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.
The effects of famotidine, ranitidine and magnesium hydroxide/aluminium hydroxide on gastric fluid pH in adult horses. 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. 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...
Muscarinic receptor subtypes in equine tracheal smooth muscle. 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. 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...
Chemical restraint for surgery in the standing horse. Chemical restraint can be a useful pharmacologic tool to assist the veterinarian performing surgery in the standing horse. The agents discussed impose minimal adverse side effects and are considered relatively safe when administered in the doses described. Acetylpromazine, the most widely used tranquilizer, produces mild sedation but no analgesia. The use of tranquilizers for surgical procedures requires the combined use of either a local anesthetic technique or a sedative-hypnotic or opiate to provide analgesia. Sedative-hypnotics such as xylazine and detomidine or opiates such as morphine an...
Comparison of the sedative effects of medetomidine and xylazine in horses. The sedative effects in horses of the new alpha 2 agonist medetomidine were compared with those of xylazine. Four ponies and one horse were treated on separate occasions with two doses of medetomidine (5 micrograms/kg bodyweight and 10 micrograms/kg bodyweight) and with one dose of xylazine (1 mg/kg bodyweight) given by intravenous injection. Medetomidine at 10 micrograms/kg was similar to 1 mg/kg xylazine in its sedative effect but produced more severe and more prolonged ataxia, and one animal fell over during the study. Medetomidine at 5 micrograms/kg produced less sedation but a similar deg...
Pharmacokinetics of caffeine and its metabolites in horses after intravenous, intramuscular or oral administration. The pharmacokinetics of caffeine (CAF) and its metabolites, dimethylxanthines, were examined in horses administered 2.5 mg/kg of CAF intravenously (i.v.), intramusculary (i.m.), or orally (p.o.). The plasma samples were extracted by Extrelut and the concentrations of CAF and metabolites were determined by high performance liquid chromatography (HPLC) with a short column. The pharmacokinetics of CAF after bolus i.v. injection were described by the assumption of a two-compartment model, and those of CAF after i.m. or p.o. administration were done by the assumption of a one-compartment model. The...
The influence of detomidine and epinephrine on heart rate, arterial blood pressure, and cardiac arrhythmia in horses. Detomidine (10 micrograms/kg and 20 micrograms/kg) was administered to seven horses with and without epinephrine infusion (0.1 microgram/kg/min) from 5 minutes before to 5 minutes after detomidine injection. One or more single supraventricular premature heartbeats were observed in three horses after detomidine administration. Epinephrine infusion did not modify the incidence of cardiac arrhythmias in detomidine-treated horses at the doses tested. Relatively high momentary peak systolic pressures were registered in some horses after detomidine administration during epinephrine infusion. The hig...
Analgesic and spasmolytic effects of dipyrone, hyoscine-N-butylbromide and a combination of the two in ponies. The analgesic and spasmolytic effects of dipyrone (Novalgin) (2500 mg/100 kg bodyweight) hyoscine-N-butylbromide (Buscopan) (20 mg/100 kg bodyweight) and a combination of both drugs were evaluated in a balloon-induced model of colic, using five ponies with caecal fistulae. The drugs were given intravenously and 0.9 per cent sodium chloride solution (5 ml/100 kg bodyweight) was used as a control. The physiological saline solution and dipyrone had no effect on caecal contractions. After the injection of hyoscine-N-butylbromide and the drug combination caecal contractions ceased within 30 seconds...
Effects of carbohydrates on the pharmacokinetics and biological activity of equine chorionic gonadotropin in vivo. The sialylation of eCG was examined to determine its influence on the in vivo metabolism and biological activity of the molecule. Sialic acid was decrementally removed from eCG by incubation with agarose-linked neuraminidase for varying time periods. Pharmacokinetic parameters for the disappearance of 4,000 IU (267 micrograms) of three desialylated eCG preparations (20%, 53%, and 80% sialic acid removed) and control eCG were determined in sheep. The clearance rate of eCG increased (p less than 0.05) with each decrement of sialic acid. The removal of 53% sialic acid enhanced the distribution of...
Participation of H1-receptors in histamine-induced contraction and relaxation of horse coronary artery in vitro. The mechanisms of histamine-induced contraction and relaxation were investigated in rings isolated from a middle part of the left descending coronary arteries of horses. Intact and endothelium-denuded preparations were compared. Rings of horse coronary arteries contracted in response to histamine in a concentration dependent manner, but some of them relaxed with lower concentrations and contracted with higher concentrations. Removal of the endothelium abolished the relaxation and potentiated the contraction. The pD2 values were 4.70 +/- 0.08 in the rings with intact endothelium and 4.95 +/- 0....
Dynamic baroreflex sensitivity in anesthetized horses, maintained at 1.25 to 1.3 minimal alveolar concentration of halothane. Dynamic baroreflex sensitivity for increasing arterial pressure (DBSI) was used to quantitatively assess the effects of anesthesia on the heart rate/arterial pressure relationship during rapid (less than or equal to 2 minutes) pressure changes in the horse. Anesthesia was induced with IV administration of xylazine and ketamine and maintained with halothane at a constant end-tidal concentration of 1.1 to 1.2% (1.25 to 1.3 minimal alveolar concentration). Systolic arterial pressure (SAP) was increased a minimum of 30 mm of Hg in response to an IV bolus injection of phenylephrine HCl. Linear regr...
Studies of meclofenamic acid and two metabolites in horses–pharmacokinetics and effects on exercise tolerance. The pharmacokinetics and the effects on treadmill exercise of the anti-inflammatory drug meclofenamic acid were studied in seven Standardbred horses after single intravenous and/or oral doses. The decline in plasma concentration after a single intravenous dose of meclofenamic acid (2.2 mg/kg b.wt) was described by a two-compartment open model. The average elimination half-life was 1.4 h, the apparent volume of distribution 0.14 l/kg and the plasma clearance 0.12 l/h kg. Absorption was the rate-limiting step after oral administration. Non-compartmental analysis showed a mean absorption time of ...
Clinical investigations of halothane and isoflurane for induction and maintenance of foal anesthesia. Fifty-eight foals were divided into two groups for study of aspects of the clinical anesthetic management of foals and to characterize effects of halothane (n = 30) and isoflurane (n = 28) in foals. There were no significant differences (P greater than 0.05) in the demographics of the two groups. Results of hemograms and biochemical analysis of venous blood samples before and after anesthesia were either not influenced or only mildly (clinically unimportant) affected by either agent. Like adult horses, foals have an increased PaCO2 when anesthetized with inhaled anesthetics. We could detect no...
Detection of reserpine in horses by high-performance liquid chromatography. A high-performance liquid chromatography (HPLC) assay was developed for the detection of reserpine. The assay was used to monitor the plasma concentrations of the drug given intramuscularly on one or two occasions to five horses. The blood concentrations of reserpine varied quite considerably between horses given the same dose of the drug. However, on average, reserpine could be detected consistently, and quantified, for 48 h after a single dose of 2.5 mg, and for a similar period after the second of two 2.5 mg doses given 13 d apart. Because of the apparently large variability in the pharmaco...
Effects of xylazine butorphanol on cecal arterial blood flow, cecal mechanical activity, and systemic hemodynamics in horses. A chronic model with an ultrasonic transit time blood flow probe and strain gauge force transducers implanted on the cecum was used to evaluate cecal mechanical activity and cecal arterial blood flow in 4 conscious adult horses. Intravenous administration of xylazine (1.1 mg/kg of body weight) significantly decreased heart rate and cardiac output, but significantly increased diastolic pulmonary arterial pressure, mean pulmonary arterial pressure, carotid arterial pressure, and central venous pressure. Lateral cecal arterial blood flow after xylazine administration was decreased substantially m...
Disposition of human drug preparations in the horse. I. Rectally administered indomethacin. A high-performance liquid chromatographic method to measure urinary indomethacin levels is described. In 0.5 ml urine, 1 micrograms/ml of indomethacin could be detected. Alkaline hydrolysis of urine resulted in the decomposition of indomethacin. When two suppositories of Indocid corresponding to 200 mg indomethacin were administered rectally to four horses the drug was rapidly absorbed and remained detectable in urine from 1 to 12 h. The excretion rate peaked after 2-3 h while the maximal concentration ranged from 18.5 to 80.6 micrograms/ml. Only 8 to 16% of the indomethacin dose was eliminate...
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...