The Gastroduodenal Effects of Buffered Aspirin, Carprofen, and Etodolac in Healthy Dogs

Twenty-four healthy mixed-breed dogs were divided into 4 groups. Group 1 received a placebo p.o. q12h, group 2 received an average of 16.5 (15.1-17.8) mg/kg buffered aspirin p.o. q12h, group 3 received an average of 2.2 (2.0-2.4) mg/kg carprofen p.o. q12h, and group 4 received an average of 12.8 (11.7-13.8) mg/kg etodolac p.o. q24h (with a placebo in the PM). All treatments continued for 28 consecutive days. Gastroduodenal endoscopy was performed on days -9, 0, 5, 14, and 28. Multiple gastric biopsies were obtained endoscopically on day -9 to determine each dog's Helicobacter infection status. Four regions in the stomach and 1 region in the proximal duodenum were evaluated endoscopically, and each was assigned a score from 1 to 11. Scores for each region then were summed to give a total score for each endoscopic evaluation. Erosions and submucosal hemorrhages were seen in all dogs receiving aspirin. Only minor gastric lesions were observed in the carprofen, etodolac, and control groups. No adverse clinical signs were noted in any dog given any treatment. Median total score on days 0, 5, 14, and 28, respectively, were as follows: group 1: 5.0, 5.0, 5.0, 5.0; group 2: 5.0, 27.0, 26.0, 27.5; group 3: 5.0, 5.0, 6.0, 5.0, group 4: 5.0, 7.0, 5.0, 5.0. There was no significant difference among dogs receiving carprofen, etodolac, or placebo. The administration of carprofen, etodolac, or placebo to healthy dogs resulted in significantly less gastroduodenal lesion development than in dogs receiving buffered aspirin.     

Ivermectin缓控释制剂的研究进展

近年来 ,ivermectin(伊维菌素 ,IVM)缓、控释制剂广泛应用于动物寄生虫及多种疫病的防治 ,本文就其作用、制剂、优点、药物代谢动力学和可能带来的问题等方面进行了综述     

The coxib NSAIDs: potential clinical and pharmacologic importance in veterinary medicine

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to control acute and chronic pain as well as to manage oncologic and neurologic diseases in human and veterinary patients. Despite ongoing research and efforts to improve the safety and efficacy of existing drugs, adverse effects such as gastrointestinal irritation, renal and hepatic toxicity, interference with hemostasis, and reproductive problems persist. The true incidence of NSAID-induced adverse effects in animals is unknown, but is likely underestimated, because cats and dogs may be more sensitive than humans to NSAIDs due to alterations in drug metabolism, absorption, and enterohepatic recirculation. NSAIDs produce both analgesia and toxic adverse effects primarily by inhibiting cyclooxygenase (COX), thereby decreasing the production of prostaglandins that signal inflammation and pain as well as mediate physiologic functions such as platelet aggregation, gastric protection, and electrolyte balance in the kidney. The presence of at least 2 COX isoforms may account for variability in NSAID efficacy and toxicity both within and among species. This paper reviews and evaluates the published literature on the safety, pharmacology, uses, and complications of a subclass of COX-1-sparing drugs, the coxibs, in veterinary medicine. Coxibs and other COX-1-sparing drugs provide a clinically useful improvement over traditional NSAIDs, but data are incomplete and more in vivo species-specific, target-tissue, and clinical studies are needed.     

Pharmacopuncture Analgesia Using Flunixin Meglumine Injection into the Acupoint GV1 (Ho Hai) After Elective Castration in Horses

The study evaluated the effect of a 1/10 dose of flunixin meglumine administered into the governing vessel 1 (GV1) acupoint in horses that underwent castration. Twenty animals received 0.02 mg/kg detomidine intravenously, followed by 2.2 mg/kg ketamine and 0.1 mg/kg diazepam by the same route, and also a local anesthesia with 30 mL lidocaine. As postoperative analgesia, the animals received 1.1 mg/kg flunixin meglumine IV (FIV) or 0.11 mg/kg flunixin meglumine into the GV1 acupoint (FGV). Behavioral parameters were assessed 12 hours before the procedure (baseline) and at 4, 6, 12, and 24 hours after surgery; physiological parameters were measured at baseline and at 2, 4, 6, 8, 10, 12, 16, and 24 hours after surgery. The groups did not differ regarding pain scores. Heart rate was higher in the FIV group than in the FGV group 2 hours after surgery (46 ± 5.2 bpm vs. 37 ± 8.2 bpm); gut sounds decreased at 2, 4, and 6 hours in both groups. The temperature showed a decrease after 2 hours compared with baseline in the FGV group, and the systolic blood pressure was higher in the FGV group than in the FIV group at 8 hours (158 ± 18.1 mmHg vs. 134 ± 14.5 mmHg), 10 hours (157 ± 15.5 mm Hg vs. 130 ± 11.5 mmHg), and 12 hours (151 ± 18.7 mmHg vs. 134 ± 15.8 mmHg). Pharmacopuncture was as effective as conventional dose and route of flunixin meglumine in horses that underwent elective castration under those conditions.     

Cyclooxygenase-2 expression in canine appendicular osteosarcomas

Osteosarcoma is the most common primary bone tumor in dogs and it has a high mortality rate from distant metastatic disease. Targeted adjuvant therapies are needed to prolong currently achievable survival times. The role of cyclooxygenase-2 (COX-2) in carcinogenesis has been attributed to the production of prostaglandins and involvement in apoptosis, immune surveillance, and angiogenesis. COX-2 is up-regulated in a number of different human and animal epithelial tumors, but data about its function in mesenchymal tumors is lacking. The purpose of this study was to evaluate COX-2 expression in canine appendicular osteosarcomas and to identify if a relationship exists between the intensity of COX-2 expression and clinicopathologic outcome. Of 44 osteosarcomas analyzed, 34 (77.3%) were positive for COX-2 expression. Most of the positive cases (88%) had poor to moderate COX-2 staining. Dogs that had strong COX-2 expression had significantly decreased overall survival time (P = .0107). The median survival times for dogs with negative (n = 10), poor (n = 19), moderate (n = 11), and strong (n = 4) expression were 423, 399, 370, and 86 days, respectively. Additional studies are warranted to further evaluate COX-2 in osteosarcoma for its prognostic value and as a target for adjuvant therapy.     

Effects of deracoxib or buffered aspirin on the gastric mucosa of healthy dogs

BACKGROUND: Use of cyclo-oxygenase-2 specific nonsteroidal anti-inflammatory drugs such as deracoxib has been advocated because of their anti-inflammatory actions and apparently low incidence of gastrointestinal adverse effects. HYPOTHESIS: Deracoxib will cause less endoscopically detectable gastric injury in dogs than aspirin, a nonselective nonsteroidal anti-inflammatory drug. ANIMALS: Twenty-four random source healthy dogs. METHODS: A randomized, placebo-controlled trial compared gastroscopic findings of dogs receiving placebo (q8h), aspirin (25 mg/kg PO q8h), or deracoxib (1.5 mg/kg QD, placebo ql2h) for 28 days. Gastroscopy on days -7, 6, 14, and 28 evaluated 4 regions of the stomach separately and visible lesions were scored. Dogs were observed every 8 hours for vomiting and diarrhea. Median total scores for each group were compared each day of endoscopic examination and total dog-days of vomiting and diarrhea were compared. Significance was determined at P < .05. RESULTS: There were significant differences in total scores of the aspirin group and both the placebo and deracoxib groups on days 6, 14, and 28. No significant differences in total scores were found between placebo and deracoxib on days 6, 14, and 28. Significant differences in dog-days of vomiting were found between the aspirin and deracoxib groups whereas no significant differences were found between the deracoxib and placebo groups. There was no detectable effect of treatment on dog-days of diarrhea. CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of deracoxib to healthy dogs resulted in significantly lower gastric lesion scores, and fewer days of vomiting compared to aspirin, indicating that deracoxib is better tolerated than aspirin in some dogs.     

Bioavailability and Tolerability of Topical and Oral Diclofenac Sodium Administration in Healthy Ponies

Aiming to characterize the bioavailability and assess the safety of topical and oral treatment of diclofenac sodium in healthy ponies, 18 animals were divided in three groups: one treated with topical (group I, n = 6), the second with oral diclofenac (group II, n = 6) at 2.5 mg/kg for 3 days, and the third group received 2.2 mg/kg oral phenylbutazone (group III, n = 6) also for 3 days to serve as positive control. To evaluate bioavailability, blood samples were collected before and at 0, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours after starting treatment. To evaluate diclofenac sodium concentration in the synovial fluid, samples of six ponies (group I, n = 3; group II, n = 3) were collected at 6, 12, and 24 hours after starting the treatment.     

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.     

Pharmacokinetics and Safety of Oral Administration of Meloxicam to Foals

Background

The pharmacokinetics, efficacy, and safety of meloxicam have been evaluated in adult horses, but not foals. Physiologic differences between neonates and adults might alter drug pharmacokinetics and therapeutic index.

Hypotheses

The pharmacokinetics of meloxicam will be different in foals compared with adult horses, and foals could be at increased risk for adverse drug effects.

Animals

Twenty lightbreed foals less than 6 weeks of age at commencement of the study.

Methods

Single and repeated oral dose pharmacokinetics were determined for meloxicam (0.6 mg/kg) in 10 foals. The safety of the drug was further evaluated in a 2nd group of 10 foals in a randomized blinded prospective study.

Results

Plasma concentrations after a single oral dose of meloxicam (0.6 mg/kg) and time to maximum plasma concentration were similar to adult horses. However, drug clearance was much more rapid in foals (elimination half‐life 2.48 ± 0.25 hours). Administration of 0.6 mg/kg every 12 hours was well tolerated by foals for up to 3 weeks, with no evidence of drug accumulation in plasma. Adverse effects observed in adult horses at higher dose rates were not observed in foals given 1.8 mg/kg twice daily for 7 days.

Conclusions and clinical importance

Meloxicam at an oral dose rate of 0.6 mg/kg every 12 hours provided plasma concentrations likely to be therapeutic. In contrast to findings for other NSAIDs, foals appeared more resilient to the adverse effects of this drug than was observed in adult horses.     

Amantadine in a multimodal analgesic regimen for alleviation of refractory osteoarthritis pain in dogs

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) do not always provide sufficient pain relief in dogs with osteoarthritis (OA). HYPOTHESIS: The use of amantadine in addition to NSAID therapy will provide improved pain relief when compared with the use of nonsteroidal analgesics alone in naturally occurring OA in dogs. ANIMALS: Thirty-one client-owned dogs with pelvic limb lameness despite the administration of an NSAID. METHODS: The study was randomized, blinded, and placebo controlled with parallel groups (days 21-42). On day 0, analgesic medications were discontinued. On day 7, all dogs received meloxicam for 5 weeks. On day 21, all dogs received amantadine (3-5 mg/kg once daily per os) or placebo for 21 days, in addition to receiving meloxicam. Assessments were performed before the study and on days 7, 21, and 42. Primary outcome measures were blinded owner assessments of activity using client-specific outcome measures (CSOM) on days 0, 7, 21, and 42. Data were analyzed by a mixed model approach. RESULTS: For CSOM activity, there was a significant time by treatment effect (P=.009). On the basis of the planned post hoc t-tests of postrandomization means, there was a significant difference between treatment groups on day 42 (P=.030), with the amantadine group being more active. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with osteoarthritic pain refractory to an NSAID, physical activity is improved by the addition of amantadine. Amantadine might be a useful adjunct therapy for the clinical management of canine osteoarthritic pain.