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Pain Medications

Amantadine in a Multimodal Analgesic Regimen for Alleviation of Refractory Osteoarthritis Pain in Dogs

Summary:

“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.”

Conclusion:

“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.”

Author & Journal:Lascelles, B.D. et al, Journal of Veterinary Internal Medicine, 2008
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Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs

Summary:

“The objectives of this study were to determine basic oral pharmacokinetics, and assess safety and analgesic efficacy of a cannabidiol (CBD) based oil in dogs with osteoarthritis (OA).”

Conclusion:

“Pharmacokinetics revealed an elimination half-life of 4.2 h at both doses and no observable side effects. Clinically, canine brief pain inventory and Hudson activity scores showed a significant decrease in pain and increase in activity (p < 0.01) with CBD oil. Veterinary assessment showed decreased pain during CBD treatment (p < 0.02). No side effects were reported by owners, however, serum chemistry showed an increase in alkaline phosphatase during CBD treatment (p < 0.01).”

Author & Journal:Gamble, Lauri-Jo et al, Frontiers in Veterinary Science, 2018
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Pharmacokinetics of oral gabapentin in greyhound dogs.

Summary:

The purpose of this study was to assess the pharmacokinetics of gabapentin in healthy greyhound dogs after single oral doses targeted at 10 and 20mg/kg PO. Six healthy greyhounds were enrolled (3 males, 3 females).

Conclusion:

Gabapentin was rapidly absorbed and eliminated in dogs, indicating that frequent dosing is needed to maintain minimum targeted plasma concentrations.

Author & Journal:KuKanich B, et al, Vet J 2011;187:133-135
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Pharmacokinetics of tramadol and the metabolite O-desmethyltramadol in dogs.

Summary:

Tramadol is an analgesic and antitussive agent that is metabolized to O-desmethyltramadol (M1), which is also active. Tramadol and M1 exert their mode of action through complex interactions between opiate, adrenergic, and serotonin receptors. The pharmacokinetics of tramadol and M1 were examined following intravenous and oral tramadol administration to six healthy dogs, as well as intravenous M1 to three healthy dogs. The calculated parameters for half-life, volume of distribution, and total body clearance were 0.80 +/- 0.12 h, 3.79 +/- 0.93 L/kg, and 54.63 +/- 8.19 mL/kg/min following 4.4 mg/kg tramadol HCl administered intravenously. The systemic availability was 65 +/- 38% and half-life 1.71 +/- 0.12 h following tramadol 11 mg/kg p.o. M1 had a half-life of 1.69 +/- 0.45 and 2.18 +/- 0.55 h following intravenous and oral administration of tramadol. Following intravenous M1 administration the half-life, volume of distribution, and clearance of M1 were 0.94 +/- 0.09 h, 2.80 +/- 0.15 L/kg, and 34.93 +/- 5.53 mL/kg/min respectively. Simulated oral dosing regimens at 5 mg/kg every 6 h and 2.5 mg/kg every 4 h predict tramadol and M1 plasma concentrations consistent with analgesia in humans; however, studies are needed to establish the safety and efficacy of these doses.

Author & Journal:KuKanich B, et al, J Vet Pharmacol Therap 2004;27:239-246
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Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis.

Summary:

Pain and impaired mobility because of osteoarthritis (OA) is common in dogs and humans. Efficacy studies of analgesicdrug treatment of dogs with naturally occurring OA may be challenging, as a caregiver placebo effect is typically evident. However, little is known about effect sizes of common outcome-measures in canine clinical trials evaluating treatment of OA pain. Forty-nine client-owned dogs with hip OA were enrolled in a randomized, double-blinded placebo-controlled prospective trial. After a 1 week baseline period, dogs were randomly assigned to a treatment (ABT-116 – transient receptor potential vanilloid 1 (TRPV1) antagonist, Carprofen – non-steroidal anti-inflammatory drug (NSAID), Tramadol – synthetic opiate, or Placebo) for 2 weeks. Outcome-measures included physical examination parameters, owner questionnaire, activity monitoring, gait analysis, and use of rescue medication.

Conclusion:

Treatment of hip OA in client-owned dogs is associated with a placebo effect for all variables that are commonly used for efficacy studies of analgesic drugs. This likely reflects caregiver bias or the phenomenon of regression to the mean. In the present study, outcome measures with significant effects also varied between groups, highlighting the value of using multiple outcome measures, as well as an a priori analysis of effect size associated with each measure. Effect size data from the present study could be used to inform design of future trials studying analgesic treatment of canine OA. Our results suggest that analgesic treatment with ABT-116 is not as effective as carprofen or tramadol for treatment of hip arthritis pain in client-owned dogs.

Author & Journal:Malek S, et al, BMC Vet Research 2012;8:185
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Perforated peptic ulcer and short-term mortality among tramadol users.

Summary:

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is a strong risk and prognostic factor for peptic ulcer perforation, and alternative analgesics are needed for high-risk patients. * Pain management guidelines propose tramadol as a treatment option for mild-to-moderate pain in patients at high risk of gastrointestinal side-effects, including pepticulcer disease. * Tramadol may mask symptoms of peptic ulcer complications, yet tramadol’s effect on peptic ulcer prognosis is unknown.

WHAT THIS STUDY ADDS:  In this population-based study of 1271 patients hospitalized with peptic ulcer perforation, tramadol appeared to increase mortality at least as much as NSAIDs. * Among users of tramadol, alone or in combination with NSAIDs, adjusted 30-day mortality rate ratios were 2.02 [9

Conclusion:

Among patients hospitalized for perforated peptic ulcer, tramadol appears to increase mortality at a level comparable to NSAIDs.

Author & Journal:Torring ML, et al, Br J Clin Pharmacol 2007;65:565-572
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Lack of effectiveness of tramadol hydrochloride for the treatment of pain and joint dysfunction in dogs with chronic osteoarthritis.

Summary:

To investigate the effectiveness of tramadol for treatment of osteoarthritis in dogs.

Conclusion:

10 days of treatment with tramadol as administered (5 mg/kg, PO, q 8 h) provided no clinical benefit for dogs with osteoarthritis of the elbow or stifle joint.

Author & Journal:Budsberg SC, et al, J Am Vet Med Assoc 2018;252:427-432
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Pharmacokinetics and pharmacodynamics of oral acetaminophen in combination with codeine in healthy Greyhound dogs.

Summary:

The purpose of this study was to determine the pharmacokinetic and antinociceptive effects of an acetaminophen/codeine combinationadministered orally to six healthy greyhounds.

Conclusion:

Further studies using different models (including clinical trials), different dog breeds, multiple dose regimens, and a range of dosages are needed prior to recommended use or concluding lack of efficacy for oral acetaminophen/codeine in dogs.

Author & Journal:KuKanich B., J Vet Pharmacol Ther 2016;39:514-517
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Pharmacokinetics of intravenous and oral amitriptyline and its active metabolite nortriptyline in Greyhound dogs.

Summary:

To evaluate the pharmacokinetics of amitriptyline and its active metabolite nortriptyline after intravenous (IV) and oralamitriptyline administration in healthy dogs.

Conclusion:

Amitriptyline at 4 mg kg(-1) administered orally produced low amitriptyline and nortriptylineplasma concentrations. This brings into question whether the currently recommended oral dose of amitriptyline (1-4 mg kg(-1)) is appropriate in dogs.

Author & Journal:Norkus C, et al, Vet Anaesth Analeg 2015;42:580-589
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Clinical diagnosis and treatment of suspected neuropathic pain in three dogs.

Summary:

Three dogs were referred to The Queen’s Veterinary School Hospital at University of Cambridge for chronic behavioural or locomotor disorders associated with pain. All three had been unsuccessfully treated with conventional analgesics, including non-steroidal anti-inflammatory drugs, glucocorticoids and opiate agonists, prior to referral, with minimal or no response.

Conclusion:

Treatment with the tricyclic antidepressant drug, amitriptyline, or the antiepileptic drug, gabapentin, resulted in either a dramatic improvement or full resolution of clinical signs in all cases.

Author & Journal:Cashmore RG, et al, Aust Vet J 2009;87:45-50
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