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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.
Contractile response of horse deep dorsal penile vein to histamine. The present investigation was designed to evaluate the effect of histamine on isolated rings of horse deep dorsal penile vein. Under precontracted or basal conditions, histamine evoked an endothelium-independent contraction. Preincubation of the vein rings with the selective H1 receptor antagonist, mepyramine, shifted the concentration-response curve for histamine and to the H1 receptor agonist 2-pyridylethylamine to the right in a competitive manner. Pretreatment with cimetidine, a specific H2 receptor antagonist, did not modify the pEC50 and maximal contraction of the histamine response. Cim...
Pharmacokinetics of sulfamethoxazole and trimethoprim in donkeys, mules, and horses. To compare serum disposition of sulfamethoxazole and trimethoprim after IV administration to donkeys, mules, and horses. Methods: 5 donkeys, 5 mules, and 3 horses. Methods: Blood samples were collected before (time 0) and 5, 15, 30, and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 24 hours after IV administration of sulfamethoxazole (12.5 mg/kg) and trimethoprim (2.5 mg/kg). Serum was analyzed in triplicate with high-performance liquid chromatography for determination of sulfamethoxazole and trimethoprim concentrations. Serum concentration-time curve for each ani...
Comparison of intraosseous or intravenous infusion for delivery of amikacin sulfate to the tibiotarsal joint of horses. To establish the route of infusion (IV or intraosseous) that results in the highest concentration of amikacin in the synovial fluid of the tibiotarsal joint and determine the duration of peak concentrations. Methods: 21 horses. Methods: Regional perfusion of a limb on 15 horses was performed. Amikacin sulfate was infused into the saphenous vein or via intraosseous infusion into the distal portion of the tibia (1 g in 56 ml of lactated Ringer's solution) or proximal portion of the metatarsus (1 g of amikacin in 26 ml of lactated Ringer's solution). Amikacin concentrations were measured in seque...
Suspected adverse reactions to veterinary drugs reported in South Africa (January 1998 – February 2001). The Veterinary Pharmacovigilance Centre received 59 reports of suspected adverse drug reactions during the period January 1998 - February 2001. The number of reports received increased after the establishment of a formal procedure for recording and responding to reports. The number of reports received per species was: dogs 19, cats 15, cattle 7, sheep/ goats 6, chickens 4, pigs 3, horses 2 and giraffe 1. Many different types of adverse reactions were reported, including lack of efficacy, hypersensitivity, inappropriate use of products by non-veterinarians, known adverse effects and adverse eff...
Effects of repeated atropine injection on heart rate variability in Thoroughbred horses. To investigate the effects of repeated atropine injection on heart rate (HR) variability in resting Thoroughbred horses, two microg/ kg of atropine as parasympathetic nervous blockade was injected intravenously every 6 min to a total of 8 microg/kg after intravenous administration of 0.2 mg/kg of propranolol as sympathetic nervous blockade. We recorded electrocardiograms and obtained the HR, then evaluated variation in HR from the power spectrum in terms of low frequency (LF, 0.01-0.07 Hz) power and high frequency (HF, 0.07-0.6 Hz) power. Administration of atropine decreased parasympathetic ne...
Pharmacokinetics and toxic effects of lithium chloride after intravenous adminstration in conscious horses. To determine the pharmacokinetics and toxic effects associated with IV administration of lithium chloride (LiCl) to conscious healthy horses. Methods: 6 healthy Standardbred horses. Methods: Twenty 3-mmol boluses of LiCl (0.15 mmol/L) were injected IV at 3-minute intervals (total dose, 60 mmol) during a 1-hour period. Blood samples for measurement of serum lithium concentrations were collected before injection and up to 24 hours after injection. Behavioral and systemic toxic effects of LiCl were also assessed. Results: Lithium elimination could best be described by a 3-compartment model for 5 ...
Estimation of the probability for exceeding thresholds of urine specific gravity and plasma concentration of furosemide at various intervals after intravenous administration of furosemide in horses. To estimate the probability of concurrently exceeding thresholds for plasma concentration of furosemide and urine specific gravity after IV administration of furosemide in horses. Methods: 12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares. Methods: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after IV administration of 250 mg (first experiment) or 500 mg (second experiment) of furosemide. Urine was collected hourly between 1 and 6 hours after administration of furosemide at both doses. Concentrations of furosemide were...
Plasma pharmacokinetics and faecal excretion of ivermectin, doramectin and moxidectin following oral administration in horses. The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) w...
Analgesic effect of butorphanol and levomethadone in detomidine sedated horses. The analgesic potency of butorphanol 25 microg/kg bodyweight (BW) and levomethadone 100 microg/kg BW, administered together with detomidine 10 microg/kg BW, was measured in twelve Warmblood horses in a randomized, blinded cross-over study. Detomidine with saline 10 ml 0.9% was used as placebo. The nociceptive threshold was determined using a constant current and a pneumatic pressure model for somatic pair Detomidine alone and in combination with butorphanol or levomethadone caused a significant temporary increase (P < 0.05) of the nociceptive threshold with a maximum effect within 15 min an...
Comparison of 2 techniques for regional antibiotic delivery to the equine forelimb: intraosseous perfusion vs. intravenous perfusion. The purpose of this study was to compare the synovial fluid concentrations and pharmacokinetics of amikacin in the equine limb distal to the carpus following intraosseous and intravenous regional perfusion. The front limbs of 6 horses were randomly assigned to either intraosseous or intravenous perfusion. A tourniquet was placed distal to each carpus and the limb perfused with 500 mg of amikacin. Systemic blood samples and synovial fluid samples were collected over 70 min from the distal interphalangeal (DIP) joint, metacarpophalangeal joint, and digital flexor sheath. The tourniquet was remov...
Systematic analysis of acid, neutral and basic drugs in horse plasma by combination of solid-phase extraction, non-aqueous partitioning and gas chromatography-mass spectrometry. A sample preparation method for mass chromatographic detection of doping drugs from horse plasma is described. Bond Elut Certify (1 g/6 ml) is used for the extraction of 4 ml of horse plasma. Fractionation is performed with 6 ml of CHCl3-Me2CO (8:2) and 5 ml of 1% TEA-MeOH according to its property. Simple and effective clean-up based on non-aqueous partitioning is adopted to remove co-eluted contaminants in both acid and basic fractions. Two kinds of 1-(N,N-diisopropylamino)-n-alkanes are co-injected with the sample into the GC-MS system for the calculation of the retention index. Total recov...
Anti-remodelling drugs for the treatment of asthma: requirement for animal models of airway wall remodelling. 1. Airway wall remodelling (AWR), the structural change induced by acute and chronic inflammation in the airways, may be one of the most significant and difficult to reverse components of progressive asthma. 2. The mechanisms underlying the development of AWR are not known. Studies of only the most superficial wall structures of large airways can be conducted in living humans because of the degree of invasiveness required to measure airway structural changes. These studies reveal that currently available agents do not fully prevent or reverse AWR. Thus, animal models of asthma pathology may be...
The variability and repeatability of indices derived from the single-breath diagram for CO2 in horses with chronic obstructive pulmonary disease and the effect of lobelin hydrochloride on these indices. Several indices of ventilatory heterogeneity can be identified from the volumetric capnogram and its graphic presentation, the single-breath diagram for CO2 (SBD-CO2). Physiologically based indices of pulmonary function (VTE, VCO2, FACO2, VDBohr% VDBohr%, VD/VTE, A1/A2) were calculated for healthy horses (group I, n = 5) and for horses with subclinical (group II, n = 7) or clinically manifest chronic obstructive pulmonary disease (COPD) (group III, n = 8) during tidal breathing and after medication with lobelin hydrochloride (Lobelin). We investigated the variability and repeatability of the l...
Equine pulmonary and systemic haemodynamic responses to endothelin-1 and a selective ET(A) receptor antagonist. Based on previous in vitro studies, we hypothesised that endothelin (ET) would induce vasoconstriction in the pulmonary circululation of the horse and that this action would be mediated via ET(A) receptors. Pulmonary and systemic haemodynamic responses to endothelin-1 (ET-1), a potent vasoactive endogenous peptide, were investigated in 6 conscious, nonsedated horses at rest. Bolus i.v. injections of exogenous ET-1 (0.1, 0.2 and 0.4 microg/kg bwt) caused significant increases in pulmonary (PAP) and carotid (CAP) artery pressures, with peak increases of 79% and 51% for mean PAP and CAP, respecti...
Effects of 8-epi-PGF2alpha on isolated bronchial smooth muscle of healthy and heaves-affected horses. 8-Epi-PGF2alpha, a prostaglandin-like compound generated by oxidative stress, has been shown to be an in vitro bronchoconstrictor in airways from healthy laboratory animals and healthy humans, but it has never been studied in diseased airways. Here, the bronchoconstrictive capacity of 8-epi-PGF2alpha on isolated bronchial rings (BR) of healthy and heaves-affected horses was evaluated by comparing the maximal effect and the potency of 8-epi-PGF2alpha to those of (1) acetylcholine (ACh), (2) its stereoisomer PGF2alpha and (3) its synthetic receptor agonist, U46619. Furthermore, the potential cap...
Comparison of cefepime pharmacokinetics in neonatal foals and adult dogs. The pharmacokinetics of cefepime, a new fourth generation cephalosporin with enhanced antibacterial activity, was examined in neonatal foals and adult dogs. Cefepime was administered intravenously (i.v.) at a dose of 14 mg/kg to five neonatal foals and six adult dogs. Blood samples were collected in both groups of animals and plasma cefepime concentrations measured by reverse-phase high-performance liquid chromatography (HPLC). Cefepime concentrations in both groups of animals were described by a two-compartment pharmacokinetic model with elimination half-lives of 1.65 and 1.09 h for the foal ...
[Equine estrogens vs. esterified estrogens in the climacteric and menopause. The controversy arrives in Mexico]. It exists controversies about if the effects and benefits of the esterified estrogens could be similar to those informed for equines, because its chemical composition and bioavailability are different. Esterified estrogens has not delta 8,9 dehydroestrone, and its absorption and level of maximum plasmatic concentrations are reached very fast. In United States of America and another countries, esterified estrogens has been marketed and using for treatment of climacteric syndrome and prevention of postmenopausal osteoporosis, based on the pharmacopoiea of that country, but the Food and Drug admi...
Cerebrospinal fluid and serum concentrations of ponazuril in horses. Ponazuril was administered orally to 10 adult horses at 5 mg/kg body weight, once a day for 28 days. Blood was collected once a week from each horse from Days 0 through 35, daily from Days 35 through 42, and on Day 49. Cerebrospinal fluid (CSF) was also collected once a week from Day 0 through Day 49. Concentrations of ponazuril in the serum and CSF were determined, and pharmacokinetic calculations were performed. Ponazuril was readily absorbed following oral administration; and after 7 days of dosing, the serum concentration was 4.33 +/- 1.10 mg/L, and the mean CSF concentration was 0.162 +/-...
Efficacy of salmeterol xinafoate in horses with recurrent airway obstruction. To determine the onset, magnitude, and duration of bronchodilation after administration of aerosolized salmeterol xinafoate in horses with recurrent airway obstruction. Methods: Randomized controlled study Methods: 6 horses with recurrent airway obstruction. Procedure Horses received aerosolized salmeterol (210 microg) or no treatment, using a crossover design. Salmeterol was administered, using a mask designed for aerosol delivery in horses. Subjective rating of airway obstruction (RAO), maximal change in pleural pressure (deltaPplmax), and pulmonary resistance (RL) were determined at baselin...
Determination of oral dosage and pharmacokinetic analysis of flecainide in horses. To determine oral dosage and to evaluate the pharmacokinetics in horses of orally administered flecainide, an antiarrhythmic drug, the correlations between its plasma concentration and PR, QRS and QT intervals in equine electrocardiograms (ECG) were investigated. Six healthy horses were administered a randomly ordered dose of 4 or 6 mg/kg of flecainide acetate. The ECG was monitored (heart rate (HR), PR, QRS, and QT intervals) and blood was taken at timed intervals to measure the plasma flecainide concentrations pre- and post-administration. The maximum plasma concentration reached 1014+/-285 ...
Effect of topical 1% atropine sulfate on intraocular pressure in normal horses. OBJECTIVE: To determine the effect of topical 1% ophthalmic atropine sulfate on intraocular pressure (IOP) in ocular normotensive horses. Animals Studied Eleven clinically healthy horses. Procedures IOP was measured bilaterally twice daily, at 8 AM and 4 PM, for 5 days. No medication was applied for the first 2 days of the study. Thereafter, one eye of each horse was treated with 0.1 mL of topical 1% atropine sulfate ointment twice daily (7 AM and 7 PM) for 3 days. The contralateral eye served as a control. In eight of the horses, an additional IOP reading was taken 3 days following cessation ...
Disposition, elimination, and bioavailability of phenytoin and its major metabolite in horses. To determine pharmacokinetics and excretion of phenytoin in horses. Methods: 6 adult horses. Methods: Using a crossover design, phenytoin was administered (8.8 mg/kg of body weight, IV and PO) to 6 horses to determine bioavailability (F). Phenytoin also was administered orally twice daily for 5 days to those same 6 horses to determine steady-state concentrations and excretion patterns. Blood and urine samples were collected for analysis. Results: Mean (+/- SD) elimination half-life following a single IV or PO administration was 12.6+/-2.8 and 13.9+/-6.3 hours, respectively, and was 11.2+/-4.0 ...
Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses. To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses. Methods: 12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses). Methods: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis ...
Statistical evaluation of the regulatory guidelines for use of furosemide in race horses. The pharmacokinetic behavior of furosemide concentrations in performance horses is of great interest to the equine industry and equine researchers. Specifically, such information is useful for the evaluation of the existing guidelines in several racing jurisdictions and for the possible development of new guidelines for varying time periods after administration. We studied several approaches within the framework of nonlinear mixed effects models to increase the accuracy of evaluating these guidelines. Theoretical properties of the proposed methods were examined and the variances of the resulti...
The use of psychoactive agents in veterinary medicine. Psychotropic drugs are used by veterinary behavior specialists and general veterinary practitioners to treat behavior problems of companion animals. Dogs, cats, pet birds, horses, and zoo animals benefit from this type of therapy. However, many drugs used to treat anxiety or depression in animals were designed for use in human patients. Compounding is a critical step in adapting those medications for use in different species. Formulations that improve palatability or facilitate administration can often determine the success or failure of therapy in veterinary patients, and compounding is often...
The role of cyclooxygenase inhibitors in repair of ischaemic-injured jejunal mucosa in the horse. Cyclooxygenase inhibitors are administered to horses to prevent endotoxin-induced elaboration of prostaglandins. However, PGE2 and PGI2 stimulate repair of injured intestine. There are 2 isoforms of cyclooxygenase: COX-1, which constitutively produces prostaglandins and COX-2, which is induced by inflammation. We hypothesised that the nonspecific cyclooxygenase inhibitor flunixin meglumine would retard repair of ischaemic intestinal injury by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac, would permit repair as a result of continued COX-1 p...
In vitro pharmacologic effect of two endothelin-1 antagonists on equine colonic arteries and veins. To evaluate the effectiveness of 2 potential endothelin (ET)-1 antagonists in blocking the contractile responses of equine colonic vessels to increasing concentrations of ET-1. Methods: Mesenteric vessels from 6 clinically healthy horses. Methods: Colonic vessels (arterial and venous rings) were placed in organ baths with oxygenated Tyrode solution at 37 C. Each was attached to a force transducer interfaced with a polygraph, and 2 g of tension was applied and equilibrated for 45 minutes. Then, B-1 (PD 142893) and B-2 (PD 145065) ET-1 antagonists were tested. One ring from each vessel type was ...
Administration of ticarcillin in combination with clavulanic acid intravenously and intrauterinely to clinically normal oestrous mares. Ticarcillin and clavulanic acid (potassium clavulanate) were administered to normal oestrous mares intravenously (i.v.) at a dose of 50 and 1.67 mg/kg for ticarcillin and clavulanate, respectively. In a crossover design, the same drugs were administered intrauterine (i.u.) at a dose of 12.4 and 0.4 mg/kg for ticarcillin and clavulanate, respectively. The i.u. dose was administered in 100 mL of saline solution. Endometrial tissue biopsies and plasma samples were collected after drug administration for the determination of ticarcillin and clavulanate concentrations by high-pressure liquid chroma...
Faecal excretion profile of moxidectin and ivermectin after oral administration in horses. A study was undertaken to evaluate and compare faecal excretion of moxidectin and ivermectin in horses after oral administration of commercially available preparations. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups. Group I was treated with an oral gel formulation of moxidectin at the manufacturer's recommended therapeutic dose of 0.4 mg/kg b.w. Group II was treated with an oral paste formulation of ivermectin at the recommended dose of 0.2 mg/kg b.w. Faecal samples were collected at different times between 1 and 75 days ...
