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.
Cardiovascular effects of xylazine and detomidine in horses. The cardiovascular effects of xylazine and detomidine in horses were studied. Six horses were given each of the following 5 treatments, at 1-week intervals: xylazine, 1.1 mg/kg, IV; xylazine, 2.2 mg/kg, IM; detomidine, 0.01 mg/kg, IV; detomidine, 0.02 mg/kg, IV; and detomidine, 0.04 mg/kg, IM. All treatments resulted in significantly decreased heart rate, increased incidence of atrioventricular block, and decreased cardiac output and cardiac index; cardiac output and cardiac index were lowest following IV administration of 0.02 mg of detomidine/kg. Mean arterial pressure was significantly redu...
Detomidine reduces the plasma catecholamine, but not cortisol concentrations in horses. Single doses of the alpha 2-adrenergic sedative-analgesic drug, detomidine (10 micrograms/kg, n = 7; 20 micrograms/kg, n = 9), were administered IV to adult horses. Plasma concentrations of adrenaline, noradrenaline, the catecholamine metabolites 3,4-dihydroxyphenylglycol (DHPG) and 3,4-dihydroxyphenylacetic acid (DOPAC), and cortisol were determined before the medication and 30 minutes after it. The plasma concentrations of noradrenaline and the catecholamine metabolites decreased significantly after administration of both 10 micrograms/kg and 20 micrograms/kg of detomidine. Plasma adrenaline...
Pharmacodynamics and pharmacokinetics of miloxicam in the horse. The novel non-steroidal anti-inflammatory drug (NSAID) miloxicam was administered intravenously to six New Forest ponies at a dosage rate of 0.6 mg/kg in a two-part cross-over study. In each part, three horses received miloxicam and three were given a placebo preparation. The actions of miloxicam, compared to placebo, were assessed in a carrageenan-sponge model of acute inflammation. The rise in skin temperature over the site of the acute inflammatory reaction was less in treated ponies, but differences were not statistically significant. Concentrations of the enzymes acid phosphatase (AP) and...
Effects of conjugated equine estrogen with and without three different progestogens on lipoproteins, high-density lipoprotein subfractions, and apolipoprotein A-I. The effects of conjugated equine estrogen and subsequent cyclical progestogen supplementation on lipoprotein and apolipoprotein A-I levels were investigated in three groups of postmenopausal women. Unopposed conjugated equine estrogen (0.625 mg) lowered total cholesterol 4-8% and low-density lipoprotein (LDL) cholesterol 12-19% below pre-treatment levels in all three groups. Levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I were increased 9-13 and 9-18%, respectively, with unopposed estrogen. The increase in HDL cholesterol was mainly due to increases in the high-dens...
Characterization of bromhexine and ambroxol in equine urine: effect of furosemide on identification and confirmation. The purpose of this study was two-fold: (1) to develop a simple and sensitive screening procedure for identifying and confirming bromhexine and ambroxol and, (2) to determine the effect of furosemide on the detection of bromhexine, ambroxol, or their metabolites in urine. Female horses (450-550 kg) treated with bromhexine or ambroxol (1 g, p.o.) were used. Urine samples were collected up to 48 h post-drug administration and analysed. Blind samples were used in evaluating the sensitivity of these methods and reproducibility of the results. Bromhexine and ambroxol were extensively metabolized in...
Some physiological and pharmacological factors affecting uterine motility as measured by electromyography in the mare. Two intact and 2 ovariectomized mares aged 3-16 years had bipolar electrodes implanted in the myometrium to measure electromyographic (emg) activity during normal and exogenously simulated (with oestrogen and progesterone) cyclical activity (anoestrus, transition, oestrus and dioestrus). Oxytocin, cloprostenol, propantheline bromide and clenbuterol were administered during each cycle stage. In 1 mare, emg activity was recorded during natural breeding (4 times) and through the first 20 days of pregnancy. Simultaneous intrauterine pressure recordings (IUP) using an open tipped catheter system we...
Regional anesthesia. Organ toxicity from local anesthetic agents is rare. This makes these agents an attractive option in the high-risk patient. Complications associated with local anesthetics are related to overdosage. Overdosage with local anesthetic agents administered epidurally may cause motor paralysis and hind-limb weakness. Systemic signs of local anesthetic overdosage include changes in central nervous system activity (excitement or depression), muscle tremors, and hypotension. Because the dose required to produce these effects in the horse is high (12 mg/kg), this complication is uncommon. Few side effec...
Pharmacokinetics of gentamicin in newborn to 30-day-old foals. Gentamicin sulfate, equivalent to 4 mg of gentamicin base/kg of body weight, was administered IV to 6 Thoroughbred foals on day 1 (12 to 24 hours of age) and at 5, 10, 15, and 30 days after birth. On day 40 after parturition, gentamicin was given to the mares at a dosage similar to that used in foals. Decay of serum gentamicin concentrations was best described by a 2-compartment model. Among foals, the overall elimination rate constant at 30 days of age was significantly (P less than 0.05) greater than at days 1, 10, and 15. There was, however, no difference in the overall elimination rate con...
Efficacy of avermectin B1 given orally against equine intestinal strongyles and Onchocera microfilaria. Three groups of horses and ponies (N = 13, 13 and 12) were treated with ivermectin paste (0.2 mg/kg p.o.), avermectin B1 solution (0.2 mg/kg p.o.), or fenbendazole suspension (10 mg/kg via nasogastric tube). The avermectin B1 was a 1% solution in a propylene glycolglycerol formal base. Faecal strongyle egg counts were performed before, and 14, 28, 42, 56 and 70 d, after treatment. Full-thickness skin biopsies from the neck, pectoral and umbilical regions were examined for Onchocera microfilaria before treatment, and again 14 and 70 d later. Ivermectin therapy produced a significant (P less tha...
[The treatment basis for anticoagulants in horses]. The pharmacokinetics of racemic phenprocoumon were studied in 8 adult horses after the single intravenous and oral administration of 0.75 mg/kg. After i.v. administration the plasma concentration of phenprocoumon showed a biphasic decline in time. The pharmacokinetics were calculated on the two-compartment open model. The average plasma half-life (beta-phase) was 22 hours, the apparent volume of distribution was 0.61 l/kg, Cltot was 25.2 ml/kg/h (13.9-40.9 ml/kg/h). The systemic bioavailability of oral phenprocoumon was 97.6%, Tmax was found to be 4-12 hours. The effect of phenprocoumon on the...
Modulation of an adhesion-related surface antigen on equine neutrophils by bacterial lipopolysaccharide and antiinflammatory drugs. The essential role of the CD11/CD18 family of leukocyte adhesion molecules (LeuCams) in neutrophil-substrate adhesion is well documented. We have found that a monoclonal antibody designated 60.3 (MoAb 60.3) that recognizes the common beta-subunit (CD18) on human neutrophils (PMN) also recognizes a surface antigen on equine PMN. Antigen expression as assessed by immunofluorescence flow cytometry was enhanced by zymosan-activated serum (ZAS) or phorbol 12-myristate 13-acetate (PMA) stimulation. Pretreatment of equine PMN with MoAb 60.3 inhibited ZAS-stimulated aggregation, indicating that the mo...
Effect of antimicrobial solution lavage on the palmar digital tendon sheath in horses. Sixteen horses were allotted to 4 groups of 4 horses each to evaluate the effect of tendon sheath lavage with 4 solutions (balanced electrolyte solution, 0.1% povidone-iodine, 0.5% povidone-iodine, and 0.5% chlorhexidine). The synovitis caused by 0.1% povidone-iodine lavage was not appreciably worse than that caused by balanced electrolyte solution lavage, but the 0.5% povidone-iodine and chlorhexidine lavages caused severe synovitis, and, therefore, should not be used for tendon sheath lavage.
Synovial fluid pH, cytologic characteristics, and gentamicin concentration after intra-articular administration of the drug in an experimental model of infectious arthritis in horses. Chemical and cytologic effects and bactericidal activity of gentamicin in septic synovial fluid were evaluated in an experimental model of infectious arthritis in horses. Septic arthritis was induced by inoculation of approximately 7.5 X 10(6) colony-forming units of Escherichia coli into 1 antebrachiocarpal joint in each of 16 clinically normal adult horses. Clinical signs of septic arthritis were evident 24 hours after inoculation. Horses were allotted to 3 groups: group-1 horses (n = 5) each were given 150 mg of gentamicin (50 mg/ml; 3 ml) intra-articularly (IA); group-2 horses (n = 5) each...
Evaluation of high performance liquid chromatography (HPLC), enzyme linked immunosorbent assay (ELISA) and particle concentration fluorescence immunoassay (PCFIA) methods for the screening, quantitation and pharmacokinetic study of furosemide in horses. Equine plasma and urine samples were analyzed by using a high-performance liquid chromatography (HPLC), enzyme-linked immunosorbent assay (ELISA) and particle concentration fluorescence assay (PCFIA). Although ELISA and PCFIA were rapid, simple and sensitive for the screening of furosemide, they did not give reproducible quantitative results. The HPLC method, which required relatively longer analysis time, provided simple and reproducible quantitative analysis of furosemide in plasma and urine. The performance of the three methods was compared for the quantitation of furosemide in plasma obtai...
The effects of phenylbutazone on the intestinal mucosa of the horse: a morphological, ultrastructural and biochemical study. Phenylbutazone, a non-steroidal anti-inflammatory drug known to produce intestinal erosions, was administered intravenously (13.46 mg/kg bodyweight) to 12 horses which were killed after 24, 48, 72 and 96 h. Eight untreated horses served as controls. Annular erosions in the duodenum and mucosal necrosis in the colon were seen after 48 h which progressed in severity. The erosions were characterised by sloughing of the surface epithelium, subepithelial cleft and bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries and microthrombosis. Large numbers o...
The effect of phenylbutazone on the plasma disposition of penicillin G in the horse. A pilot study in two ponies showed that the plasma concentrations of intramuscularly administered procaine penicillin were higher if phenylbutazone was administered concurrently. In two other trials, each involving five horses, intravenous sodium penicillin was administered with and without concurrent intravenously injected phenylbutazone, and procaine penicillin was injected intramuscularly with and without oral phenylbutazone. In both cases the plasma concentrations of penicillin were higher when phenylbutazone was given. The pharmacokinetic parameters indicated that the effect was probably ...
Influence of furosemide on the detection of flunixin meglumine in horse urine samples. The possibility of false negative results from TLC when a diuretic is administered concomitantly with flunixin was studied. Samples were subjected to solvent extraction from acidic aqueous solutions; duplicate samples were also subjected to alkaline hydrolysis at pH 12.5. The internal standard was flufenamic acid. The quantification of flunixin was performed by HPLC and the results confirmed by GC/MS. The data show that furosemide influences the urinary concentration of flunixin.
Plasma disposition and tolerance of aditoprim in horses after single intravenous injection. Aditoprim, a broad spectrum antimicrobial agent acting as a reversible dihydrofolate reductase inhibitor, was intravenously injected into four 12 to 24-year old horses at a dosage of 5 mg/kg b. w. Blood samples were collected over a 48-hour period after drug injection, and the separated plasma samples were assayed for aditoprim by high performance liquid chromatography. The body temperature, heart rate, respiration rate, and behaviour were recorded during the experiment. The bilirubin and urea concentrations were also determined in several plasma samples, and liver function tests were carried ...
Effect of clenbuterol on arterial oxygen tension in the anaesthetised horse. In horses in dorsal recumbency, spontaneously breathing oxygen, with halothane at a constant end-tidal concentration, the arterial oxygen tension (PO2) increased from 9.9 +/- 0.3 SEM kPa to 21.7 +/- 4.0 kPa with 0.8 micrograms kg-1 clenbuterol and to 29.1 +/- 3.8 kPa with 2.4 micrograms kg-1 clenbuterol. In horses initially in dorsal recumbency then turned to sternal recumbency the PaO2 rose to 54.0 +/- 3.0 kPa, but this rise was unaffected by clenbuterol administration. The response in dorsal recumbency was consistent with clenbuterol counteracting the factor postulated to direct the pulmonar...
Propafenone kinetics in the horse. Comparative analysis of compartmental and noncompartmental models. The propafenone kinetics after intravenous (i.v.) administration have been studied in the horse by a comparative analysis of compartmental and noncompartmental models. The pharmacokinetic parameters showed a large distribution (Vdss = 1021 +/- 211 L) and a high clearance (CI = 7019 +/- 1746 mL/min) of the drug. The plasma concentrations were very low, under 1 microgram/mL, in most cases; after 30 min these concentrations can be considered as nonefficient for the treatment of arrhythmia. There were no significant differences between pharmacokinetic parameters found with the use of compartmental...
Use of gonadotropin-releasing hormone for hastening ovulation in transitional mares. Natural GnRH and its analog have potential for hastening ovulation in mares. A study was conducted to evaluate the efficacy of a GnRH agonist given either as an injectable or s.c. implant for induction of ovulation in mares. Forty-five seasonally anestrous mares (March) were assigned to one of three groups (n = 15/group): 1) untreated controls; 2) i.m. injection of the GnRH agonist buserelin at 12-h intervals (40 micrograms/injection for 28 d or until ovulation) and 3) GnRH agonist administered as a s.c. implant (approximately 100 micrograms/24 h for 28 d). Six mares per group were bled on d 0...
The influence of furosemide on plasma elimination and urinary excretion of drugs in standardbred horses. A study of the effects of intravenous administration of either 150 mg or 250 mg of furosemide to standardbred mares pre-treated with other drugs was undertaken to determine whether a unique pattern of drug elimination into urine and from plasma for each compound occurred. Furosemide significantly reduced the plasma concentrations of codeine compared to control 2-6 h after furosemide administration. In contrast, the plasma concentrations of theophylline, phenylbutazone, pentazocine, guaifenesin and flunixin were not markedly altered by furosemide. In the case of acepromazine, clenbuterol and fe...
Pharmacodynamic evaluation of the peripheral pain inhibition by carprofen and flunixin in the horse. Carprofen, flunixin meglumine and placebo in the form of a physiological solution of sodium chloride were tested in an open randomised cross-over trial for analgesic efficacy in horses with two external skin-stimulation systems. Both systems, the withers model and the "heating element" model, were compared in order to find an optimal way to measure pain perception after stimulating the skin with high temperature. No analgesic effect of flunixin or carprofen could be demonstrated when using the withers model. In the "heating element" model, a 1.1 mg/kg i.v. dose of flunixin meglumine failed to ...
Effects of indomethacin on neural and myogenic components in equine airway smooth muscle. Equine airway smooth muscle is innervated by vagal efferents and, in addition, displays spontaneous mechanical activity. The preparation thus appears to contain at least two discrete excitable components, the cholinergic neural elements and the smooth muscle membrane. Indomethacin (INDO), a cyclooxygenase (CO) inhibitor, exerts a considerable potentiation of function in this preparation. The latter may be effected indirectly, through loss of the inhibitory effect of endogenous prostaglandin E2 (PGE2) on neural acetylcholine release and through direct effects on smooth muscle of the generally a...
[Anesthesia by injection of xylazine, ketamine and the benzodiazepine derivative climazolam and the use of the benzodiazepine antagonist Ro 15-3505]. 25 horses which entered the clinic for minor surgery, received ketamine (2.2 mg/kg i.v.) for induction of anesthesia after previous sedation with xylazine (1.1 mg/kg i.v.). As soon as the horses were in the lateral recumbency, the benzodiazepine derivate climazolam was administered at a dose of 0.1 mg/kg i.v. (10 horses) or 0.2 mg/kg i.v. (15 horses). The anesthesia was maintained with repeated injections of ketamine (1.1 mg/kg i.v. every 9-12 minutes). At the end of the surgery, 20 minutes after the last ketamine injection, Ro 15-3505, a benzodiazepine antagonist, was injected at a dose of 0....
Haemodynamic changes during sedation in ponies. The cardiovascular changes induced by several sedatives were investigated in five ponies with a subcutaneously transposed carotid artery by means of cardiac output determinations (thermodilution technique), systemic and pulmonary artery pressure measurements (direct intravascular method) and arterial blood analysis (blood gases and packed cell volume). The cardiovascular depression (decrease in systemic blood pressure and cardiac output) was long lasting (greater than 90 min) after administration of propionylpromazine (0.08 mg/kg intravenous (i.v.)) together with promethazine (0.08 mg/kg i.v.)...
An evaluation of the multiple-breath nitrogen washout as a pulmonary function test in horses. Multiple-breath nitrogen washouts (MBNW) were performed with 29 light horses. Seven normal horses were used to examine the reproducibility, and 22, ranging from normal to severely diseased, were used to examine the changes in chronic obstructive pulmonary disease (COPD) and the effect of a bronchodilator, salbutamol, on the distribution of ventilation. The MBNW were analyzed using the functional residual capacity (FRC), end-tidal N2 concentration of the final breath of the MBNW (FETN2,fb), end-tidal N2 concentration when the cumulative expired volume was equal to body weight (FETN2,bw), lung c...
Effect of calcium-channel blockers and salbutamol on the isolated mare uterus–interaction with the calcium agonist Bay K 8644. The effects of nifedipine, verapamil and diltiazem were investigated in the isolated mare uterus in comparison with salbutamol. All the calcium-channel blockers and salbutamol inhibited the spontaneous, KC1- and electrically induced contractions; nifedipine and salbutamol were the most potent compounds. The calcium agonist Bay K 8644 (10(-8)-10(-6) mol/l) competitively antagonized the inhibitory effect of nifedipine (pA2 value = 8.54 +/- 0.06), whereas it was only slightly or totally ineffective against verapamil, diltiazem and salbutamol. These results indicate that calcium-channel blockers a...
Antagonism in isolated equine digital vessels of contraction induced by epinephrine in the presence of hydrocortisone and an aqueous extract of black walnut (Juglans nigra). Prazosin, isoxsuprine, and nifedipine were screened for ability to reverse contraction of isolated equine digital vascular strips produced by epinephrine (Epi) in the presence of hydrocortisone (Hc) and an aqueous extract of black walnut (Juglans nigra) (BW). Two arteries and two veins from each of three horses for each drug (n = 9) were maintained in isolated tissue baths in Krebs' bicarbonate buffer with 95% oxygen at 37 degrees C. Six-point Epi concentration-response (C-R) curves were obtained for each vessel in the presence of Hc, BW, and the appropriate vehicle. This was repeated for each...
Pharmacokinetic disposition of an immediate-release aminophylline and a sustained-release theophylline formulation in the horse. The pharmacokinetic disposition of theophylline was determined by high-performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate-release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained-release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (lambda z), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 +/- 0.01 h-1, 0.80 +/- 0.0...