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.
Interactions between chloramphenicol, acepromazine, phenylbutazone, rifampin and thiamylal in the horse. The potential for interactions between chloramphenicol, phenylbutazone, acepromazine and thiamylal and chloramphenicol, rifampin, and phenylbutazone were evaluated in two groups of experiments. In the first, five horses were given thiamylal intravenously (iv) (6.6 mg/kg) after pretreatment with acepromazine, and the time of recumbency was determined. Administration of chloramphenicol iv (25 mg/kg) 1 h prior to anaesthesia significantly lengthened the recumbency time from 21.8 +/- 4.8 mins to 36.0 +/- 8.3 mins. There was an apparent but not statistically significant decrease in recumbency time ...
The effect of detomidine hydrochloride on the electrical activity of uterus in pregnant mares. The effect of detomidine on the electrical activity of the uterus was studied during the last trimester of pregnancy in 6 mares. The effect was observed in 3-5 min after the i.m. injection and it lasted for 50-70 min. 20 and 40 micrograms/kg b.w. doses of detomidine decreased the myometrial electrical activity, whereas 60 micrograms/kg dose did not have any effect on the activity. The results suggested that 20, 40 and 60 micrograms/kg b.w. doses of detomidine can be administered to mares during the last trimester of pregnancy without the risk of abortion induced by increased uterine electrical...
Disposition and excretion of flunixin meglumine in horses. The disposition of flunixin meglumine administered IV at a dosage of 1.1 mg/kg was described by a 2-compartment model; the alpha and beta half-lives (t1/2) were 0.61 and 1.5 hours, respectively. When administered IV at a rate of 2.2 mg/kg, the disposition was best described by a 3-compartment model, and the alpha, beta, and lambda t1/2 were 0.16, 1.52, and 6.00 hours, respectively. The zero-time plasma concentrations after flunixin meglumine was administered at 1.1 and 2.2 mg/kg were 9.3 +/- 0.76 and 21.5 +/- 7.4 mg/L, respectively. The bioavailability after oral administration of 1.1 mg/kg wa...
Detomidine-butorphanol sedation in equine clinical practice. Combinations of detomidine (mean dose rate 13 micrograms/kg) and butorphanol (mean dose rate 26 micrograms/kg) were used to sedate 61 horses for a variety of surgical or diagnostic procedures in general equine practice. Three horses were sedated on more than one occasion. The degree of sedation was graded from 3 to 0 (deep sedation to no effect) and any side effects were recorded. Forty-three per cent of the horses were graded 3, 46 per cent were graded 2, 8 per cent were graded 1 and 3 per cent were graded 0. Bradycardia and ataxia were the major side effects. The combination was judged to be...
Serum and synovial fluid steady-state concentrations of trimethoprim and sulfadiazine in horses with experimentally induced infectious arthritis. The tarsocrural joints of 11 horses were inoculated with 1.2 to 2.16 x 10(6) viable Staphylococcus aureus organisms susceptible to a trimethoprim-sulfadiazine (TMP-SDZ) combination with minimal inhibitory concentration (MIC) of 0.25 micrograms of TMP/ml and 4.75 micrograms of SDZ/ml. Antimicrobial treatment consisted of oral administration of a TMP-SDZ combination--30 mg/kg of body weight given once daily (group-1 horses) or 60 mg/kg given as 30 mg/kg every 12 hours (group-2 horses). Paired serum and synovial fluid samples were obtained before intra-articular inoculation with the S aureus, aft...
Combined use of detomidine with opiates in the horse. The effects of administration of one of four opiates (pethidine 1 mg/kg bodyweight (bwt), morphine 0.1 mg/kg bwt, methadone 0.1 mg/kg bwt, and butorphanol 0.05 mg/kg bwt) given intravenously to horses and ponies already sedated with detomidine (10 micrograms/kg bwt) were investigated. Behavioural, cardiovascular and respiratory effects of the combinations were compared with those occurring with detomidine alone. Addition of the opiate increased the apparent sedation and decreased the response of the animal to external stimuli. At doses used, butorphanol produced the most reliable response. Sid...
Detomidine: a preliminary analysis of its duration of action in the horse by variable interval responding. Variable interval (VI) reinforcement scheduling is a specific type of operant conditioning that is sensitive to drug effects even when overt clinical signs of the drug have diminished. Six horses were conditioned to break a light beam with a head-bobbing movement and this behaviour was reinforced with a reward of clean oats (approximately 30 mg/reinforcement). Initial training procedures included familiarisation with the behavioural equipment and fixed-ratio reinforced scheduling. To establish baseline rates of behaviour, the horses were converted to a variable interval (60 secs) reinforcement...
Neuromuscular and cardiovascular effects of atracurium administered to healthy horses anesthetized with halothane. Neuromuscular and cardiovascular effects of atracurium, a nondepolarizing neuromuscular blocking agent, were evaluated in 10 halothane-anesthetized adult horses. Hind limb digital extensor tension (hoof twitch) was measured with a strain gauge to quantitate the muscle relaxant effects of atracurium. Response of facial muscles was compared with hoof twitch. Five injections of atracurium were given. Initial mean (+/- SEM) dosage of 0.07 +/- 0.01 mg of atracurium/kg of body weight caused 98.6 +/- 0.8% reduction of the preinjection hoof twitch. Subsequent dosages of 0.04 +/- 0.003 mg/kg induced a ...
Objective assessment of detomidine-induced analgesia and sedation in the horse. The effects of detomidine, a veterinary sedative analgesic, were studied in the horse. Novel objective techniques were employed to assess the analgesic and sedative potency of this compound. Intravenous doses of 0.010, 0.020 and 0.040 mg/kg were administered to eight adult Thoroughbred racehorses according to a double-blind crossover design. Analgesia was measured by determining the latency to onset of the skin twitch and hoof withdrawal reflexes following noxious thermal stimulation of the withers and fetlock, respectively. Sedation was assessed by quantifying spontaneous locomotor activity i...
The effect of various antibacterial preparations on the in vitro morphology and chemotactic response of equine neutrophils. Two independent assay systems were used to study the effect of three antibacterial preparations on in vitro morphology and chemotaxis of equine neutrophils. Incubation of neutrophils with high (200 micrograms/ml) and medium (20 micrograms/ml) concentrations of neomycin impaired their response to standard chemoattractants. Trimethoprim/sulfadoxine (0.4/2.0 micrograms/ml-40/200 micrograms/ml) and benzylpenicillin (0.25-25 micrograms/ml) had no effect. Neutrophils collected from geldings 2 and 24 h after neomycin (5 mg/kg) administration had impaired responses to standard chemoattractants. Benzyl...
Effects of xylazine and acepromazine on bronchomotor tone of anaesthetised ponies. The effects of xylazine (an alpha 2-adrenoceptor agonist) and acepromazine (an alpha-adrenoceptor antagonist) on bronchomotor tone were investigated in seven anaesthetised, apnoeic ponies using a computer aided forced oscillation technique, which separates changes in bronchial calibre from changes in lung volume. Both agents produced bronchodilatation and a decrease in lung volume.
Plasma and synovial fluid concentrations of gentamicin in horses after intra-articular administration of buffered and unbuffered gentamicin. The concentration of gentamicin in plasma and synovial fluid of normal adult horses was measured periodically for 24 hours after IV (2.2 mg/kg of body weight), intra-articular (IA; 150 mg), and simultaneous IV and IA administrations. Gentamicin also was buffered with sodium bicarbonate (3 mEq) and then was administered IA and simultaneously IV and IA. Synovial fluid specimens were obtained via an indwelling catheter placed into the antebrachiocarpal joint. The peak mean plasma gentamicin concentration (8.30 micrograms/ml) after IV administration was significantly (P less than 0.05) greater tha...
Effect of gentamicin sulfate and sodium bicarbonate on the synovium of clinically normal equine antebrachiocarpal joints. The effect of gentamicin sulfate, unbuffered and buffered with sodium bicarbonate, on synovial fluid and membrane of clinically normal equine joints was evaluated. Thirty-six adult horses with clinically normal antebrachiocarpal joints were allotted to 6 treatment groups of 6 horses each. One antebrachiocarpal joint in each horse was chosen for treatment. Group-1 horses were given gentamicin (3 ml; 50 mg/ml); group-2 horses were given sodium bicarbonate (3 ml; 1 mEq/ml); group-3 horses were given gentamicin (3 ml; 50 mg/ml) and sodium bicarbonate (3 ml; 1 mEq/ml); group-4 horses were not treat...
Influence of the autonomic nervous system in the horse urinary bladder. alpha and beta-adrenergic receptors in detrusor muscle and bladder base of horses were investigated by in vitro responses of smooth muscle strips to exogenous agonist and antagonist drugs. Noradrenaline, isoprenaline and salbutamol induced relaxation of detrusor muscle strips which was significantly inhibited by propranolol and butoxamine suggesting that the response is mediated by beta-2 adrenergic receptors. In the urinary bladder base noradrenaline, phenylephrine and B-HT 920 induced strong contractile effects. These contractile responses were inhibited by the alpha antagonist phenoxybenzam...
Hemodynamic and respiratory responses in halothane-anesthetized horses exposed to positive end-expiratory pressure alone and with dobutamine. The influence of positive end-expiratory pressure (PEEP) on the alveolar-arterial O2 tension difference [P(A-a)O2], physiologic right-to-left shunt fraction, physiologic dead space-to-tidal volume ratio, and hemodynamic variables was studied in halothane-anesthetized horses maintained in dorsal recumbency during controlled ventilation. Dobutamine was used to minimize the adverse cardiovascular consequences of PEEP. Six adult horses were anesthetized, using xylazine (2.2 mg/kg of body weight, IM), guaifenesin (50 mg/kg, IV), thiamylal Na (4.4 mg/kg, IV), and halothane (1.5 to 2% inspired) in 10...
Effect of butorphanol, pentazocine, meperidine, or metoclopramide on intestinal motility in female ponies. Effect of butorphanol, pentazocine, meperidine, and metoclopramide on jejunal and pelvic flexure myoelectric and mechanical activity in 4 female ponies was investigated. The agent to be tested or saline solution was administered IV at the start of a 6-hour recording trial. In the jejunum, duration between activity fronts of regular spiking activity, defined as the length of the migrating myoelectric complex (MMC), was measured. The average duration of the MMC during control trials was 150 +/- 46 minutes. The average duration of the MMC after meperidine, butorphanol, pentazocine, and metoclopra...
Comparative pharmacokinetics of yohimbine in steers, horses and dogs. In steers, horses and dogs, the comparative pharmacokinetics of yohimbine were determined using model-independent analysis. The intravenous dose of yohimbine was 0.25 mg/kg of body weight in steers, 0.075 or 0.15 mg/kg in horses, and 0.4 mg/kg in dogs. The mean residence time (+/- SD) of yohimbine was 86.7 +/- 46.2 min in steers, 106.2 +/- 72.1 to 118.7 +/- 35.0 min in horses, and 163.6 +/- 49.7 min in dogs. The mean apparent volume of distribution of yohimbine at steady state was 4.9 +/- 1.4 L/kg for steers, 2.7 +/- 1.0 to 4.6 +/- 1.9 L/kg for horses, and 4.5 +/- 1.8 L/kg for dogs. The total ...
Dose related effects of the kappa agonist U-50, 488H on behaviour, nociception and autonomic response in the horse. Current opiate receptor theory suggests that kappa agonists should provide good analgesia without producing marked central nervous system stimulation. U-50,488H is an experimental narcotic analgesic that is a selective kappa agonist. In the present study, U-50,488H produced good analgesia in horses using both the skin twitch and hoof withdrawal reflex assays. Further, the analgesia was relatively long lasting (120 mins) compared to other mu-agonists tested in horses. The locomotor response to U-50,488H was less than observed with ethylketazocine and butorphanol, and has yielded the smallest lo...
Dose-dependent plasma elimination of subcutaneously administered calcium heparin in horses. Pharmacokinetic parameters for subcutaneous low dose heparin in horses have been determined. Four groups of five and one group of eleven mature, healthy horses of various breeds were given single subcutaneous injections of 60, 80, 100, 125, and 150 units of calcium heparin/kg of body weight (U/kg) in the pectoral region. Jugular blood samples were collected prior to, and at hourly intervals for 12 h after injection. Heparin plasma concentrations were measured using a commercially available amidolytic assay. Peak concentrations 4 h after administration were 0.021 +/- 0.016 (mean +/- SD) units o...
Enterohepatic circulation of lorazepam and acetaminophen conjugates in ponies. Adult female ponies (130-225 kg) with chronically implanted external biliary fistulas (T-tubes) participated in three-way cross-over studies using either i.v. lorazepam (10 mg) or acetaminophen (2 g), two model drugs biotransformed mainly by hepatic conjugative reactions. The objectives were to determine the systemic pharmacokinetics, urinary and biliary excretion and degree of enterohepatic circulation (EHC) of these compounds. Trial conditions were: A: EHC intact, with blood and urine, but not bile, collected after i.v. drug administration; B: EHC interrupted, with blood, urine and bile coll...
[The use of a beta 2-mimetic agent (clenbuterol) in equine pregnancy disorders and obstetrics]. A clinical study about the effects of a beta 2-mimetic agent (Clenbuterol) in mares with pregnancy disorders or disorders during the periparturient period (n = 34) is reported. In general, a single dose of 0.3 mg Clenbuterol given i.v. induces sufficient tocolysis. Subsequent doses or follow-up treatment depend upon individual development during dystocia, indication of treatment and clinical preparturient status (dorsoflexio uteri ante partum, abortus imminens, preparturient labor pains).
Effects of halothane anesthesia on the clearance of gentamicin sulfate in horses. Inhalation anesthetics decrease the clearance of some drugs that are eliminated by renal excretion. The purpose of the study reported here was to investigate the effects of halothane anesthesia on the pharmacokinetics and urinary excretion of gentamicin sulfate, using the horse as a model. Using a crossover design, pharmacokinetic values after a single IV dose of gentamicin (4 mg/kg) were compared in halothane-anesthetized and unanesthetized horses. Compared with unanesthetized horses, the anesthetized horses had significant decreases in total body clearance (P less than 0.01) and apparent vol...
Plasma heparin values and hemostasis in equids after subcutaneous administration of low-dose calcium heparin. Different doses of heparin were given to equids SC to establish 0.05 to 0.20 U of heparin/ml of plasma. Plasma heparin values and antithrombin III activities were assayed, using chromogenic substrate methods. Activated partial thromboplastin and thrombin times were determined, using conventional coagulation assays. Tests were run every hour (or every 2 hours for antithrombin III) for 12 hours from 5 groups of 5 equids each after single injection of 40, 60, 80, 100, or 125 U of calcium heparin/kg of body weight and from 11 equids after injection of 150 U of calcium heparin/kg. The smaller dose ...
Colonic alpha 2-adrenoceptor-mediated responses in the pony. The motor responses of the caecum and colon to stimulation of alpha 2-adrenoceptors by xylazine and detomidine at the recommended dose levels of 0.6 and 0.1 mg/kg were investigated in three ponies. The motor changes of the left ventral colon induced by continuous intra-arterial infusion of a prostaglandin (PGF2 alpha) were used to assess the relative inhibitory effects of xylazine and detomidine in a colic model. The administration of alpha 2-agonists inhibited the spiking activity on the whole of the large intestine for 20-30 min (xylazine) or 2-3 h (detomidine). However, the detomidine-induc...
Pharmacological modulation of postprandial colonic motor activity in the pony. The contractile activity of the equine large intestine exhibited a biphasic response to feeding: enhancement of migrating complexes passing along the colon and an increase of 50% in cyclic variations in smooth muscle at intervals of 20 min on the left ventral colon for a period of 5 to 7 h postfeeding. The cholinergic agonist, bethanechol (50 micrograms/kg subcutaneously), induced both the migrating complexes and the cyclic variations at intervals of 10-15 min. In contrast, the intra-arterial infusion of PGF2 alpha (3 micrograms/kg/min) increased the contractile activity during infusion, but w...
Alpha- and beta-adrenergic receptors in the horse ureter. The presence of both alpha and beta adrenergic receptors in the caudal third ureter of the horse were studied in vitro under isometric conditions using adrenergic agonist and antagonist drugs. Isoprenaline and the beta 2- stimulating agent, salbutamol, elicited relaxation of the ureter smooth muscle strips. The responses were not affected by the beta 1- blocking agent, practolol, but were totally abolished by propranolol and the beta 2- blocking agent, butoxamine. The stimulation of alpha-adrenergic receptors with noradrenaline and phenylephrine evoked a contractile effect which was totally in...
Effects of physiologic and pharmacologic agents on serum prolactin concentrations in the nonpregnant mare. Four studies were conducted to evaluate the effects of several physiologic and pharmacologic agents on serum prolactin concentrations in the nonpregnant mare. An increase in prolactin measured in response to administration of thyrotropin-releasing hormone (TRH; 50 micrograms, iv) was found not to vary (P = .20) in mares in estrus compared with mares in diestrus (5 to 10 d post-ovulation). Administration in the dopamine receptor blocker, metoclopramide (25 or 100 mg, im), rapidly increased serum prolactin, and the response was dependent on dose administered (total prolactin measured for 420 min...
[Circulatory and respiratory effects of ketamine in horses anesthetized with halothane]. Ketamine (0.3 mg/kg) administered intravenously to 12 halothane anesthetized horses caused a significant respiratory depression during ten minutes when respiration was spontaneous. Significant hemodynamic effects were not observed except for cardiac index. Clinical application was also discussed. Ketamine (0.3 mg/kg) administered intravenously to 12 halothane anesthetized horses caused a significant respiratory depression during ten minutes when respiration was spontaneous. Significant hemodynamic effects were not observed except for cardiac index. Clinical application was also discussed.