Browsing by Subject "medetomidine"
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(University of HelsinkiHelsingin yliopistoHelsingfors universitet, 1993)In veterinary practice intraveneous anaesthesia has numerous advantages. An important advantage is the ease and rapidity of induction. Compared to administration of inhalant anaesthetics, a minimum of apparatus is necessary in administration of intraveneous anaesthetic agents. The possibility of antagonization of certain drugs used as intraveneous anaesthetics increases the safety of anaesthesia. The unpleasant recovery period can also be shortened, which for a busy veterinarian and also the owner can be of great relief. Ideally, a postoperative patient should be conscious, co-operative, calm and free of pain. This will provide better homeostasis of vital functions, allow early diagnosis and treatment of complications and decrease the need for nursing care. The aim of these studies was to analyze the sedative/ analgetic / anaesthetic, cardiovascular and respiratory effects produced by a combination of medetomidine and climazolam at two different dose levels (1.5 mg/kg and 3.0 mg/kg). Climazolam was also combined with fentanyl. Antagonization followed anaesthesia, using atipamezole, nalorphine and a new benzodiazepine antagonist, sarmazenil. 7 laboratory beagles were used inthis experimental study. In combination with medetomidine, climazolam produced smooth anaesthesia and had only small effects on the cardiovascular and respiratory system. Total analgesia was not achived. Intubation was easily performed. The antagonization proved to be fast and complete. When combining climazolam with fentanyl, dose levels were chosen according to previous studies (Erhardt et al., 1986). The anaesthesia was light and short, probably due to the short action of fentanyl. This combination depressed the respiratory system in a much larger scale than the combination of medetomidine and climazolam did. Antagonization was effective.
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(2011)Drug-drug interactions occur when a drug or a drug metabolite modifies the activity of a drug metabolizing enzyme. As a result the concentration of active drug can be too low to be effective or too high and possibly toxic. This is an increasing problem in drug therapy where polypharmacy is rather common today. Therefore, in drug discovery and development significant efforts have been made in order to predict such interactions in advance and avoid them, or at least minimize them. This study is focused on medetomidine, a drug metabolized by UDP-glucuronosyltransferases (UGT). The aim of the study was to find inhibitors for medetomidine glucuronidation. Also the mechanism of possible inhibition was of interest. It is already common to test interactions of a given enzyme substrate with other enzymes of the same family either in phase I or phase II of drug metabolism in humans. It is less common, however, to examine such interactions between enzymes of two different families. In the present study it is tested if the compounds which are possible inhibitors of cytochrome P450 monooxygenase (CYP) also inhibit UGTs. Inhibition of glucuronidation was studied with HPLC method previously developed for medetomidine glucuronidation. First glucuronidation of medetomidine was studied without inhibitor compounds. After that the impact of three possible inhibitors on medetomidine glucuronidation was studied and results were compared with the initial results. Three compounds were found to inhibit glucuronidation of medetomidine. Also an interesting change in UGT's enzyme kinetics after the binding of inhibitor was discovered. It is interesting that same compounds could inhibit both CYPs and UGTs. The results revealed that if a CYP and a UGT could bind for the same compound, it is also likely that structural analogues of that compound will interact with both enzymes. In drug discovery and development it is important to take into account both CYP-enzymes and less studied UGTs, and their possible interactions.
Now showing items 1-2 of 2