Effects of doxycycline, amoxicillin, cephalexin, and enrofloxacin on hemostasis in healthy dogs

OBJECTIVE: To determine the effects of enteral administration of doxycycline, amoxicillin, cephalexin, and enrofloxacin at therapeutic dosages for a typical duration on hemostatic variables in healthy dogs. ANIMALS: 14 Beagles. PROCEDURE: Doxycycline (10 mg/kg, PO, q 12 h), amoxicillin (30 mg/kg, PO, q 12 h), cephalexin (30 mg/kg, PO, q 12 h), and enrofloxacin (20 mg/kg, PO, q 24 h) were administered in random order to 10 healthy dogs at standard therapeutic dosages for 7 days, with a 7-day washout period between subsequent antimicrobials. In addition, 4 Beagles served as control dogs. Variables were evaluated before and after antimicrobial administration; they included platelet count, Hct, 1-stage prothrombin time (PT), activated partial thromboplastin time (PTT), fibrinogen concentration, and platelet function. Platelet function was assessed via buccal mucosal bleeding time, aggregation, and a platelet-function analyzer. RESULTS: Administration of all antimicrobials caused a slight prolongation of 1-stage PT and activated PTT and slight decrease in fibrinogen concentration. Cephalexin caused a significant increase in 1-stage PT and activated PTT, amoxicillin caused a significant increase in activated PTT, and enrofloxacin caused a significant decrease in fibrinogen concentration. Platelet count or function did not differ significantly after administration of any antimicrobial. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of commonly used antimicrobials in healthy dogs resulted in minor secondary hemostatic abnormalities, with no change in platelet count or function. Although these changes were clinically irrelevant in healthy dogs, additional studies of the effects of antimicrobial administration on hemostasis in animals with underlying disease processes are warranted.     

Effects of ranitidine, famotidine, pantoprazole, and omeprazole on intragastric pH in dogs

OBJECTIVE: To identify the normal gastric acid secretion profile in dogs and determine the degree of gastric acid suppression associated with 4 gastric acid suppressants. ANIMALS: 12 healthy Beagles. PROCEDURE: Intragastric pH was measured continuously for 24-hour periods with a digital recording system placed via a gastrostomy tube. Baseline measurements were obtained when food was withheld and when dogs were fed a standard diet. Dogs were then treated with ranitidine (2 mg/kg, IV, q 12 h), famotidine (0.5 mg/kg, IV, q 12 h), pantoprazole (1 mg/kg, IV, q 24 h), omeprazole (1 mg/kg, PO, q 24 h), or saline solution for 7 days; intragastric pH was recorded on days 0, 2, and 6. Subsequently, the effects of administering famotidine (0.5 mg/kg, IV, q 8 h; 6 dogs) and omeprazole as a suspension (1 mg/kg, PO, q 12 h; 6 dogs) were evaluated. Median 24-hour intragastric pH, percentage of time pH was > or = 3, and percentage of time pH was > or = 4 were determined. RESULTS: Median pH, percentage of time pH was > or = 3, and percentage of time pH was > or = 4 were all significantly higher when food was withheld than when dogs were fed. Famotidine, pantoprazole, and omeprazole significantly suppressed gastric acid secretion, compared with saline solution, as determined on the basis of median 24-hour pH and percentages of time pH was > or = 3 or > or = 4. However, ranitidine did not. Omeprazole suspension suppressed gastric acid secretion. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in healthy dogs, famotidine, pantoprazole, and omeprazole significantly suppress gastric acid secretion. Twice daily administration of a suspension of omeprazole, was the only regimen tested that approached the potential therapeutic efficacy for acid-related disease when assessed by criteria used for human patients.     

Effects of clomipramine hydrochloride on heart rate and rhythm in healthy dogs

OBJECTIVE: To determine the effects of clomipramine hydrochloride on heart rate and rhythm in dogs. ANIMALS: 17 healthy Beagles. PROCEDURES: In experiment 1, 8 dogs received placebo or clomipramine (20 mg/kg of body weight, q 24 h, PO) for 7 days in a 2-way crossover design. In experiment 2, 9 dogs were evaluated for 48 hours before and 24 hours after oral administration of clomipramine (4 or 12 mg/kg) in a 2-way crossover design. Electrocardiogram and heart rate were monitored continuously by use of telemetry. RESULTS: A significant diurnal rhythm in heart rate was detected; minimum values were recorded at night. Administration of 20 mg of clomipramine/kg induced a significant reduction in heart rate, with peak effect achieved approximately 12 hours after dosing. Administration of 4 or 12 mg of clomipramine/kg did not result in significant changes in heart rate. Sinoatrial and second-degree atrioventricular block and ventricular escape beats were observed during periods of slow heart rate in more dogs that received clomipramine (3 to 4 of 8 dogs), compared with dogs that received placebo (1 to 2 of 8 dogs), but this difference was not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Short-term administration of clomipramine induced benign cardiovascular effects in dogs rather than the potentially dangerous arrhythmias or tachycardia reported following administration of tricyclic antidepressants to humans. Precautions regarding cardiovascular effects may not be needed for the use of clomipramine in healthy dogs.     

Pharmacodynamics of carvedilol in conscious, healthy dogs

The purpose of the study reported here was to determine the magnitude and duration of beta-blocking efficacy, determine an effective dose and dosing interval, and document safety and tolerability of carvedilol given orally in clinically normal dogs. Pharmacodynamic data were evaluated in conscious, unrestrained, healthy hound dogs at baseline and after long-term oral administration of carvedilol (1.5 mg/kg of body weight PO q12h for >5 days). At baseline, heart rate (HR) and blood pressure (BP) data were collected continuously for 24 hours, and complete echocardiography was performed. This protocol was repeated after long-term oral carvedilol administration. Additionally, isoproterenol was administered to evaluate the magnitude and duration of the nonselective beta-blocking efficacy of carvedilol. An isoproterenol challenge was performed 0.75, 1.5, 2.25, 4, 6, 12, and 24 hours after carvedilol administration, with echocardiography being performed once at 2 hours. Plasma samples were obtained prior to each challenge time point for determination of plasma carvedilol concentration. Time series regression analysis indicated no difference between baseline and carvedilol-induced HR or BP trend lines in 6 of 8 dogs. In 2 of 8 dogs, HR, after long-term carvedilol administration, was reduced. Carvedilol attenuated isoproterenol-induced changes in HR by 54-76% through 12 hours and by 30% at 24 hours. The BP changes were attenuated by 80-100% through 12 hours. These data suggest that carvedilol (1.5 mg/kg PO q12h) in healthy, conscious dogs confers nonselective beta blockade for 12 hours, with minimal effects on resting HR, BP, and echocardiographic variables. Additionally, the magnitude of beta blockade correlated strongly to peak plasma carvedilol concentration, suggesting that therapeutic drug monitoring may be clinically useful.     

The effect of dosing interval on the efficacy of misoprostol in the prevention of aspirin-induced gastric injury

The effect of twice-daily administration of misoprostol on aspirin-induced gastric injury was evaluated. Twenty-four random-source dogs were divided into groups that received aspirin and misoprostol as follows: group I, aspirin 25 mg/kg PO q8h and placebo PO q8h; group II, aspirin 25 mg/kg PO q8h and misoprostol 3 microg/kg PO q8h; group III, aspirin 25 mg/kg PO q8h, misoprostol 3 microg/kg PO q12h, and placebo PO q24h; and group IV, aspirin 25 mg/kg PO q8h, misoprostol 3 microg/kg PO q24h, and placebo PO q12h for 28 days. Gastroscopy was performed on days -9, 5, 14, and 28. Visible lesions were scored on a scale of 1 (mucosal hemorrhage) to 11 (perforating ulcer). No difference in total score was identified between groups I and IV on any day. Median total scores for groups II and III were significantly (P < or = .05) lower compared to groups I and IV on day 5. Group III had a significantly lower score (P < or = .05) than groups I, II, and IV on day 28. This study suggests that misoprostol 3 microg/kg PO q12h is as effective as misoprostol 3 microg/kg PO q8h in preventing aspirin-induced gastric injury in this model. However, misoprostol 3 microg/ kg PO q8h was less effective in preventing aspirin-induced gastric injury on days 14 and 28 than in previous studies. No difference among numbers of dog-days of vomiting, diarrhea, or anorexia was detected among groups.     

Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism

OBJECTIVE: To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). DESIGN: Prospective study. ANIMALS: 28 dogs with NOH. PROCEDURES: 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. RESULTS: After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.     

Effect of cimetidine on pharmacokinetics of orally administered cyclosporine in healthy dogs.

OBJECTIVE: To describe the pharmacokinetics of cyclosporine (CyA) in healthy dogs after oral administration alone or in combination with orally administered cimetidine. ANIMALS: 10 healthy adult Beagles. PROCEDURE: Dogs were randomly assigned to receive CyA alone or CyA in combination with cimetidine. After a washout period of 2 weeks, dogs then received the alternate treatment. The CyA plus cimetidine treatment required administration of cimetidine (15 mg/kg of body weight, PO, q 8 h) for 8 days and administration of CyA (5 mg/kg, PO, q 24 h) on days 6 through 8. The CyA treatment alone required administration of CyA (5 mg/kg, PO, q 24 h) for 3 days. On the third day of CyA administration during each treatment, blood samples were collected immediately before (time 0) and 0.5, 1, 1.5, 2, 2.5, 3, 5, 7, 9, 11, 13, 15, 21, and 24 hours after initiating CyA administration. RESULTS: Time until maximum CyA concentration was significantly longer for CyA in combination with cimetidine. Assessment of estimated pharmacokinetic variables revealed a significantly faster rate of change in the distribution phase for CyA in combination with cimetidine. Maximum CyA concentration differed significantly among dogs but did not differ significantly between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of our data suggests that cimetidine may affect absorption of orally administered CyA, but overall, it does not affect the pharmacokinetics of CyA. There is considerable variability in the maximum concentration of CyA among dogs, and monitoring of blood concentrations of CyA during treatment is advised.     

Effects of administration of glucocorticoids and feeding status on plasma leptin concentrations in dogs

OBJECTIVE: To investigate effects of short- and long- term administration of glucocorticoids, feeding status, and serum concentrations of insulin and cortisol on plasma leptin concentrations in dogs. ANIMALS: 20 nonobese dogs. PROCEDURE: For experiment 1, plasma leptin concentrations and serum concentrations of insulin and cortisol were monitored for 24 hours in 4 dogs administered dexamethasone (0.1 mg/kg, IV) or saline (0.9% NaCl) solution for fed and nonfed conditions. For experiment 2, 11 dogs were administered prednisolone (1 mg/kg, PO, q 24 h for 56 days [7 dogs] and 2 mg/kg, PO, q 24 h for 28 days [4 dogs]) and 5 dogs served as control dogs. Plasma leptin and serum insulin concentrations were monitored weekly. RESULTS: For experiment 1, dexamethasone injection with the fed condition drastically increased plasma leptin concentrations. Furthermore, injection of saline solution with the fed condition increased plasma leptin concentrations. These increases in plasma leptin concentrations correlated with increases in serum insulin concentrations. Dexamethasone injection with the nonfed condition increased plasma leptin concentrations slightly but continuously. Injection of saline solution with the nonfed condition did not alter plasma leptin concentrations. For experiment 2, prednisolone administration at either dosage and duration did not alter plasma leptin concentrations in any dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Dexamethasone injection and feeding increased plasma leptin concentrations in dogs. In addition, dexamethasone administration enhanced the effect of feeding on increases in plasma leptin concentrations. Daily oral administration of prednisolone (1 or 2 mg/kg) did not affect plasma leptin concentrations in dogs.     

Efficacy of misoprostol in prevention of gastric hemorrhage in dogs treated with high doses of methylprednisolone sodium succinate.

OBJECTIVE: To determine whether administration of misoprostol prevents gastric hemorrhage in healthy dogs treated with high doses of methylprednisolone sodium succinate (MPSS). ANIMALS: 18 healthy hound-type dogs of both sexes. PROCEDURE: All dogs were given high doses of MPSS (30 mg/kg of body weight, initially, then 15 mg/kg 2 and 6 hours later, and, subsequently, q 6 h for a total of 48 hours) IV. Dogs were assigned randomly to receive concurrent treatment with misoprostol (4 to 6 microg/kg, PO, q 8 h; n = 9) or an empty gelatin capsule (9). Gastroduodenoscopy was performed before and after treatment. Hemorrhage was graded from none (0) to severe (3) for each cardia, fundus, antrum, and duodenum. A total stomach score was calculated as the sum of the regional stomach scores. Food retention was recorded, and pH of gastric fluid was determined. Gastric and fecal occult blood was measured. RESULTS: Gastric hemorrhage was evident in all dogs after MPSS administration, and its severity was similar in both groups. Median total stomach score was 6 for misoprostol-treated dogs and 5.5 for dogs given the gelatin capsule. Difference in gastric acidity, frequency of food retention, and incidence of occult blood in gastric fluid and feces was not apparent between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of misoprostol (4 to 6 microg/kg, PO, q 8 h) does not prevent gastric hemorrhage caused by high doses of MPSS. Alternative prophylactic treatment should be considered.     

Use of force plate analysis to assess the analgesic effects of etodolac in horses with navicular syndrome

OBJECTIVE: To evaluate the musculoskeletal analgesic effect of etodolac administered PO every 12 or 24 hours in chronically lame horses by use of force plate analysis. ANIMALS: 22 horses with navicular syndrome. PROCEDURE: Horses received etodolac (23 mg/kg, PO, q 12 h; n = 7), etodolac (23 mg/kg, PO, q 24 h; 8), or corn syrup (20 mL, PO, q 24 h; control treatment; 7) for 3 days. Combined forelimb peak vertical ground reaction force (PVF) was measured via force plate analysis before the first treatment (baseline) and at 6, 12, 24, and 36 hours after the last treatment. Differences in mean PVF (mPVF) between baseline and subsequent measurements were analyzed (repeated-measures ANOVA) and evaluated for treatment and time effects and treatment-time interaction. RESULTS: Once- or twice-daily administration of etodolac resulted in significant increases in mPVF from baseline at 6, 12, and 24 hours after the last treatment, compared with the control treatment. There were no significant differences in mPVF between the etodolac treatment groups at any time point. In both etodolac treatment groups, there was a significant increase in mPVF from baseline at 6, 12, and 24 hours, compared with that at 36 hours. Etodolac-associated adverse effects were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with navicular syndrome, once-daily oral administration of 23 mg of etodolac/kg appears to provide effective analgesia for as long as 24 hours. Twice-daily administration of etodolac at this same dose does not appear to provide any additional analgesic efficacy or duration of effect.     

Effects of deracoxib and aspirin on serum concentrations of thyroxine, 3,5,3'-triiodothyronine, free thyroxine, and thyroid-stimulating hormone in healthy dogs

OBJECTIVE: To evaluate the effects of deracoxib and aspirin on serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy dogs. ANIMALS: 24 dogs. PROCEDURE: Dogs were allocated to 1 of 3 groups of 8 dogs each. Dogs received the vehicle used for deracoxib tablets (PO, q 8 h; placebo), aspirin (23 to 25 mg/kg, PO, q 8 h), or deracoxib (1.25 to 1.8 mg/kg, PO, q 24 h) and placebo (PO, q 8 h) for 28 days. Measurement of serum concentrations of T4, T3, fT4, and TSH were performed 7 days before treatment (day -7), on days 14 and 28 of treatment, and 14 days after treatment was discontinued. Plasma total protein, albumin, and globulin concentrations were measured on days -7 and 28. RESULTS: Mean serum T4, fT4, and T3 concentrations decreased significantly from baseline on days 14 and 28 of treatment in dogs receiving aspirin, compared with those receiving placebo. Mean plasma total protein, albumin, and globulin concentrations on day 28 decreased significantly in dogs receiving aspirin, compared with those receiving placebo. Fourteen days after administration of aspirin was stopped, differences in hormone concentrations were no longer significant. Differences in serum TSH or the free fraction of T4 were not detected at any time. No significant difference in any of the analytes was detected at any time in dogs treated with deracoxib. CONCLUSIONS AND CLINICAL RELEVANCE: Aspirin had substantial suppressive effects on thyroid hormone concentrations in dogs. Treatment with high dosages of aspirin, but not deracoxib, should be discontinued prior to evaluation of thyroid function.     

Use of clomipramine,alprazolam, and behavior modification for treatment of storm phobia in dogs

OBJECTIVE: To evaluate use of clomipramine, alprazolam, and behavior modification for treatment of storm phobia in dogs. DESIGN: Prospective open clinical trial. ANIMALS: 40 dogs with storm phobia. PROCEDURE: Dogs received clomipramine at a dosage of 2 mg/kg (0.9 mg/lb), PO, every 12 hours for 3 months; then 1 mg/kg (0.45 mg/lb), PO, every 12 hours for 2 weeks; then 0.5 mg/kg (0.23 mg/lb), PO, every 12 hours for 2 weeks. Alprazolam was given at a dosage of 0.02 mg/kg (0.009 mg/lb), PO, as needed 1 hour before anticipated storms and every 4 hours as needed. Desensitization and counter-conditioning were conducted at home by the caregiver with an audio simulation of storm sounds that had induced a fear response during evaluation. RESULTS: 30 of the 32 dogs that completed the study had a degree of improvement, as measured by caregivers' global assessment. Two caregivers considered the storm phobia to be resolved. Panting, pacing, trembling, remaining near the caregiver, hiding, excessive salivation, destructiveness, excessive vocalization, self-trauma, and inappropriate elimination all decreased significantly during treatment. Improvement was greater during true storms (rain, thunder, and lightning) than during rain only. Response to audio simulation did not change during treatment. Four months after the study, improvement was maintained. CONCLUSIONS AND CLINICAL RELEVANCE: The combination of clomipramine, alprazolam, and behavior modification can be effective in decreasing or eliminating storm phobia. Improvement could not be evaluated by use of audio simulation of a storm.     

Serum concentrations of acute-phase proteins in dogs with leishmaniosis during short-term treatment

OBJECTIVE: To evaluate changes in serum concentrations of acute-phase proteins in dogs with leishmaniosis during short-term therapy in accordance with 2 treatment protocols and determine whether concentrations of acute-phase proteins could be used to monitor the initial response of dogs to treatment. ANIMALS: 12 dogs naturally infected with Leishmania infantum. PROCEDURE: Dogs were allocated into 2 groups. Dogs of group 1 were treated by use of meglumine antimonate (100 mg/kg, SC, q 24 h) administered concurrently with allopurinol (15 mg/kg, PO, q 12 h) for 20 days and then with allopurinol alone at the same dosage for the subsequent 30 days. Dogs of group 2 were treated by administration of allopurinol alone (15 mg/kg, PO, q 12 h) for 60 days). Blood samples were obtained before and during treatment for measurement of serum concentrations of acute-phase proteins and determination of CBC counts, serum biochemical analyses, and electropherograms. RESULTS: All dogs evaluated in the study had increased concentrations of C-reactive protein, haptoglobin, and ceruloplasmin at the time of diagnosis of leishmaniosis. Mean concentration of serum amyloid A before treatment was also increased, but some of the dogs had concentrations of serum amyloid A that were within the reference range. Concentrations of C-reactive protein and ceruloplasmin decreased significantly in all dogs at the end of the study period. CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of concentrations of selected acute-phase proteins, such as C-reactive protein or ceruloplasmin, could be used to evaluate the initial response of dogs with leishmaniosis to treatment.     

Pharmacokinetics of pentoxifylline in dogs after oral and intravenous administration

OBJECTIVE: To evaluate the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl-metabolite, metabolite 1 (M1), in dogs after IV administration of a single dose and oral administration of multiple doses. ANIMALS: 7 sexually intact, female, mixed-breed dogs. PROCEDURE: A crossover study design was used so that each of the dogs received all treatments in random order. A drug-free period of 5 days was allowed between treatments. Treatments included IV administration of a single dose of PTX (15 mg/kg of body weight), oral administration of PTX with food at a dosage of 15 mg/kg (q 8 h) for 5 days, and oral administration of PTX without food at a dosage of 15 mg/kg (q 8 h) for 5 days. Blood samples were taken at 0.25, 0.5, 1, 1.5, 2, 2.5, and 3 hours after the first and last dose of PTX was administered PO, and at 5, 10, 20, 40, 80, and 160 minutes after PTX was administered IV. RESULTS: PTX was rapidly absorbed and eliminated after oral administration. Mean bioavailability after oral administration ranged from 15 to 32% among treatment groups and was not affected by the presence of food. Higher plasma PTX concentrations and apparent bioavailability were observed after oral administration of the first dose, compared with the last dose during the 5-day treatment regimens. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, oral administration of 15 mg of PTX/kg results in plasma concentrations similar to those produced by therapeutic doses in humans, and a three-times-a-day dosing regimen is the most appropriate.     

Effects of selegiline,phenylpropanolamine, or a combination of both on physiologic and behavioral variables in healthy dogs

OBJECTIVE: To determine effects of selegiline hydrochloride, phenylpropanolamine (PPA), or a combination of both on physiologic and behavioral variables in dogs. ANIMALS: 40 adult hound-type dogs. PROCEDURE: Dogs were assigned to 4 groups. One group received selegiline (1 mg/kg, PO, q 24 h) and PPA (1.1 mg/kg, PO, q 8 h), a second group received selegiline alone, a third group received PPA alone, and a fourth group received neither drug. Dogs were observed 3 times/d throughout the 30-day study (daily during the first week, on alternate days during the next 2 weeks, and again daily during the final week). Observers recorded rectal temperature, pulse, respiratory rate, oscillometric blood pressure, and lead-II ECG and assessed 4 behaviors, using an analogue scale. Variables were compared among treatment groups by use of a 2-factor ANOVA with data categorized into three 10-day treatment periods. A similar comparison was made among treatment groups with data categorized by time of observation (morning, afternoon, or evening) for all study days. RESULTS: Variables did not differ among groups at study initiation. Pulse rate was the only variable that differed significantly among treatment groups during the study. During the first 10 days of treatment, dogs receiving PPA had a lower pulse rate than dogs that did not. Although signs of illness were apparent in a few dogs, illness did not appear to be related to treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Adverse effects were not detected after administration of selegiline, PPA, or a combination of the drugs in healthy dogs.     

Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs

OBJECTIVE: To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs. ANIMALS: 8 client-owned dogs with clinical signs of osteoarthritis. PROCEDURES: Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E(2), platelet thromboxane B(2) (TXB(2)), and free serum TXB(2) and 6-keto-prostaglandin F (PGF)-1alpha concentrations. RESULTS: Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and alpha-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E(2) decreased after treatment with carprofen or deracoxib, and platelet TXB(2) production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1alpha did not change significantly after treatment with any of the drugs, although the ratio of free TXB(2) to 6-keto-PGF-1alpha decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib. CONCLUSIONS AND CLINICAL RELEVANCE: At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.     

Comparison of pulse administration versus once daily administration of itraconazole for the treatment of Malassezia pachydermatis dermatitis and otitis in dogs

OBJECTIVE To compare clinical efficacy of pulse administration with itraconazole versus once daily administration for the treatment of cutaneous and otic M pachydermatis infection in dogs. DESIGN: Randomized controlled trial. ANIMALS: 20 dogs. PROCEDURE: Dogs were treated with itraconazole orally (n = 10/group), using a pulse administration regimen (5 mg/kg [2.3 mg/lb], PO, q 24 h for 2 consecutive days per week for 3 weeks) or once daily administration (5 mg/kg, PO, q 24 h for 21 days). No other treatment was permitted. On days 0 and 21, clinical severity of cutaneous and otic disease was assessed, and samples were collected for cytologic examination and yeast culture. Cytology (sum of the mean number of yeast organisms per oil immersion field for affected sites) and culture (mean of the score for extent of yeast growth for samples from affected sites) scores were calculated. RESULTS: For dogs in both treatment groups, clinical severity of cutaneous and otic disease was significantly decreased by day 21, but decrease in severity was not significantly different between groups. Similarly, skin cytology, skin culture, and ear culture scores were significantly decreased on day 21, compared with day 0, for both groups, but decreases were not significantly different between groups except that dogs in the pulse administration group had a significantly greater decrease in ear culture scores than did dogs in the daily administration group. However, when cytology scores only for ear samples were analyzed, day 21 score was not significantly decreased, compared with day 0 score, for either group. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that both pulse administration and once daily administration of itraconazole were efficacious in the treatment of M pachydermatis cutaneous infection in dogs. However, adjunctive treatment may be needed in dogs with M pachydermatis otitis.     

Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy

BACKGROUND: Despite traditional therapy of a diuretic, angiotensin converting enzyme inhibitor, digoxin, or a combination of these drugs, survival of dogs with dilated cardiomyopathy (DCM) is low. Pimobendan, an inodilator, has both inotropic and balanced peripheral vasodilatory properties. HYPOTHESIS: Pimobendan when added to conventional therapy will improve morbidity and reduce case fatality rate in Doberman Pinschers with congestive heart failure (CHF) caused by DCM. ANIMALS: Sixteen Doberman Pinschers in CHF caused by DCM. METHODS: A prospective randomized, double-blind, placebo-controlled study with treatment failure as the primary and quality of life (QoL) indices as secondary outcome variables. Therapy consisted of furosemide (per os [PO] as required) and benazepril hydrochloride (0.5 mg/kg PO q12h) and dogs were randomized in pairs and by sex to receive pimobendan (0.25 mg/kg PO q12h) or placebo (1 tablet PO q12h). RESULTS: Pimobendan-treated dogs had a significant improvement in time to treatment failure (pimobendan median, 130.5 days; placebo median, 14 days; P= .002; risk ratio = 0.35, P= .003, lower 5% confidence limit = 0.13, upper 95% confidence limit = 0.71). Number and rate of dogs reaching treatment failure in the placebo group precluded the analysis of QoL. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan should be used as a first-line therapeutic in Doberman Pinschers for the treatment of CHF caused by DCM.     

Effects of short-term trimethoprim-sulfamethoxazole administration on thyroid function in dogs

OBJECTIVE: To determine how rapidly trimethoprim-sulfamethoxazole affects serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in euthyroid dogs and how quickly hormone concentrations return to reference values following discontinuation of administration. DESIGN: Prospective study. ANIMALS: 7 healthy euthyroid dogs. PROCEDURE: Dogs were given trimethoprim-sulfamethoxazole (26.5 to 31.3 mg/kg [12 to 14.2 mg/lb], PO, q 12 h) for a maximum of 6 weeks. A CBC and Schirmer tear test were performed and serum total T4 and TSH concentrations were measured weekly. Administration of trimethoprim-sulfamethoxazole was discontinued if total T4 concentration was less than the lower reference limit and TSH concentration was greater than the upper reference limit or if persistent neutropenia developed. RESULTS: Six dogs had total T4 concentrations less than the lower reference limit within 3 weeks; T4 concentration was decreased after 1 week in 3 of these 6 dogs. In these 6 dogs, TSH concentration was greater than the upper reference limit within 4 weeks. In 1 dog, T4 and TSH concentrations were not affected, despite administration of trimethoprim-sulfamethoxazole for 6 weeks. Neutropenia developed in 4 dogs. In 1 dog, the neutropenia resolved while trimethoprim-sulfamethoxazole was still being administered. In the other 3, neutrophil counts returned to reference values 1 week after drug administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of trimethoprim-sulfamethoxazole at a dosage of 26.5 to 31.3 mg/kg, PO, every 12 hours can substantially alter serum total T4 and TSH concentrations and neutrophil counts in dogs within as short a time as a few weeks.     

Effect of oral melatonin administration on sex hormone, prolactin, and thyroid hormone concentrations in adult dogs.

OBJECTIVE: To determine the effect of oral melatonin (MT) administration on serum concentrations of sex hormones, prolactin, and thyroxine in dogs. DESIGN: Prospective study. ANIMALS: 8 male and 8 female adult sexually intact dogs. PROCEDURE: 5 male and 5 female dogs were treated with MT (1.0 to 1.3 mg/kg [0.45 to 0.59 mg/lb] of body weight), PO, every 12 hours for 28 days; the other 6 dogs were used as controls. Blood samples were collected on days 0, 14, and 28, and serum concentrations of estradiol-17 beta, progesterone, testosterone, androstenedione, 17-hydroxyprogesterone (17-HP), dihydroepiandrostenedione sulfate (DHEAS), prolactin, and thyroxine were determined. On day 5, serum MT concentrations were measured before and periodically for up to 8 hours after MT administration in 4 treated dogs. RESULTS: Female dogs treated with MT had significant decreases in serum estradiol, testosterone, and DHEAS concentrations between days 0 and 28. Male dogs treated with MT had significant decreases in serum estradiol and 17-HP concentrations between days 0 and 28. Serum MT concentrations increased significantly after MT administration and remained high for at least 8 hours. Prolactin and thyroxine concentrations were unaffected by treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Melatonin is well absorbed following oral administration and may alter serum sex hormone concentrations.