Pharmacology of analgesic drugs in birds : thesis in fulfilment of the degree of Doctor of Philosophy in Animal Science

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Date
2011
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Massey University
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Abstract
Analgesics drugs are widely used to alleviate pain in mammals and birds. However, in the case of birds, there is a scarcity of information on their usage and dosing regimen. A lack of pharmacokinetic knowledge can result in under or over-dosing of drugs with subsequent loss of efficacy or side-effects. Complete understanding of a drug requires knowledge of its pharmacokinetics as well as pharmacodynamics. Considering the various voids in pharmacological research in birds and in an effort to know more about pain and welfare in birds, this study was designed to study the pharmacokinetics of morphine, butorphanol, aspirin and salicylic acid in broiler chickens. Broiler chickens were used as a model for wild and rare birds. Morphine and butorphanol were injected intravenously at 2 mg/kg, while aspirin and salicylic acid were injected intravenously at 50 mg/kg. All the analgesic drugs were well distributed in chickens. The plasma clearance for these drugs was much higher than in mammals, resulting in shorter half-lives. All the drugs remained within the theoretical therapeutic range for 2 hours. For analgesic efficacy testing, all the drugs except aspirin were injected in lame broiler chickens at similar dose rates as in the pharmacokinetics experiment. The results from the efficacy tests suggest that butorphanol and salicylic acid provided adequate analgesia which lasted for less than 2 hours. Morphine at 2 mg/kg intravenously induced sedation and drowsiness in chickens, which might be due to the high dose. It may have analgesic effects at lower dose rates, however this needs to be further evaluated. The approximate therapeutic range in broiler chickens for butorphanol is 50 to 80 ng/mL and for salicylic acid is 50 to 110 ng/mL. The therapeutic range for butorphanol is much higher in birds as compared to mammals while for salicylic acid it is in the mammalian range. The duration of analgesia in birds could be increased by using sustained released formulation or drug delivery systems, which warrants further research. Plasma concentrations after butorphanol given at 4 mg/kg in an injured Northern Royal Albatross under surgical conditions were also evaluated. This is the only pharmacokinetic study of an analgesic drug in a sea bird. The pharmacokinetics of butorphanol in this albatross differed significantly from chickens, with slower clearance and lower tissue distribution, although these were much higher than in mammals. The difference in pharmacokinetic parameters could either be due to species variation or due to the continuous fluid therapy along with butorphanol administration. This albatross was suffering from a major femur fracture, which potentially altered its normal physiology and metabolism. Chickens may be used as a model of drug research for wild and rare avian species, especially for preclinical trials. The dosing regimens can be extrapolated from chicken pharmacokinetics data, but this should be done with extreme caution as pharmacokinetics are highly variable between the species.
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Keywords
Analgesics, Pain in birds, Effects of drugs on birds, Broilers, Chickens, Morphine, Butorphanol, Aspirin, Salicylic acid, Albatross, Analgesia
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