horses play a role as amplification hosts for the...
Endotoxin-induced hematologic and blood chemical changes in ponies: effects of flunixin meglumine, dexamethasone, and prednisolone. To evaluate the effect of certain drugs on hematologic changes, blood chemical values, and survival in endotoxin shock, anesthetized ponies were given (IV) endotoxin (Escherichia coli O55:B5) and then treated as follows: Group A ponies--given a saline infusion at 5 minutes and at 3 hours after they were given endotoxin; group B ponies--given flunixin meglumine at 5 minutes and at 3, 6, 9, and 24 hours after they were given endotoxin; group C ponies--treated with dexamethasone; and group D ponies--treated with prednisolone at 5 minutes and at 3, 9, and 24 hours after they were given endotoxin. ...
Qualitative detection of corticosteroids in equine biological fluids and the comparison of relative dexamethasone metabolite/dexamethasone concentration in equine urine by micro-liquid chromatography-mass spectrometry. Several important corticosteroids were qualitatively determined in the plasma and urine of horses by micro-liquid chromatography-mass spectrometry (micro-LC-MS). The sensitivity and specificity of micro-LC-MS are demonstrated as is the ability of micro-LC-MS to deal with endogenous interferences. In turn, the relative amount of dexamethasone and its major unconjugated metabolite were determined in equine urine by micro-LC-MS; the conclusions drawn are reported.
Complications associated with the use of the cuffless endotracheal tube in the horse. Complications following the use of the cuffless large animal endotracheal tube during general anesthesia in 2 horses are reported. One horse developed laryngeal edema during recovery. The edema was treated successfully with dexamethasone, but severe laryngeal trauma was confirmed 24 hours later at necropsy. The second horse had a swollen tongue and had difficulty eating for 3 days after anesthesia. The condition resolved without treatment. this report is a reminder of the potential damage which can occur from endotracheal intubation.
Dexamethasone and prednisolone in the horse: pharmacokinetics and action on the adrenal gland. Pharmacokinetics of dexamethasone and prednisolone were studied in 6 horses given dexamethasone alcohol (IV or IM) or dexamethasone 21-isonicotinate as a solution IV or IM (50 micrograms/kg of body weight), prednisolone 21-sodium succinate IV or IM (0.6 mg/kg of body weight), or prednisolone acetate IM (0.6 mg/kg of body weight). Plasma concentrations were determined using a high-performance liquid chromatographic method. After dexamethasone alcohol (IV) or dexamethasone 21-isonicotinate (IV), the half-life of elimination was similar (53 minutes) for both formulations. After dexamethasone (alc...
[Aspergillus oryzae as a cause of keratomycosis in the horse]. A case of a spontaneous mycokeratitis of a previously injured cornea in a horse is described. The infection was caused by Aspergillus oryzae. After application of Chloramphenicol ophthalmic ointment a corneal clouding was found in the centre which was circularly sharply defined and which - after dispensing Dexamethason-Neomycin eye drops - expanded all over to a purulent keratitis. The demarcated and initially non purulent mycotic lesions largely improved after the application of tincture of iodine, whereas the purulent keratitis could be completely cured only by a lasting treatment with Lugol...
Morphologic and biochemical changes in cartilage of foals treated with dexamethasone. Epiphyseal and articular cartilages were examined in pony foals treated with intramuscular injections of either 0.5 mg dexamethasone per 100 kg bodyweight daily for 3, 8 or 11 months, or 5.0 mg per 100 kg for 11 months, and in horse foals treated with 5.0 mg per 100 kg for 20 weeks. The proximal femoral growth plates exhibited increased spatial separation between chondrocyte columns, narrowed zones of disorganized columnar and hypertrophic cartilage, abnormal penetration of hypertrophic cartilage by metaphyseal capillaries, retained cartilage in the spongiosa, distal terminal plate formation, ...
Sodium retention and cortisol (hydrocortisone) suppression caused by dexamethasone and triamcinolone in equids. Three ponies and 1 horse were bilaterally adrenalectomized (BADX). The initial hypoadrenal episode after BADX was reversed with 20 mg of dexamethasone (DXM) IM (n = 2) or 20 mg of triamcinolone (TMC) IM (n = 2). Nine hypoadrenal crises were reversed with 20 mg of DXM given IM (n = 4) or 20 mg of TMC given IM (n = 5). Sodium and chloride retention and potassium excretion were documented based on changes in serum electrolytes and urinary excretion. Eight intact adult horses were randomly assigned to 2 groups to study the effects of a single IM injection of DXM (0.044 mg/kg of body weight) or TMC...
The use of capillary column gas chromatography and negative ion chemical ionization mass spectrometry to confirm the administration of synthetic corticosteroids to horses. The negative ion chemical ionization mass spectra of the MO-TMS derivatives of the corticosteroids prednisolone, betamethasone and dexamethasone have been obtained using capillary column gas chromatography mass spectrometry. The spectra showed abundant diagnostic ions at m/z greater than 300 allowing for clear discrimination between the three steroid derivatives. A capillary column gas chromatographic mass spectrometric method using negative ion chemical ionization mass spectrometry has been developed to confirm the presence of the parent steroids in horse urine following the administration of...
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.
Effects of dexamethasone on endotoxin shock in the anesthetized pony: hematologic, blood gas, and coagulation changes. The effects of dexamethasone (1 mg/kg of body weight) on hematologic, blood gas, and blood coagulation values in anesthetized ponies during endotoxin-induced shock were evaluated. Fifteen ponies were assigned to 3 groups of 5 ponies each: group 1, anesthetized nontreated and dexamethasone-treated controls; group 2, endotoxin, nontreated; group 3, endotoxin, dexamethasone treated. The hematologic changes in this endotoxin shock model included leukopenia and hemoconcentration. Significant hematologic effects were not seen in ponies after administration of dexamethasone. However, dexamethasone tr...
Glucocorticoid suppression of oestrus, follicles, LH and ovulation in the mare. Dexamethasone, a synthetic glucocorticoid, was administered (30 mg/day) from Day 10 after ovulation to assess the involvement of the adrenal glands in the ovulatory cycle. Only 1 of 8 mares treated in this way exhibited behavioural oestrus, compared to 7 of 8 control mares. Mean maximum LH concentration and follicle size were significantly reduced. Ovulation occurred in 1 and possibly in 2 other treated mares, compared to all 8 control mares. The results demonstrated that dexamethasone can interfere with ovulation and associated events in the mare, but the mechanism of action is uncertain.
Calcium metabolism in glucocorticoid-treated pony foals. Pony foals were injected intramuscularly with 0, 0.5, or 5.0 mg dexamethasone per 100 kg body weight daily for up to 11 months. True absorption of dietary calcium was inhibited by treatment at 18 days (57% versus 14% of intake; P less than .01) and 10 months (72% versus 55% versus 43%: P less than .01), but not at 2 or 7 months, and was independent of age and treatment related decreases in intestinal calcium binding protein activities. Uninary excretion of calcium was increased by treatment through 7 months but decreased at 10 months. Treatment for 18 days resulted in total calcium excretions ...
Glucocorticoid-induced inhibition of osteolysis and the development of osteopetrosis, osteonecrosis and osteoporosis. Changes in the developing femoral epiphysis, especially those concerning the osteocytes, were examined in pony foals systemically treated with daily intramuscular injections of either 0.5 or 5.0 mg of dexamethasone per 100 kg bodyweight for either 3, 8 or 11 months. Midsagittal sections of proximal femur from animals treated for 3 months contained significantly more bone tissue subchondrally and epiphyseally than did sections from untreated ponies. Large portions of the bone tissue appeared necrotic, although osteoblasts and patent capillaries were abundant. After 8 months the bone sections re...
The use of combined high performance liquid chromatography negative ion chemical ionization mass spectrometry to confirm the administration of synthetic corticosteroids to horses. Negative ion chemical ionization mass spectra of some corticosteroids have been obtained by direct syringe introduction on to the Finnigan moving belt high-performance liquid chromatography-mass spectrometer interface. Proprietary preparations based upon dexamethasone, betamethasone and prednisolone were administered to horses at therapeutic dose level. Urine samples were extracted, the extracts purified by Sephadex LH-20 chromatography and the presence of the parent steroids in the eluates was confirmed by combined high-performance liquid chromatography negative ion chemical ionization mass s...
