Search Results

Abstract

Objective—To investigate the effects of oral administration of activated charcoal (AC) and urine alkalinization via oral administration of sodium bicarbonate on the pharmacokinetics of orally administered carprofen in dogs.

Animals—6 neutered male Beagles.

Procedures—Each dog underwent 3 experiments (6-week interval between experiments). The dogs received a single dose of carprofen (16 mg/kg) orally at the beginning of each experiment; after 30 minutes, sodium bicarbonate (40 mg/kg, PO), AC solution (2.5 g/kg, PO), or no other treatments were administered. Plasma concentrations of unchanged carprofen were determined via high-performance liquid chromatography at intervals until 48 hours after carprofen administration. Data were analyzed by use of a Student paired t test or Wilcoxon matched-pairs rank test.

Results—Compared with the control treatment, administration of AC decreased plasma carprofen concentrations (mean ± SD maximum concentration was 85.9 ± 11.9 mg/L and 58.1 ± 17.6 mg/L, and area under the time-concentration curve was 960 ± 233 mg/L•h and 373 ± 133 mg/L•h after control and AC treatment, respectively). The elimination half-life remained constant. Administration of sodium bicarbonate had no effect on plasma drug concentrations.

Conclusions and Clinical Relevance—After oral administration of carprofen in dogs, administration of AC effectively decreased maximum plasma carprofen concentration, compared with the control treatment, probably by decreasing carprofen absorption. Results suggest that AC can be used to reduce systemic carprofen absorption in dogs receiving an overdose of carprofen. Oral administration of 1 dose of sodium bicarbonate had no apparent impact on carprofen kinetics in dogs.

Abstract

Objective—To detect monocarboxylate transporters (MCTs) in canine RBC membranes and to determine the distribution of lactate between plasma and RBCs.

Sample population—Blood samples obtained from 6 purpose-bred Beagles.

Procedures—Monocarboxylate transporter isoforms 1, 2, 4, 6, 7, and 8 and CD147 were evaluated in canine RBCs by use of western blot analysis. Lactate influx into RBCs was measured as incorporation of radioactive lactate.

Results—2 MCT isoforms, MCT1 and MCT7, were detected in canine RBC membranes on western blot analysis, whereas anti-MCT2, anti-MCT4, anti-MCT6, and anti-MCT8 antibodies resulted in no signal. No correlation was found between the amount of MCT1 or MCT7 and lactate transport activity, but the ancillary protein CD147 that is needed for the activity of MCT1 had a positive linear correlation with the rate of lactate influx. The apparent Michaelis constant for the lactate influx in canine RBCs was 8.8 ± 0.9mM. Results of in vitro incubation studies revealed that at lactate concentrations of 5 to 15mM, equilibrium of lactate was rapidly obtained between plasma and RBCs.

Conclusions and Clinical Relevance—These results indicated that at least half of the lactate transport in canine RBCs occurs via MCT1, whereas MCT7 may be responsible for the rest, although an additional transporter was not ruled out. For practical purposes, the rapid equilibration of lactate between plasma and RBCs indicated that blood lactate concentrations may be estimated from plasma lactate concentrations.

Abstract

Objective—To determine whether a high dose of levomedetomidine had any pharmacologic activity or would antagonize the sedative and analgesic effects of dexmedetomidine in dogs.

Animals—6 healthy Beagles.

Procedure—Each dog received the following treatments on separate days: a low dose of levomedetomidine (10 µg/kg), IV, as a bolus, followed by continuous infusion at a dose of 25 µg/kg/h; a high dose of levomedetomidine (80 µg/kg), IV, as a bolus, followed by continuous infusion at a dose of 200 µg/kg/h; and a dose of isotonic saline (0.9% NaCl) solution, IV, as a bolus, followed by continuous infusion (control). For all 3 treatments, the infusion was continued for 120 minutes. After 60 minutes, a single dose of dexmedetomidine (10 µg/kg) was administered IV. Sedation and analgesia were scored subjectively, and heart rate, blood pressure, respiratory rate, arterial blood gas partial pressures, and rectal temperatures were monitored.

Results—Administration of levomedetomidine did not cause any behavioral changes. However, administration of the higher dose of levomedetomidine enhanced the bradycardia and reduced the sedative and analgesic effects associated with administration of dexmedetomidine.

Conclusion and Clinical Relevance—Results suggest that administration of dexmedetomidine alone may have some cardiovascular benefits over administration of medetomidine, which contains both dexmedetomidine and levomedetomidine. Further studies are needed to confirm the clinical importance of the effects of levomedetomidine in dogs. (Am J Vet Res 2001;62:616–621)

Abstract

Objective—To compare 3 dose levels of medetomidine and dexmedetomidine for use as premedicants in dogs undergoing propofol-isoflurane anesthesia.

Animals—6 healthy Beagles.

Procedure—Dogs received medetomidine or dexmedetomidine intravenously at the following dose levels: 0.4 µg of medetomidine or 0.2 µg of dexmedetomidine/kg of body weight (M0.4/D0.2), 4.0 µg of medetomidine or 2.0 µg of dexmedetomidine/ kg (M4/D2), and 40 µg of medetomidine or 20 µg of dexmedetomidine/kg (M40/D20). Sedation and analgesia were scored before induction. Anesthesia was induced with propofol and maintained with isoflurane. End-tidal isoflurane concentration, heart rate, and arterial blood pressures and gases were measured.

Results—Degrees of sedation and analgesia were significantly affected by dose level but not drug. Combined mean end-tidal isoflurane concentration for all dose levels was higher in dogs that received medetomidine, compared with dexmedetomidine. Recovery time was significantly prolonged in dogs treated at the M40/D20 dose level, compared with the other dose levels. After induction, blood pressure decreased below reference range and heart rate increased in dogs treated at the M0.4/D0.2 dose level, whereas blood pressure was preserved in dogs treated at the M40/D20 dose level. However, dogs in these latter groups developed profound bradycardia and mild metabolic acidosis during anesthesia. Treatment at the M4/D2 dose level resulted in more stable cardiovascular effects, compared with the other dose levels. In addition, PaCO₂ was similar among dose levels.

Conclusions and Clinical Relevance—Dexmedetomidine is at least as safe and effective as medetomidine for use as a premedicant in dogs undergoing propofol-isoflurane anesthesia. (Am J Vet Res 2001;62:1073–1080)

Abstract

Objective—To compare the effects of pretreatment with dexamethasone, physical stress (exercise), or both on sedation and plasma hormone and glucose concentrations in dogs treated with dexmedetomidine (DEX).

Animals—6 healthy purpose-bred Beagles.

Procedure—Dogs received 4 treatments each in a randomized order prior to IV administration of DEX (5 µg/kg). Pretreatments were as follows: (1) IV administration of saline (0.9% NaCl) solution and no exercise (control group); (2) IV administration of dexamethasone (0.05 mg/kg) and no exercise (DM group); (3) IV administration of saline solution and exercise (EX group; 15 minutes of trotting on a treadmill at a speed of 2 m/s); and 4) IV administration of dexamethasone and exercise (DM+EX group).

Results—Following DEX administration, all dogs had similar times to recumbency and sedation index values, irrespective of pretreatment with dexamethasone or exercise. Plasma catecholamine concentrations decreased after DEX administration. Compared with control group dogs, plasma cortisol concentrations were higher in EX-group dogs prior to DEX administration and lower in DM- and DM+EX-group dogs following DEX administration. Administration of DEX decreased plasma cortisol concentration in EX-group dogs only. Plasma glucose concentration was not influenced by exercise or dexamethasone administration but was lower than baseline concentrations at 30 minutes after DEX administration and returned to baseline values by 90 minutes. Heart and respiratory rates and rectal temperature increased during exercise. After DEX administration, these values decreased below baseline values. The decrease in heart rate was of shorter duration in dogs that underwent pretreatment with dexamethasone, exercise, or both than in control group dogs

Conclusions and Clinical Relevance—Pretreatment with dexamethasone, moderate physical stress (exercise), or both did not influence sedation or cause adverse effects in healthy dogs treated with DEX. (Am J Vet Res 2005;66:260–265)

Abstract

Objective—To evaluate perfusion of abdominal organs in healthy cats by use of contrastenhanced ultrasonography.

Animals—10 young healthy anesthetized cats.

Procedures—Contrast-enhanced ultrasonography of the liver, left kidney, pancreas, small intestine, and mesenteric lymph nodes was performed on anesthetized cats.

Results—Typical perfusion patterns were found for each of the studied organs. Differences in perfusion among organs were associated with specific physiologic features. The liver was enhanced gradually and had a more heterogeneous perfusion pattern because of its dual blood supply and close proximity to the diaphragm, compared with other organs. An obvious and significant difference in perfusion was detected between the renal cortex and medulla. No significant differences in perfusion were detected among the pancreas, small intestine, and mesenteric lymph nodes.

Conclusions and Clinical Relevance—Results indicated that contrast-enhanced ultrasonography can be used in cats to estimate organ perfusion as in other species. Observed differences in perfusion variables can be mostly explained by physiologic differences in vascularity. (Am J Vet Res 2010;71:1305–1311)

Abstract

OBJECTIVE To compare the effects of MK-467 and hyoscine butylbromide on detomidine hydrochloride–induced cardiorespiratory and gastrointestinal changes in horses.

ANIMALS 6 healthy adult horses.

PROCEDURES Horses received detomidine hydrochloride (20 μg/kg, IV), followed 10 minutes later by MK-467 hydrochloride (150 μg/kg; DET-MK), hyoscine butylbromide (0.2 mg/kg; DET-HYO), or saline (0.9% NaCl) solution (DET-S), IV, in a Latin square design. Heart rate, respiratory rate, rectal temperature, arterial and venous blood pressures, and cardiac output were measured; blood gases and arterial plasma drug concentrations were analyzed; selected cardiopulmonary variables were calculated; and sedation and gastrointestinal borborygmi were scored at predetermined time points. Differences among treatments or within treatments over time were analyzed statistically.

RESULTS With DET-MK, detomidine-induced hypertension and bradycardia were reversed shortly after MK-467 injection. Marked tachycardia and hypertension were observed with DET-HYO. Mean heart rate and mean arterial blood pressure differed significantly among all treatments from 15 to 35 and 15 to 40 minutes after detomidine injection, respectively. Cardiac output was greater with DET-MK and DET-HYO than with DET-S 15 minutes after detomidine injection, but left ventricular workload was significantly higher with DET-HYO. Borborygmus score, reduced with all treatments, was most rapidly restored with DET-MK. Sedation scores and pharmacokinetic parameters of detomidine did not differ between DET-S and DET-MK.

CONCLUSIONS AND CLINICAL RELEVANCE MK-467 reversed or attenuated cardiovascular and gastrointestinal effects of detomidine without notable adverse effects or alterations in detomidine-induced sedation in horses. Further research is needed to determine whether these advantages are found in clinical patients and to assess whether the drug influences analgesic effects of detomidine.

Abstract

OBJECTIVE To assess the possible impact of medetomidine on concentrations of alfaxalone in plasma, when coadministered as a constant rate infusion (CRI) to dogs, and to determine the possible impact of medetomidine on the cardiopulmonary effects of alfaxalone during CRI.

ANIMALS 8 healthy adult Beagles.

PROCEDURES 3 treatments were administered in a randomized crossover design as follows: 1 = saline (0.9% NaCl) solution injection, followed in 10 minutes by induction of anesthesia with alfaxalone (loading dose, 2.4 mg/kg; CRI, 3.6 mg/kg/h, for 60 minutes); 2 = medetomidine premedication (loading dose, 4.0 μg/kg; CRI, 4.0 μg/kg/h), followed by alfaxalone (as in treatment 1); and, 3 = medetomidine (as in treatment 2) and MK-467 (loading dose, 150 μg/kg; CRI, 120 μg/kg/h), followed by alfaxalone (as in treatment 1). The peripherally acting α₂-adrenoceptor antagonist MK-467 was used to distinguish between the peripheral and central effects of medetomidine. Drugs were administered IV via cephalic catheters, and there was a minimum of 14 days between treatments. Cardiopulmonary parameters were measured for 70 minutes, and jugular venous blood samples were collected until 130 minutes after premedication. Drug concentrations in plasma were analyzed with liquid chromatography–tandem mass spectrometry.

RESULTS The characteristic cardiovascular effects of medetomidine, such as bradycardia, hypertension, and reduction in cardiac index, were obtunded by MK-467. The concentrations of alfaxalone in plasma were significantly increased in the presence of medetomidine, indicative of impaired drug distribution and clearance. This was counteracted by MK-467.

CONCLUSIONS AND CLINICAL RELEVANCE The alteration in alfaxalone clearance when coadministered with medetomidine may be attributed to the systemic vasoconstrictive and bradycardic effects of the α₂-adrenoceptor agonist. This could be clinically important because the use of α₂-adrenoceptor agonists may increase the risk of adverse effects if standard doses of alfaxalone are used.

Abstract

Objective—To evaluate the adverse effects of carprofen in dogs after oral administration for 2 months.

Design—Prospective, randomized, blinded, placebo-controlled clinical trial.

Animals—22 dogs with osteoarthritis in the hip or elbow joint.

Procedure—13 dogs received orally administered carprofen daily for 2 months, and 9 dogs received a placebo for 2 months. Dogs were weighed, and serum and urine samples were collected before initiation of treatment and 4 and 8 weeks after initiation of treatment. Serum concentrations of total protein, albumin, urea, and creatinine and serum activities of alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were measured. Urinary ALP-to-creatinine, γ-glutamyltransferase (GGT)-to-creatinine, and protein-to-creatinine ratios were calculated. Dogs were observed by owners for adverse effects.

Results—Serum protein and albumin concentrations were lower in treated dogs than in those that received placebo at 4 weeks, but not at 8 weeks. No changes were observed in serum urea or creatinine concentrations; ALP or ALT activity; or urinary ALP-to-creatinine, GGT-to-creatinine, or protein-to-creatinine ratios. Dogs' weights did not change. Severity of vomiting, diarrhea, and skin reactions did not differ between groups, but appetite was better in dogs receiving carprofen than in dogs in the placebo group.

Conclusions and Clinical Relevance—It is possible that the transient decreases in serum protein and albumin concentrations in dogs that received carprofen were caused by altered mucosal permeability of the gastrointestinal tract because no indications of renal or hepatic toxicity were observed. Carprofen appeared to be well tolerated by dogs after 2 months of administration.

Abstract

Objective—To compare the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication.

Animals—42 client-owned dogs that underwent elective ovariohysterectomy.

Procedure—Each dog was randomly allocated to receive medetomidine and butorphanol tartrate (20 µg/kg and 0.2 mg/kg, respectively, IM) or acepromazine maleate and butorphanol (0.05 and 0.2 mg/kg, respectively, IM) for preanesthetic medication. Approximately 80 minutes later, anesthesia was induced by administration of propofol and maintained by use of isoflurane in oxygen. Each dog was also given carprofen before surgery and buprenorphine after surgery. Plasma concentrations of epinephrine, norepinephrine, cortisol, and β-endorphin were measured at various stages during the perioperative period. In addition, cardiovascular and clinical variables were monitored.

Results—Concentrations of epinephrine, norepinephrine, and cortisol were significantly lower for dogs administered medetomidine. Concentrations of β-endorphin did not differ between the 2 groups. Heart rate was significantly lower and mean arterial blood pressure significantly higher in dogs administered medetomidine, compared with values for dogs administered acepromazine.

Conclusions and Clinical Relevance—Results indicate that for preanesthetic medications, medetomidine may offer some advantages over acepromazine with respect to the ability to decrease perioperative concentrations of stress-related hormones. In particular, the ability to provide stable plasma catecholamine concentrations may help to attenuate perioperative activation of the sympathetic nervous system. (Am J Vet Res 2002;63:969–975)