Browsing by Author "Kongara, Kavitha"

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    Analgesic efficacy and pharmacokinetics of combinations of morphine, dexmedetomidine and maropitant in dogs : a thesis presented in partial fulfilment of the requirement for the degree of Doctor of Philosophy at Massey University, Palmerston North, New Zealand
    (Massey University, 2020) Karna, Sandeep Raj
    Multimodal analgesia is gaining popularity in veterinary medicine. It is an approach that involves the administration of two or three classes of analgesic drugs with different modes of actions to enhance the analgesic effects and lower the adverse effects associated with high dose of a single drug. In a series of experiments conducted in this thesis, the combinations of morphine, dexmedetomidine and maropitant were evaluated using different pain models with the aim of using them in a multimodal strategy in dogs undergoing ovariohysterectomy or other surgical procedures. Firstly, a pilot study evaluating the efficacy of combinations of the test drugs was performed using a hot-plate test and tail-flick test in rats. The combination of morphine and maropitant showed a significantly higher (p < 0.0001) tail-flick latency compared to all other treatment groups indicating a supra-additive effect of spinal analgesia between morphine and maropitant. A pharmacokinetic study to investigate the disposition of the test drug combinations after intramuscular (IM) administration in dogs under anaesthesia was conducted. The results showed that the elimination half-life of morphine was higher and the clearance rate was lower when combined with dexmedetomidine compared to morphine and maropitant combination or morphine alone at higher doses. This effect may have a clinical advantage of prolonging the dosing interval of morphine. A study to evaluate and compare the analgesic efficacy of the combination of morphine, dexmedetomidine and maropitant in dogs undergoing ovariohysterectomy was conducted. The study showed that dogs receiving the combination of morphine and dexmedetomidine had significantly lower (p < 0.05) pain scores, obtained by the short form of the Glasgow composite measure pain scale and visual analogue pain scale, in the postoperative period. All dogs that received dexmedetomidine showed arrhythmia and second-degree heart block immediately after IM administration. Finally, the efficacy of the test drug combinations was evaluated using changes in electroencephalographic indices of nociception (median frequency, spectral edge frequency and total power) in anaesthetised dogs subjected to a noxious electrical stimulus. The combination of morphine and dexmedetomidine showed a significantly lower change in the post stimulation median and spectral edge frequencies compared to all other treatment groups. The dogs receiving dexmedetomidine also demonstrated arrhythmia and second-degree heart block. In conclusion, the combination of morphine and dexmedetomidine showed a superior analgesic effect compared to morphine alone at higher dose and appeared to be the most effective combination among other combinations of morphine, dexmedetomidine and maropitant. The cardiovascular changes produced by the test drugs may be clinically insignificant in fit and healthy dogs. In future, the efficacy of the combination of morphine, dexmedetomidine and maropitant at other different doses rates and ratios should also be evaluated.
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    Studies on renal safety and preventive analgesic efficacy of tramadol and parecoxib in dogs : thesis in fulfilment of the degree of Doctor of Philosophy in Veterinary Clinical Science, Institute of Veterinary Animal and Biomedical Sciences, College of Sciences, Massey University, Palmerston North, New Zealand
    (Massey University, 2008) Kongara, Kavitha
    Ovariohysterectomy and castration are common surgical procedures in small animal practice that can result in clinically significant postoperative pain. One way of controlling postoperative pain is administration of a single analgesic or a combination of different classes of analgesics prior to the onset of noxious stimuli. A constraint to the perioperative use of traditional opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is their undesirable side effects. In this series of experiments, the preventive (pre-emptive) analgesic efficacy of two popular human analgesics, tramadol (an ?atypical? opioid) and parecoxib (a NSAID with selective COX-2 inhibition) was evaluated in dogs. Initially, the efficacy and renal safety of parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol (a -adrenoceptor blocker and 5-HT1A/1B antagonist) were screened in anaesthetised healthy dogs. These analgesics increased the dogs? nociceptive threshold to mechanical stimuli, without causing significant alterations in the dogs? glomerular filtration rate (GFR) estimated by plasma iohexol clearance. Subsequently, the efficacy of tramadol was compared with morphine, in dogs undergoing ovariohysterectomy or castration. The Glasgow composite measure pain scale-short form score (CMPS-SF) and changes in intraoperative electroencephalogram (EEG) responses were used to assess the efficacy of analgesics. Of the three treatment groups (preoperative morphine, 0.5 mg kg-1; preoperative tramadol, 3 mg kg-1; a ?combination? of preoperative low-dose morphine, 0.1 mg kg-1, and postoperative tramadol 3 mg kg-1), dogs given the ?combination? had significantly lower pain scores after ovariohysterectomy. In castrated dogs, preoperative tramadol (3 mg kg-1) and morphine (0.5 mg kg-1) were tested and no significant difference in the CMPS-SF score were observed between them. Changes in EEG variables were not specific between the treatment groups in ovariohysterectomised dogs. Finally, the efficacy of test drugs was evaluated against acute noxious electrical stimulation in anaesthetised dogs, using EEG. Median frequency of the EEG, a reliable indicator of nociception, increased significantly in tramadol and parecoxib groups, compared to morphine, after electrical stimulation. These studies demonstrated that tramadol and parecoxib can produce analgesia in dogs with insignificant side effects. The efficacy of tramadol appears to vary with the type of noxious stimulus. A complete prevention of noxious input by administration of analgesics pre- and post-operatively could have important clinical applications.