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Topic:Pharmacodynamics

Pharmacodynamics in horses refers to the study of how drugs affect the equine body, encompassing the mechanisms of action, the relationship between drug concentration and effect, and the duration of these effects. This field examines how drugs interact with biological systems in horses to produce therapeutic or adverse effects. Key aspects include receptor binding, post-receptor effects, and chemical interactions. Understanding pharmacodynamics is essential for determining appropriate dosages, predicting drug interactions, and assessing therapeutic outcomes in equine medicine. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacodynamic properties of various drugs in horses, focusing on their effects, efficacy, and safety profiles.
Pharmacokinetics, penetration into cerebrospinal fluid, and hematologic effects after multiple oral administrations of pyrimethamine to horses.
American journal of veterinary research    December 1, 1992   Volume 53, Issue 12 2296-2299 
Clarke CR, MacAllister CG, Burrows GE, Ewing P, Spillers DK, Burrows SL.Pharmacokinetics, CSF penetration, and hematologic effects of oral administration of pyrimethamine were studied after multiple dosing. Pyrimethamine (1 mg/kg of body weight) was administered orally once a day for 10 days to 5 adult horses, and blood samples were collected frequently after the first, fifth, and tenth doses. The CSF samples were obtained by cisternal puncture 4 to 6 hours after administration of the first, third, seventh, and tenth doses. Pyrimethamine concentration in plasma and CSF was quantified by gas chromatography, and plasma concentration-time data were analyzed, using a ...
Temporal effects of inhaled histamine and methacholine aerosols on the pulmonary mechanics of thoroughbred horses.
Journal of veterinary pharmacology and therapeutics    December 1, 1992   Volume 15, Issue 4 317-331 doi: 10.1111/j.1365-2885.1992.tb01024.x
Guthrie AJ, Beadle RE, Bateman RD, White CE.This paper presents a method for on-line determination of pulmonary mechanics in standing, non-sedated horses during and following inhalation of aerosolized drug solutions. This method was used to evaluate the temporal effects of inhaled histamine and methacholine aerosols on pulmonary mechanics in 18 Thoroughbred horses. The following were concluded from this study. The extremely large between-breath variation, for all variables used to evaluate pulmonary mechanics in the horse, limits the usefulness of these variables for modeling the non-specific pulmonary responses to inhaled stimulants on...
Pharmacokinetics of ceftiofur sodium in neonatal foals after intramuscular injection.
Equine veterinary journal    November 1, 1992   Volume 24, Issue 6 485-486 doi: 10.1111/j.2042-3306.1992.tb02883.x
Meyer JC, Brown MP, Gronwall RR, Merritt K.No abstract available
Effects of furosemide and pentoxifylline on blood flow properties in horses.
American journal of veterinary research    November 1, 1992   Volume 53, Issue 11 2043-2049 
Geor RJ, Weiss DJ, Burris SM, Smith CM.The effects of furosemide and pentoxifylline on blood flow properties in horses were investigated. Hematologic and rheologic changes were examined in 4 horses before and 3 minutes after administration of epinephrine (1 mg, IV). The next day, hemorheologic changes were determined before and 3 hours after administration of furosemide (1 mg/kg of body weight, IM), and after administration of epinephrine at the sampling at 3 hours. Hematologic and rheologic changes were evaluated weekly in 3 horses given pentoxifylline (8.5 mg/kg, q 12 h, PO) for 28 days. In addition, hemorheologic responses to ep...
Additive and synergistic pharmacologic inhibition of equine fibrinoligase (factor XIIIa*-like) biochemical activity.
American journal of veterinary research    November 1, 1992   Volume 53, Issue 11 2058-2066 
Coyne CP, Smith JE, Keeton K.A selected group of pharmaceutical compounds were evaluated for the ability to inhibit the biochemical activity of fibrinoligase (coagulation factor XIIIa*) in pooled equine plasma. Criteria for the pharmaceuticals selected were based on the mechanism of the transglutamination biochemical reaction mediated by coagulation factor XIIa*. These criteria were complemented by recognition of the molecular configuration and chemical composition of amino acid residue side chains involved in the process of covalent fibrin monomer polymerization (cross-linking, transglutamination) mediated by this enzyme...
Effects of xylazine on airway function in ponies with recurrent airway obstruction.
American journal of veterinary research    October 1, 1992   Volume 53, Issue 10 1813-1817 
Broadstone RV, Gray PR, Robinson NE, Derksen FJ.The effect of IV administration of the alpha 2-adrenoceptor agonist xylazine hydrochloride (0.5 mg/kg of body weight) was examined in ponies with recurrent obstructive pulmonary disease, commonly called heaves. Six ponies with the disease (principals) were studied during clinical remission and during an acute attack of airway obstruction precipitated by stabling and feeding of dusty hay. Six control ponies were also studied. In principal ponies with airway obstruction, xylazine administration significantly (P < 0.05) decreased pulmonary resistance and increased dynamic compliance, but did n...
Effects of pentoxifylline on equine neutrophil function and flow properties.
Canadian journal of veterinary research = Revue canadienne de recherche veterinaire    October 1, 1992   Volume 56, Issue 4 313-317 
Weiss DJ, Geor RJ, Burris SM, Smith CM.Pentoxifylline has been reported to improve peripheral vascular circulation by altering the flow properties of blood. To determine if the hemorrheological effects of pentoxifylline were mediated by alterations in neutrophil function and/or flow properties, we evaluated the drug's effects on equine neutrophils in vitro. Pentoxifylline, at a concentration of 1 x 10(-1) M, but not at concentrations of 1 x 10(-6) M to 1 x 10(-2) M, markedly suppressed neutrophil superoxide production, zymosan phagocytosis and adherence to nylon wool. Pentoxifylline failed to improve neutrophil filterability throug...
Effect of the somatostatin analogue octreotide on gastric fluid pH in ponies.
American journal of veterinary research    October 1, 1992   Volume 53, Issue 10 1818-1821 
Sojka JE, Weiss JS, Samuels ML, You GM.The effect of the somatostatin analogue, octreotide, on gastric fluid pH was investigated in 4 ponies. Gastric fluid pH was determined after SC administration of octreotide or physiologic saline solution (control). A baseline sample of fluid was obtained, the agent was given, and 8 additional samples were collected hourly. Administration of octreotide at all dosages tested (0.1, 0.5, 1.0, and 5.0 micrograms/kg of body weight) increased gastric pH to > 5.0. Baseline values were consistently 4.0 for 2.4 +/- 1.2, 4.8 +/- 0.8, 5.7 +/- 1.3, and 5.4 +/- 2.6 (mean +/- SD) continuous hours, respec...
Respiratory mucociliary clearance in the horse in health and disease, and its pharmaceutical modification.
The Veterinary record    September 12, 1992   Volume 131, Issue 11 229-235 doi: 10.1136/vr.131.11.229
Dixon PM.The structure and possible functions of respiratory secretions are reviewed. In the equine, goblet (mucus producing) cells are the main source but little information is available on the volume or composition of equine respiratory secretions. Airway mucus has complex and incompletely understood physical characteristics which can be partially assessed by a wide range of in vitro and biological techniques. The complex relationship between mucus structure and its propulsion by the airway cilia are discussed, both in health and with pulmonary disease. Mucokinesis in the horse has been assessed visu...
Pharmacokinetics of gentamicin and antipyrine in the horse–effect of advancing age.
Journal of veterinary pharmacology and therapeutics    September 1, 1992   Volume 15, Issue 3 309-313 doi: 10.1111/j.1365-2885.1992.tb01022.x
Clarke CR, Lochner FK, Bellamy J.No abstract available
Synovial and serum levels of triamcinolone following intra-articular administration of triamcinolone acetonide in the horse.
Journal of veterinary pharmacology and therapeutics    September 1, 1992   Volume 15, Issue 3 240-246 doi: 10.1111/j.1365-2885.1992.tb01012.x
Chen CL, Sailor JA, Collier J, Wiegand J.Seven mature thoroughbred horses, weighing between 400 and 541 kg, were each injected intra-articularly into three joints with 6 mg/joint of triamcinolone acetonide (Vetalog). The fourth joint, the control, was injected with saline. Synovial fluid was taken from all four legs of the horses on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following the injections. Triamcinolone acetonide was assayed by a radioimmunoassay. Blood was collected at 1, 2, 4, 6, 12 h and on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following injection of either triamcinolone or saline. Both cortisol and triamcinolone were as...
Effect of a histamine H2 type receptor antagonist (WY 45, 727) on the healing of gastric ulcers in ponies.
Journal of veterinary internal medicine    September 1, 1992   Volume 6, Issue 5 271-275 doi: 10.1111/j.1939-1676.1992.tb00351.x
MacAllister CG, Sangiah S, Mauromoustakos A.Using video gastroscopy, the efficacy of a Histamine-H2 type receptor antagonist (WY 45, 727) was investigated in young ponies with spontaneous and experimentally induced gastric ulcers. Oral administration of WY 45, 727 at 2 mg/kg and 10 mg/kg of body weight every 12 hours for 14 days resulted in complete healing of spontaneous gastric ulcers in the non-glandular portion of the stomach in 2/5 (40%) and 3/4 (75%) of the ponies, respectively, compared (P < 0.05) to 0/5 (0%) placebo-treated ponies. After intramuscular administration of flunixin meglumine at 1.5 mg/kg body weight every 8 hours fo...
Effect of probenecid on disposition kinetics of ampicillin in horses.
The Veterinary record    August 22, 1992   Volume 131, Issue 8 173-175 doi: 10.1136/vr.131.8.173
Sarasola P, McKellar QA.The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present...
Parasympathetic influence on the arrhythmogenicity of graded dobutamine infusions in halothane-anesthetized horses.
American journal of veterinary research    July 1, 1992   Volume 53, Issue 7 1154-1160 
Light GS, Hellyer PW, Swanson CR.We investigated the influence of parasympathetic tone on the arrhythmogenicity of graded dobutamine infusions in horses anesthetized under clinical conditions. Six horses were used in 9 trials. Two consecutive series of graded dobutamine infusions were given IV; each continuous graded dobutamine infusion was administered for 20 minutes. The dobutamine infusion dosage (5, 10, 15, and 20 micrograms/kg of body weight/min) was increased at 5-minute intervals. Isovolumetric saline solution vehicle (v) or atropine (A; 0.04 mg/kg) was administered IV, or bilateral vagotomy (VG) was performed as a tre...
Regional perfusion of the equine carpus for antibiotic delivery.
Veterinary surgery : VS    July 1, 1992   Volume 21, Issue 4 279-285 doi: 10.1111/j.1532-950x.1992.tb00064.x
Whitehair KJ, Blevins WE, Fessler JF, Van Sickle DC, White MR, Bill RP.Regional perfusion of carpal tissues by forced intramedullary administration of fluids was evaluated in 10 horses. Results of subtraction radiography after perfusion with a contrast medium demonstrated that perfusate was delivered to the carpal tissues by the venous system. Perfused India ink was distributed uniformly in the antebrachiocarpal and middle carpal synovial membranes. Histologically, the ink was within the venules of the synovial villi. Immediately after perfusion with gentamicin sulfate (1 g), the gentamicin concentrations in the synovial fluid and synovial membrane of the antebra...
Bioavailability and bioequivalence of veterinary drug dosage forms, with particular reference to horses: an overview.
Journal of veterinary pharmacology and therapeutics    June 1, 1992   Volume 15, Issue 2 160-173 doi: 10.1111/j.1365-2885.1992.tb01003.x
Baggot JD.The route of administration and formulation of the dosage form affect the bioavailability (rate and extent of absorption) of a drug and may thereby influence the intensity and duration of the pharmacological effect. Location of injection site may affect the plasma concentration profile of drugs administered as aqueous suspensions or sustained release parenteral preparations (procaine penicillin G). When absorption influences the rate of elimination ('flip-flop' phenomenon), the apparent half-life of the drug will be increased (cefazolin sodium, i.m.; meclofenamic acid, p.o.). Absorption genera...
Pharmacokinetics of cephradine in neonatal foals after single oral dosing.
Equine veterinary journal    May 1, 1992   Volume 24, Issue 3 242-243 doi: 10.1111/j.2042-3306.1992.tb02823.x
Henry MM, Morris DD, Lakritz J, Aucoin D.No abstract available
Effect of changes in urine pH on plasma pharmacokinetic variables of ampicillin sodium in horses.
American journal of veterinary research    May 1, 1992   Volume 53, Issue 5 711-715 
Sarasola P, Horspool LJ, McKellar QA.The effect of urine pH on plasma disposition of ampicillin sodium was evaluated. A single dose of 10 mg/kg of body weight was administered IV to Thoroughbreds with alkaline (pH greater than 8.0) or acidic (pH less than 4.5) urine. Urine alkalinity was achieved and maintained by oral administration of up to 400 mg of sodium bicarbonate/kg/d, and acidity was achieved and maintained by oral administration of up to 400 mg of ammonium chloride/kg/d. Ampicillin sodium was measured in the plasma of horses by use of an agar diffusion microbiological assay with Bacillus subtilis as the test organism. T...
Relation between pharmacokinetics of amikacin sulfate and sepsis score in clinically normal and hospitalized neonatal foals.
Journal of the American Veterinary Medical Association    May 1, 1992   Volume 200, Issue 9 1339-1343 
Wichtel MG, Breuhaus BA, Aucoin D.Pharmacokinetic values after IV administration of amikacin sulfate were determined for clinically normal and hospitalized foals during the first week of life. The relations between drug disposition and sepsis score and serum creatinine concentration also were studied. In clinically normal foals, differences in sepsis score, serum creatinine concentration, and pharmacokinetic variables of amikacin were not found between foals 1 to 3 and 4 to 7 days old. In hospitalized foals, sepsis score, serum creatinine concentration, area under the curve, area under the moment curve, and mean residence time...
Effects of WEB 2086, an antagonist to the receptor for platelet-activating factor (PAF), on PAF-induced responses in the horse.
Equine veterinary journal    May 1, 1992   Volume 24, Issue 3 203-207 doi: 10.1111/j.2042-3306.1992.tb02815.x
Foster AP, Lees P, Andrews MJ, Cunningham FM.Platelet-activating factor (PAF) causes oedema and neutrophil accumulation when injected into the skin of normal horses. PAF is also known to induce aggregation of horse platelets in vitro. The selective PAF receptor antagonist WEB 2086 has now been used to determine whether these effects are mediated by PAF receptor activation. Addition of WEB 2086 to equine platelets in vitro inhibited PAF-induced aggregation in a competitive reversible manner (pA2 = 7.14). Inhibition of in vivo inflammatory responses to PAF occurred after local administration of WEB 2086: wheal formation induced by 0.1 micr...
Determination of sensitivity to metocurine in exercised horses.
American journal of veterinary research    May 1, 1992   Volume 53, Issue 5 757-761 
White DA, Hildebrand SV, Jones JH, Fung DL, Gronert GA.On the basis of results in dogs, conditioning exercise may increase sensitivity to nondepolarizing muscle relaxants. Five Thoroughbreds were exercised/conditioned 3 times weekly on a treadmill for 8 months. Increasing maximal rate of O2 consumption verified that the horses were responding to exercise conditioning. Six nonexercised Thoroughbreds served as the control group. Studies were done with horses under general anesthesia by use of halothane during partial paralysis by a brief constant-rate infusion with the muscle relaxant, metocurine iodide. Quantification of degree of paralysis of the ...
Clinical pharmacokinetics in veterinary medicine.
Clinical pharmacokinetics    April 1, 1992   Volume 22, Issue 4 254-273 doi: 10.2165/00003088-199222040-00002
Baggot JD.Veterinary and human pharmacology differ principally in the range of species in which drugs are used and studied. In animals, as in humans, an understanding of the dose-effect relationship can be obtained by linking pharmacokinetic behaviour with pharmacodynamic information. Studies of different classes of drugs support the assumption that the range of therapeutic plasma concentrations in animals is generally the same as in humans. The requirement for species differences in dosage or administration rate (dose/dosage interval) may be attributed to variations in pharmacokinetic behaviour or phar...
Effect of probenecid on the pharmacokinetics of flunixin meglumine and phenylbutazone in healthy mares.
American journal of veterinary research    March 1, 1992   Volume 53, Issue 3 372-374 
Zertuche JM, Brown MP, Gronwall R, Merritt K.Pharmacokinetic values for flunixin meglumine (1 mg/kg of body weight) and phenylbutazone (4 mg/kg) dosages were determined after a single IV injection with and without concurrent intragastric administration of probenecid (50 mg/kg) in 6 healthy mares. Significant difference was not apparent in the pharmacokinetic values of flunixin meglumine with and without concurrent probenecid administration. Significant (P less than or equal to 0.05) increase was evident in the 12-hour mean concentration of phenylbutazone (11.45 +/- 1.66 micrograms/ml without probenecid; 14.56 +/- 1.20 micrograms/ml with ...
Plasma elimination and urinary excretion of procaine after administration of different products to standardbred mares.
Equine veterinary journal    March 1, 1992   Volume 24, Issue 2 118-124 doi: 10.1111/j.2042-3306.1992.tb02795.x
Stevenson AJ, Weber MP, Todi F, Young L, Beaumier P, Kacew S.Plasma and urinary concentrations of procaine were examined in Standardbred mares after subcutaneous administration of various doses (80 mg to 1600 mg) of procaine hydrochloride. Regardless of dose, peak plasma procaine values occurred within 1 h, but remained detectable in a dose-dependent manner, with procaine present at 1 h with the 80 mg dose and 6 h at the 1600 mg dose. Similarly, peak urinary procaine concentrations were attained within 1.5 to 3 h, irrespective of dose, while detection time was dose-dependent, being 23 h for 80-200 mg doses but as long as 30-54 h with the 1600 mg dose. W...
Pharmacokinetics of tolfenamic acid in the horse.
Equine veterinary journal. Supplement    February 1, 1992   Issue 11 69-72 doi: 10.1111/j.2042-3306.1992.tb04778.x
Jaussaud P, Guieu D, Bellon C, Barbier B, Lhopital MC, Sechet R, Courtot D, Toutain PL.The pharmacokinetics of tolfenamic acid were studied in five ponies after an intravenous (iv) administration (2 mg/kg bodyweight [bwt]) and in four horses after an oral administration (30 mg/kg bwt) of tolfenamic acid. The plasma levels were determined by high pressure liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). For the iv administration, a three-compartment model was used to represent the plasma concentration-time curve of the drug. The elimination half-life of the compound was 6.1 +/- 1.5 h, the total body clearance was 72.4 +/- 16.7 ml/kg bwt/h and the ste...
The effects of famotidine, ranitidine and magnesium hydroxide/aluminium hydroxide on gastric fluid pH in adult horses.
Equine veterinary journal. Supplement    February 1, 1992   Issue 11 52-55 doi: 10.1111/j.2042-3306.1992.tb04773.x
Murray MJ, Grodinsky C.Gastric fluid pH was measured in five adult horses following nasogastric administration of famotidine, 0.5, 1.0, and 2.0 mg/kg bodyweight (bwt); ranitidine, 4.4 and 6.6 mg/kg bwt and an antacid containing magnesium hydroxide (40 mg/ml) and aluminium hydroxide (45 mg/ml), 120 and 180 ml. Fluid was aspirated through a 16 French nasogastric feeding tube at 15 min intervals, and pH was measured using a pH meter. Basal gastric fluid pH was measured at 20 min intervals for 6 h in each horse and, with the exception of two measurements of 4.66 and 4.17, ranged from 1.42 to 2.41, with a mean pH of 1.88...
Cardiovascular effects of dopexamine HCl in conscious and halothane-anaesthetised horses.
Equine veterinary journal. Supplement    February 1, 1992   Issue 11 24-29 
Muir WW.The cardiovascular effects of serial increasing infusions of dopexamine HCl were investigated in six conscious (1, 2, 4, 6, 10 micrograms/kg bodyweight [bwt]/min) and eight (0.5, 1, 5, 10, 20 micrograms/kg bwt/min) halothane-anaesthetised horses. Dopexamine produced dose-dependent increases in heart rate, +dP/dtmax' -dP/dtmax and cardiac output, and a decrease in systemic vascular resistance in conscious and halothane-anaesthetised horses. Mean arterial blood pressure did not change in conscious horses but increased to a maximum value at 10 micrograms/kg bwt/min in halothane-anaesthetised hors...
Endothelium-dependent relaxation to alpha-methyl-5-hydroxytryptamine in isolated horse coronary arteries.
Japanese journal of pharmacology    January 1, 1992   Volume 58 Suppl 2 322P 
Obi T, Kabeyama A, Nishio A.No abstract available
Muscarinic receptor subtypes in equine tracheal smooth muscle.
Veterinary research communications    January 1, 1992   Volume 16, Issue 4 301-310 doi: 10.1007/BF01839329
Yu M, Robinson NE, Wang Z, Derksen FJ.Selective muscarinic receptor antagonists were used to identify muscarinic receptor subtypes in equine trachealis strips. The M1 receptor antagonist pirenzepine (10(-7) mol/L to 3 x 10(-5) mol/L) and the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, 10(-9) mol/L to 3 x 10(-7) mol/L3) dose dependently inhibited the contractile responses to electrical field stimulation (EFS) and exogenous acetylcholine (ACh). Schild plots yielded a pA2 value for pirenzepine vs ACh of 6.75 +/- 0.09, which is consistent with the affinity for M2 or M3 receptors, and a pA2 value for 4-DAMP vs ...
The pharmacology of local anesthetics.
The Veterinary clinics of North America. Equine practice    December 1, 1991   Volume 7, Issue 3 489-500 doi: 10.1016/s0749-0739(17)30482-0
Day TK, Skarda RT.Understanding of the pharmacology of local anesthesia is important for selection of a local anesthetic for use in equine standing surgery. In general, the action potential is inhibited by local anesthetics by preventing the influx of sodium ions across the axonal membrane. The physicochemical properties of each local anesthetic determine the onset of action, potency, and duration of action. Procaine, chlorprocaine, lidocaine, and mepivacaine are the local anesthetics still used clinically in horses; lidocaine is the most widely used. The future of equine local anesthesia may see the introducti...
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