Dexamethasone Sodium Phosphate and Phenyl Propionate; Prednisolone Acetate) on Blood Glucose, Leukocyte Values, and Milk Yield in Dairy Cows

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Dexamethasone Sodium Phosphate and Phenyl Propionate; Prednisolone Acetate) on Blood Glucose, Leukocyte Values, and Milk Yield in Dairy Cows PEER REVIEWED Magnitude and Duration of Effects of Two Corticosteroid Formulations (Dexamethasone Sodium Phosphate and Phenyl Propionate; Prednisolone Acetate) on Blood Glucose, Leukocyte Values, and Milk Yield in Dairy Cows 2 3 M.S. Lima1, DVM, PhD; G. Stilwell1, DVM, PhD; N. Carolino , MS, PhD; C.A. Hjerpe , DVM 1Faculdade de Medicina Veterinaria, CIISA, DC, Uniuersidade Tecnica de Lisboa, Portugal 2Unidade de Investiga<;iio de Recursos Geneticos, Reproduc;iio e Melhoramento Animal - INRB, Vale de Santarem, Santarem, Portugal 3School of Veterinary Medicine, University of California, Davis, Davis, CA 95616 Corresponding author: Dr. Miguel Lima, [email protected] Abstract Key words: dairy cows, glucocorticoids, dexametha­ sone, prednisolone The magnitude and duration of the effects of two corticosteroid formulations were determined on blood Resume glucose and leukocyte values and milk yield in nor­ mal, lactating dairy cows. One formulation contained L'ampleur et la duree des effets de deux formula­ a combination of dexamethasone sodium phosphate tions de corticosteroi:des sur la concentration sanguine and dexamethasone phenyl propionate (DEX). The de glucose et de leucocytes et sur la production de lait other contained prednisolone acetate (PRED). Blood ont ete examinees chez des vaches laitieres normales samples were obtained prior to and at 6, 24, 48, 72, en lactation. Une des formulations contenait une com­ 96, and 144 hours following administration of a single binaison de phosphate de sodium de dexamethasone et dose of DEX or PRED. Milk yield was determined for de dexamethasone phenylpropionique (DEX) alors que two days prior to drug administration and for seven l'autre contenait de !'acetate de prednisolone (PRED). days afterwards. Des echantillons sanguins ont ete obtenus avant et 6, Both corticosteroids caused significant increases in 24, 48, 72, 96 et 144 heures suivant !'administration blood glucose values, although DEX caused significantly d'une dose unique de DEX ou de PRED. La production larger and longer lasting increases. DEX also caused de lait a ete determinee sur une periode de deux jours significant leukocytosis and neutrophilia. PRED caused avant !'administration des drogues et sur une periode significant, very short lasting neutrophilia, but had no de sept jours par la suite. significant effect on total blood leukocyte values. Both Les deux corticostero1des ont cause une augmen­ drugs caused significant reductions in blood eosino­ tation de la concentration du glucose sanguin bien que phil and lymphocyte values, and significant increases le traitement DEX ait entraine une augmentation plus in monocyte values. DEX also caused a significant, forte et plus longue. Le traitement DEX a aussi cause marked drop in milk production on days 1, 2, and 6, une leucocytose et une neutrophilie significatives. Le post-administration. PRED did not significantly affect traitement PRED a cause une neutrophilie significative milk production. mais de tres courte duree et n'avait pas d'effet significatif Because DEX produced more dramatic and persis­ sur le nombre total de leucocytes sanguins. Les deux tent changes in blood glucose values and milk production drogues ont entraine des reductions significatives du than did PRED, the authors believe that DEX is likely nombre d'eosinophiles et de lymphocytes sanguins et une to be more efficacious than PRED for treating ketosis augmentation significative du nombre de monocytes. Le in dairy cows. Because DEX produced more dramatic traitement DEX a aussi cause une reduction significa­ and persistent effects on blood neutrophil values than tive marquee de la production laitiere aux jours 1, 2 et PRED, it is also likely to be a better option for use as 6 suivant !'administration. Le traitement PRED n'a pas an anti-inflammatory drug. affecte la production de lait. 60 THE BOVINE PRACTITIONER-VOL. 44, NO. 1 En raison des changements plus dramatiques et • Effects on the immune system: 1) immunosup­ persistants du traitement DEX par rapport au traite­ pression, and 2) alleviation of the clinical mani­ ment PRED sur la concentration sanguine du glucose et festations of certain immune-mediated diseases. sur la production de lait, les auteurs croient que le traite­ In order to establish a rational therapeutic regimen ment DEX est probablement plus efficace que le traite­ for a particular corticosteroid, it is important to consider ment PRED pour le traitement de l'acetonemie chez the duration and magnitude of the effects. A major ob­ les vaches laitieres. En raison des changements plus jective of this study was to investigate the duration of dramatiques et persistants du traitement DEX par rap­ the effects of two previously untested corticosteroids, port au traitement PRED sur le nombre de neutrophiles DEX and PRED, on milk production and on several sanguins, ce traitement est done probablement aussi blood parameters, as an indication of their metabolic une meilleure option comme drogue anti-inflammatoire. action (glucose) and anti-inflammatory activity (total leukocytes, neutrophils, eosinophils, monocytes, and Introduction lymphocytes). This study is the first report in which a combina­ Corticosteroids are among the most used and most tion of short-lasting and long-lasting glucocorticoids was misused drugs in veterinary medicine. Even so, scien­ administered to dairy cattle. It is also the first report of tifically verified information concerning corticosteroid administration of dexamethasone sodium phosphate and therapy is scarce for most species of domestic animals, dexamethasone phenyl propionate (DEX) and predniso­ especially regarding optimal dosages, treatment inter­ lone acetate (PRED) to cattle, and the effects on blood vals, efficacy, and side effects. Frequently, therapeutic glucose and leukocyte values and milk yield. recommendations for veterinary use of corticosteroids are based on uncontrolled clinical experiences of indi­ Materials and Methods vidual veterinary clinicians, or on information obtained from clinical trials in man or other species.6 The well­ Twelve normal Holstein cows were randomly documented euphoric effect of corticosteroids can be a selected from a herd of approximately 200 lactating valid reason for their use. 15 dairy cattle. All were between two and eight years of The clinical problems for which bovine practitio­ age, weighed between 1,210 and 1,595 lb (550 and 725 ners most often use corticosteroids include: 1) ketosis in kg; average weight 1,450 lb or 659 kg), were producing dairy cows, 2) calving paralysis (i.e., paralysis involving between 51 and 117 lb (23 and 53 kg) (average of 84 lb the sciatic, obturator or peroneal nerves), 3) aseptic or 38 kg) of milk per day, and had calved at least 65 laminitis, 4) localized post-surgical or post-traumatic days previously. inflammatory reactions, and 5) severe inflammation A single intramuscular injection of DEXa was ad­ associated with infectious processes. In these instances ministered to four cows at a dose of0.027 mg/lb (0.06 mg/ corticosteroids are used in combination with appropriate kg). DEX was a suspension in which each mL of water bactericidal antimicrobial drugs. 24 contained 1 mg of dexamethasone sodium phosphate 15 The range of effects of corticosteroids reported2•9• ,18 and 2 mg of dexamethasone phenyl propionate. Other in various species of animals include: chemicals included in each mL of DEX formulation were • Effects on carbohydrate, protein, and lipid me­ trisodium citrate (11.4 mg), benzilic alcohol (10.4 mg), tabolism: 1) increased protein catabolism and glu­ sodium chloride (4 mg), tragacantha (1 mg), methylcel­ coneogenesis, 2) decreased peripheral utilization lulose MH50 (0.4 mg), and dimethicone (0.08 mg). The of glucose (insulin antagonism), and 3) decreases label specified a dose of 10 mL for an adult dairy cow. We in lipid reserves. assumed that the average weight of such a cow would be • Anti-inflammatory effects: 1) increases in number 1100 lb (500 kg), and calculated that such a cow should of circulating neutrophils, 2) decreases in number receive 30 mg of combined drug, which is a dose of0.027 of circulating lymphocytes and eosinophils, and mg/lb (0.06 mg/kg). The label indicated that DEX had 3) reductions in localized inflammatory effects. both short (sodium phosphate) and long-acting (phenyl • Mineralocorticoid effects: 1) increased sodium, propionate) effects. chloride, and water retention, and 2) increased A single intramuscular injection of PREDh was potassium, phosphorus, and calcium excretion. administered to four different cows at a dose of0.18 mg/ •Reproductive effects: 1) induction of normal par­ lb (0.40 mg/kg). PRED was a suspension of prednisolone turition in late-term bovine pregnancies, and 2) acetate crystals in which each mL of water contained 10 induction of abortions in cattle, after the 180th mg of prednisolone acetate. Other chemicals included day of gestation, when used in combination with in each mL of PRED formulation were benzilic alcohol a prostaglandin. (9.45 mg), sodium chloride (9 mg), polysorbate 80 (4 SPRING 2010 61 mg), carboxymethylcellulose (3 mg), and dimethylpo­ Statistical Analysis lysiloxane antifoam (1 mg). The label specified a dose of 10 to 20 mL for an adult cow. We assumed that the Parameters measured in this study (blood glucose, weight of such a cow would be 1100 lb (500 kg), chose total leukocytes, neutrophils, eosinophils, monocytes, to use the 20 mL (200 mg) dose, and calculated that the lymphocytes, and milk production) were
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