Veterinary Toxicology and Pharmacology Commons^™

Gabapentin, A Human Therapeutic Medication And An Environmental Substance Transferring At Trace Levels To Horses: A Case Report., Kimberly Brewer, Jacob Machin, George Maylin, Clara Fenger, Abelardo Morales-Briceño, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Gabapentin, 1-(Aminomethyl)cyclohexaneacetic acid, MW 171.240, is a frequently prescribed high dose human medication that is also used recreationally. Gabapentin is orally absorbed; the dose can be 3,000 mg/day and it is excreted essentially unchanged in urine. Gabapentin is stable in the environment and routinely detected in urban wastewater. Gabapentin randomly transfers from humans to racing horses and is at times detected at pharmacologically ineffective / trace level concentrations in equine plasma and urine. In Ohio racing between January 2019 and July 2020,18 Gabapentin identifications, all less than 2 ng/ml in plasma, were reported. These identifications were ongoing because the horsemen …

Identifying Bisphosphonate Protein Biomarkers In Equine Sera Using Mass Spectrometry Methods, Malinda Jayne Alison Porter

Theses and Dissertations--Veterinary Science

Bone resorptive diseases affect humans and horses, alike. Examples of these diseases include osteoporosis, Paget’s disease, and osteogenesis imperfecta in humans, and navicular disease in the horse (Mitchell et al., 2019; Suva et al., 2021). Bisphosphonates are used to treat these diseases, and may remain in the bone for several years after administration, demonstrating the need for newer drug testing methods.

The purpose of the discovery phase of this study was to use blood samples of in-training horses which had been given an initial administration of the bisphosphonate tiludronate and identify protein biomarkers that changed in response to this class …

Science-Based Regulation Of Pharmacological Substances In Competition Horses, Jacob Machin

Theses and Dissertations--Toxicology and Cancer Biology

Current testing methodologies within equine forensic toxicology focus on arbitrary thresholds and zero-tolerance policy. Modern analytical chemistry’s limits of detection are low enough that oftentimes femtogram-per-milliliter amounts of a substance can readily be identified in both blood and urine of a horse. For most pharmacologically relevant compounds, these concentrations have no relevance to pharmacological effect. It is therefore crucial that testing methodologies to determine appropriate thresholds and cut-offs be developed that are driven by biological activity rather than arbitrary limits of detection. This dissertation looks to address this by suggesting a system of calculated Effective Plasma Concentrations by which a …

Kisspeptin Modulates Luteinizing Hormone Release And Ovarian Follicular Dynamics In Pre-Pubertal And Adult Murrah Buffaloes, Vishalkumar Pottapenjera, Srinivasa R. Rajanala, Chandrasekhar Reddy, Arunakumari Gangineni, Kiran Avula, Sandeep K. Bejjanki, Sriravali Sathagopam, Surabhi Kesharwani, Sathya Velmurugan

Pharmacology and Nutritional Sciences Faculty Publications

Kisspeptin is a neuropeptide that governs the reproductive axis upstream to GnRH. We wanted to study whether kisspeptin modulates plasma LH and FSH levels and ovarian follicular dynamics in buffaloes and whether kisspeptin can be used for fixed time artificial insemination (FTAI). We carried out these studies in comparison with buserelin, a potent GnRH agonist. Kisspeptin dose-dependently increased plasma LH levels. However, the kisspeptin-induced increase in LH was short-lived as the peak reached in 15–30 min returned to basal values by 1–2 h. The kisspeptin-induced increase in LH level was less compared to buserelin-induced increase in LH level which sustained …

Physiological Changes Associated With Pregnant Or Nonpregnant Mares Grazing Pastures Of Orchardgrass-Bluegrass, Kentucky 31 Tall Fescue Infected With Epichloë Coenophiala, Or Kyfa9821 Tall Fescue Infected With The Novel Endophyte Ar584, Victoria A. Taylor

Theses and Dissertations--Veterinary Science

Kentucky 31 tall fescue (KY31) infected with the common toxic endophyte strains of Epichloё coenophiala produces toxic alkaloids that improve plant vigor, but cause numerous adverse effects in grazing animals. Researchers developed a variety of KY31 containing an alternative strain of E. coenophiala, termed novel endophyte (NE). Adverse health effects in mares have not been evaluated.

Experiments in this thesis tested the hypothesis that the NE pasture does not cause adverse effects typically associated with KY31. Specific aims were to: 1) compare forage ergovaline concentrations between KY31 vs NE pastures; 2) evaluate palmar artery diameters in mares grazing KY31, …

Reversible Downregulation Of Hypothalamic-Pituitary-Gonadal Axis In The Stallion With A Third-Generation Gnrh Antagonist, Gabriel Monteiro Davolli

Theses and Dissertations--Veterinary Science

The objectives of this thesis were: (1) to evaluate the downregulation of the stallion hypothalamic-pituitary-gonadal (HPG) axis by a GnRH antagonist (acyline) based upon endocrine, seminal, testicular and behavioral effects, and (2) to assess recovery after treatment. Stallions were treated for 50 days (n=4; 330µg/kg acyline q 5d) and controls (n=4) received vehicle alone. Stallions were assessed pre-treatment and for 72 days after last treatment. Treatment induced declines (p<0.05) in FSH, LH, testosterone (to castrate levels) and estrone sulfate. Gonadotropins and testosterone returned to control values within nine days and estrone sulfate by 14 days after treatment discontinuation. Acyline-treated stallions failed to respond with FSH, LH and testosterone increase after exogenous GnRH stimulation (25µg gonadorelin, IV) compared to pre-treatment and control stimulation. Total sperm numbers and motility were reduced in acyline-treated stallions, as well as total seminal plasma protein and testicular volume (p<0.05). Time to ejaculation was increased in acyline group (p<0.5). Testicular, sexual behavior and most seminal parameters regained normal levels within 72 days after treatment ceased. Sperm output of acyline-treated stallions was regained within seven months after ending treatment. Acyline reversibly suppressed the stallion HPG axis, thus has potential for treating the androgen-dependent Equine-Arteritis-Virus carrier state and as behavior modulator.

Glucocorticoid-Induced Chondrocyte Cytotoxicity At Doses Recommended For Intra-Articular Therapy In Horses, Wenying Zhu

Theses and Dissertations--Veterinary Science

Intra-articular glucocorticoid injections are commonly used to treat synovitis and osteoarthritis in horses. These agents are highly effective at relieving pain, swelling, and other symptoms of joint inflammation. The drugs also have therapeutic benefits by down regulating the expression of cytokines and protease enzymes that participate in the degradation of articular cartilage. However, detrimental effects on chondrocyte function and cell viability that is independent of osteoarthritis pathogenesis have been described and linked to glucocorticoid use. These side effects are both drug- and dose-dependent. This study tested the hypothesis that manufacture recommended dosage levels of methylprednisolone, betamethasone, and triamcinolone that are …

Current Therapeutic Approaches To Equine Protozoal Myeloencephalitis, L. Dirikolu, Jonathan H. Foreman, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Equine protozoal myeloencephalitis is the most important infectious neurologic disease of horses in the Western Hemisphere. Equine protozoal myeloencephalitis can interfere with a horse's ability to race, work, and perform; untreated, EPM can be lethal. Antemortem diagnosis of EPM is challenging, requiring careful evaluation of the animal's history, clinical signs, and laboratory data, with rigorous exclusion of other causes.

Therapeutic approaches to EPM are evolving. First-generation therapeutic approaches for EPM were based on the classic anti–Toxoplasma gondii pyrimethamine–sulfonamide combinations; treatment is prolonged and can be associated with a considerable relapse rate, which may be associated with the difficulty in …

A Toxicology And Clinical Study Of Post Race Epitaxis Associated With Exercise Induced Pulmonary Hemorrhage In Thoroughbred Race Horses At The Racecourse Rinconada, Caracas, Venezuela, Abelardo Morales Briceno, Diana Villoria Leon, Kimberly Brewer, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

The aim of this study was to describe cases of epistaxis associated with post-race Exercise Induced Pulmonary Hemorrhage (EIPH) in Thoroughbred horses at the Hippodrome "La Rinconada", Caracas, Venezuela, through a clinic pathological study. We studied a total of 29 cases of epistaxis post-race in Thoroughbred horses at the Hippodrome La Rinconada, Caracas, Venezuela, which is 2,950 meters above sea level. The study included horses between the ages of 2-5 years, 16 stallions and 13 mares, weighing between 450-510 kg. They underwent a clinical examination, although horses presenting with epistaxis were in an emergency situation. Samples of blood and urine …

Absence Of Detectable Pharmacological Effects After Oral Administration Of Isoxsuprine, J. Daniel Harkins, G. D. Mundy, S. Stanley, W. E. Woods, R. A. Sams, D. R. Richardson, S. C. Grambow, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Isoxsuprine is reported to be a peripheral vasodilator used in human and veterinary medicine to treat ischaemic vascular disease. In horses, it is generally administered orally to treat navicular disease and other lower limb problems. To deflne the scope and duration of its pharmacological responses after oral administration, 6 horses were dosed with isoxsuprine HCI (1.2 mg/kg bwt) q. 12 h for 8 days and then tested to assess the duration and extent of pharmacological actions. There was no significant difference between isoxsuprine and control treatment values for heart rate, spontaneous activity, sweat production, anal muscle tone, core and skin …

An Overview Of The Methylxanthines And Their Regulation In The Horse, J Daniel Harkins, W. Allen Rees, G. D. Mundy, Scott D. Stanley, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Caffiene, theophylline and theobromine are naturally occurring members of the methylxanthine family;pentoxfylline, dyphylline and enprofylline are structurally related synthetic pharmaceuticals. Caffiene has predominantly central nervous system effects, theophylline, dyphylline and enprofylline have predominantly bronchodilator effects, while theobromine is associated with diuretic responses. Pentoxfylline is thought to increase red cell deformability and facillitate blood flow through capillary beds. The methylxanthines are not highly potent agents; they are typically administered in gram doses and they tend to have relatively long half-lives. They remain detectable in plasma and urine for relatively long periods. Similarly, traces of the naturally occurring members of this family …

The Pharmacologic Effects Of Isoxsuprine, J. Daniel Harkins, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Isoxsuprine is a therapeutic medication used to treat navicular disease and other lower limb problems in horses and is one of the more frequently detected therapeutic agents in racing horses. In crossover studies, horses were administered intravenous and oral isoxsuprine to determine the character and duration of pharmacological effects. Following intravenous administration, isoxsuprine significantly increased heart rate, spontaneous activity, and sweat production. There was an apparent, although statistically insignificant, increase in cutaneous blood flow. Skin temperature decreased below control values, and there was a significant decrease in core temperature. Isoxsuprine also reduced smooth muscle tone. In contrast, after oral dosing, …

Hordenine : Pharmacology, Pharmacokinetics And Behavioural Effects In The Horse, M. Frank, T. J. Weckman, T. Wood, W. E. Woods, Chen L. Tai, Shih-Ling Chang, A. Ewing, J. W. Blake, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Hordenine is an alkaloid occurring naturally in grains, sprouting barley, and certain grasses. It is occasionally found in post race urine samples, and therefore we investigated its pharmacological actions in the horse. Hordenine (2.0 mgkg bodyweight [bwt]) was administered by rapid intravenous (iv) injection to 10 horses. Typically, dosed horses showed a tlehmen response and defecated within 60 secs. All horses showed substantial respiratory distress. Respiratory rates increased about 250 per cent and heart rates were approximately double that of resting values. All animals broke out in a sweat shortly after iv injection, but basal body temperature was not affected. …

Phenylbutazone In The Horse: A Review, Thomas Tobin, S. Chay, S. Kamerling, W. E. Woods, T. J. Weckman, J. W. Blake, P. Lees

Maxwell H. Gluck Equine Research Center Faculty Publications

Phenylbutazone is an acidic, lipophilic, nonsteroidal anti-inflammatory drug (NSAID). It is extensively metabolized in the horse. The metabolites so far identified, oxyphenbutazone, y-hydroxyphenylbutazone and y-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 PGE?. It appears to act on prostaglalidin-H synthase and prostacyclin synthase, after conversion by prostaglandin-H synthase to reactive intermediates. It markedly reduces prostanoid-dependent swelling, edema, erythema, and hypersensitivity …

Pharmacokinetics And Protein Binding Of Morphine In Horses, Joan Combie, Thomas E. Nugent, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Morphine could be detected in horses dosed with 0.1 mg of drug/kg of body weight for up to 48 hours in blood and 144 hours in urine. This dose of morphine elicited no observ­able effects and is a suggested an­algesic dose. Computer analysis revealed that a 3-compartment open system was the best fitting model with a serum half life of 87.9 minutes and a urine half life of 101.1 minutes. Binding to equine serum proteins was linear over a drug con­centration range of 3.88 x 10-5M to 3.50 x 10-aM and averaged 31.6%. In RBC-partitioning experiments, 78.1 % of the …

Drugs And The Performance Horse, Thomas Tobin

Veterinary Science Books

This book presents an unprecedented account of the actions, effects and consequences of drug use in performance horses. Written for horsemen by a veterinarian and world authority on equine drugs, it deals with all classes, types, and uses of drugs. Professor Tobin describes how the drugs act, how they influence performance, and the problems they may cause. He explains the drug testing process and presents the best information available on the clearance times for drugs in horses. The text is written in plain language and with a touch of humor.