title: A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice.
abstract: Medetomidine is a relatively new sedative analgesic drug that is approved for use in dogs in Canada. It is the most potent alpha2-adrenoreceptor available for clinical use in veterinary medicine and stimulates receptors centrally to produce dose-dependent sedation and analgesia. Significant dose sparing properties occur when medetomidine is combined with other anesthetic agents correlating with the high affinity of this drug to the alpha2-adrenoreceptor. Hypoventilation occurs with medetomidine sedation in dogs; however, respiratory depression becomes most significant when given in combination with other sedative or injectable agents. The typical negative cardiovascular effects produced with other alpha2-agonists (bradycardia, bradyarrhythmias, a reduction in cardiac output, hypertension +/- hypotension) are also produced with medetomidine, warranting precautions when it is used and necessitating appropriate patient selection (young, middle-aged healthy animals). While hypotension may occur, sedative doses of medetomidine typically raise the blood pressure, due to the effect on peripheral alpha2-adrenoreceptors. Anticholinergic premedication has been recommended with alpha2-agonists to prevent bradyarrhythmias and, potentially, the reduction in cardiac output produced by these agents; however, current research does not demonstrate a clear improvement in cardiovascular function. Negatively, the anticholinergic induced increase in heart rate potentiates the alpha2-agonist mediated hypertension and may increase myocardial oxygen tension, demand, and workload. Overall, reversal with the specific antagonist atipamezole is recommended when significant cardiorespiratory complications occur. Other physiological effects of medetomidine sedation include; vomiting, increased urine volumes, changes to endocrine function and uterine activity, decreased intestinal motility, decreased intraocular pressure and potentially hypothermia, muscle twitching, and cyanosis. Decreased doses of medetomidine, compared with the recommended label dose, should be considered in combination with other sedatives to enhance sedation and analgesia and lower the duration and potential severity of the negative cardiovascular side effects. The literature was searched in Pubmed, Medline, Agricola, CAB direct, and Biological Sciences.
authors.affiliation: Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1. msinclai@ovc.uoguelph.ca
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Sinclair
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000009:adverse effects / Q000494:pharmacology*; D019162:Anesthetics, Combined / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D004285:Dogs / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000494:pharmacology; D020926:Medetomidine / Q000009:adverse effects / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012137:Respiratory System / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D019162:Anesthetics, Combined; D006993:Hypnotics and Sedatives; D011942:Receptors, Adrenergic, alpha; D020926:Medetomidine