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Evaluation of the analgesic effects and pharmacokinetics of tramadol in red-footed tortoises

Grant number: 16/15776-2
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): October 01, 2016
Effective date (End): March 31, 2018
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
Principal Investigator:Silvia Renata Gaido Cortopassi
Grantee:Vanessa Nadine Gris
Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Brazil is home to one of the richest biodiversities in the world, ranking third in the total number of reptiles (791), behind only Australia (1038) and Mexico (910). Among them is the red-footed tortoise (Chelonoidis carbonarius), a common chelonian in Brazilian forests that became popular as a pet and have important representation in zoos and research facilities. Exotic animal veterinarians have been prescribing analgesics for their patients for many years, but recently the recognition and alleviation of pain in these patients have become widely recognized as an essential component of clinical veterinary care. All vertebrates possess the neuroanatomic and neuropharmacologic components necessary for the transduction, transmission, and perception of noxious stimuli. Also, the recognition of pain in reptiles is complex and can be even more difficult to determine objectively when an analgesic medication is effective for the patient. Therefore,it stands to reason the importance of research regarding pain processes experienced by these animals. In a survey with practioners of the Association of Reptilian and Amphibian Veterinarians, the most commom opioid analgesic administered in reptiles was butorphanol with dosages ranging from 0.02 mg/kg to 25 mg/kg and administration intervals ranging from 4 to 48 hours, showing a huge gap in establishing efficient doses and dosing intervals. The pharmacokinetics of analgesics vary considerably across all species that have been studied, so extrapolating data from one species to another species is not appropriate. Besides that, it has been shown that butorphanol has no significant analgesic effects in red-eared slider turtles and bearded dragons. Morphine has been proved to promote analgesia at 1.5 mg/kg, but with a consistent respiratory depression. Given this clinical perspective, tramadol, a non controlled drug, became an analgesic widely used in veterinary practice as an alternative to the use of other opioids, due to its ease of oral administration and causing significantly less respiratory depression. This study aims to employ an analytical method for plasmatic quantification of two doses of tramadol (5 e 10 mg/kg) and its metabolite o-desmethyltramadol (M1) following intramuscular and intravenous administration in red-footed tortoise. The ultimate goal is to evaluate the analgesic efficacy of tramadol through the assessment of the hind limb thermal withdrawal latencies by applying infrared thermal stimuli to the plantar surface of the tortoise. This will be a complete cross-over study with 9 red-footed tortoises (males and females). The assessment of the health status of animals will be carried out by biometry, physical examination and laboratory tests (blood count and total protein). Each animal will receive four ramdomly assigned treatments: intramuscular dosages of tramadol (5 or 10 mg/kg), intraveous dosage of tramadol (5 mg/kg) or saline solution (control), with aminimum washout period of 2 weeks between the different doses. Degree of analgesia will be assessed through measurement of hind limb thermal with drawal latencies at 0, 3, 6, 12, 24, 48, 72, and 96 hours after tramadol administration and the times will be compared to the baseline latency times to assess the degree of effectiveness of tramadol. Blood samples will be collected in the same moments of termonociceptive evaluation and used for plasma storage and phamacokinetic evaluation of tramadol and M1 with high performance liquid chromatography (HPLC). To date, very few pharmacokinetic studies have been published for analgesics in common exotic pet species and do not cover the specific nature and diversity of species. Thus, further studies are needed related to analgesia in reptiles, specifically in red-footed tortoises. (AU)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
GRIS, Vanessa Nadine. Evaluation of the antinociceptive effects and pharmacokinetics of tramadol in red-footed tortoises. 2018. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) São Paulo.

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