Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sedative effects of medetomidine, a potent selective and specific alpha 2-adrenoceptor agonist, were evaluated in pigs using 5 different doses (30, 50, 80, 100 and 150 micrograms/kg of body weight) and compared with those of xylazine (2 mg/kg). Atropine (25 micrograms/kg) was mixed with both drugs to prevent severe bradycardia. All drugs were administered intramuscularly. Medetomidine at a dosage of 30 micrograms/kg produced more potent sedation than xylazine. The depth of sedation induced by medetomidine was dose dependent within the range from 30 to 80 micrograms/kg. At 100 or 150 micrograms/kg, the depth of sedation was mostly the similar level to that at 80 micrograms/kg but the duration was prolonged. The degree of muscle relaxation produced by medetomidine also seemed to be dose dependent from 30 to 80 micrograms/kg and was stronger than that produced by xylazine. An increase in the duration of muscle relaxation was dose dependent up to 150 micrograms/kg. No analgesic effect was produced by xylazine, however moderate analgesia was obtained by medetomidine. There were no marked changes in heart rate and respiratory rate during the observation period in pigs of any groups, however mild hypothermia after the administration of both drugs was observed. From these results, medetomidine has a significant and dose-dependent sedative effects which are much more potent than that of xylazine, and a combination of 80 micrograms/kg of medetomidine and 25 micrograms/kg of atropine is suitable for sedation with lateral recumbency and moderate muscle relaxation without notable side effects in pigs.
 ...
PMID:Sedative effects of medetomidine in pigs. 139 Nov 73

Medetomidine (MED) is a veterinary sedative whose mode of action is activation of alpha-2 adrenoceptors. Because the carbon atom which separates the two ring systems is methylated, there is a center of stereochemical asymmetry in the molecule. The resulting enantiomers, d-MED and l-MED have recently become available for study. The biological activity of MED, as is now demonstrated in rats in vivo, seems to reside almost exclusively in the d-MED form. Only at extremely high doses (e.g., 10 mg/kg) does l-MED exert any effects, interpreted as alpha-2 adrenoceptor antagonism. In contrast, doses of d-MED as low as 30 micrograms/kg cause sedation, hypothermia and induce neurochemical changes in norepinephrine and 5-hydroxytryptamine metabolism in brain characteristic of alpha-2-agonists (decreases in concentrations of biogenic amine metabolites, turnover and increases in concentration of parent amine). The most sensitive neurochemical indicator of the alpha-2-agonist action of d-MED was the concentration of unconjugated 3-methoxy-4-hydroxy-phenyethylene glycol in rat cerebral spinal fluid, doses of d-MED as low as 10 micrograms/kg caused a significant reduction in this norepinephrine metabolite. Simultaneous administration of the specific alpha-2 adrenoceptor antagonist, atipamezole (1 mg/kg), effectively inhibited the behavioral and most of the neurochemical actions of d-MED (100 micrograms/kg). It is concluded that the enantiomers of MED may be extremely useful in elucidating structure action relationships at alpha-2 adrenoceptors.
 ...
PMID:Comparison of the behavioral and neurochemical effects of the two optical enantiomers of medetomidine, a selective alpha-2-adrenoceptor agonist. 168 87

The effects of medetomidine [20 and 40 micrograms/kg of body weight (BWT) i.m.] followed by sodium pentobarbital were assessed and compared with the effects of xylazine (1 mg/kg of BWT i.m.) in three groups each of 6 dogs. The effects of atipamezole as a specific antidote after anaesthesia were also studied. Medetomidine produced a reliable sedation which was clinically comparable with the xylazine premedication. 40 micrograms/kg medetomidine induced lower induction (non-significantly), total (p less than 0.05), anaesthetic (non-significantly) and anaesthetic per hour (non-significantly) doses of Na pentobarbital compared to the 20 micrograms/kg medetomidine and the xylazine protocols. No significant differences in the total number of re-injections were found between the sedative protocols although a gradual increase in number of re-injections per hour was observed. Significant decreases in heart and respiration rates were noticed during anaesthesia in all groups (p less than 0.01). The heart and respiration rates during anaesthesia in the 40 micrograms/kg medetomidine group were always significantly lower compared to the xylazine group. Body temperature decreased gradually in time during anaesthesia in all groups (p less than 0.05 after 1 hour, p less than 0.01 after 2 and 3 hours) without significant differences between the groups. The extubation time in the medetomidine protocols without antagonisation was significantly greater (p less than 0.01) than the extubation time after antagonisation with atipamezole.
 ...
PMID:Comparative trial of xylazine and medetomidine as preanaesthetics prior to Na pentobarbital anaesthesia in dogs. 212 94

Medetomidine, (+/-)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole, is a very potent, selective and specific full agonist at both pre- and postsynaptic alpha 2-adrenoceptors as demonstrated in several models both in vitro and in vivo. In receptor binding experiments the alpha 2/alpha 1 selectivity ratio of medetomidine is 1620 compared to 260, 220 and 160 for detomidine, clonidine and xylazine, respectively. The alpha 2-adrenoceptor activity of medetomidine resides predominantly in its d-enantiomer (dexmedetomidine). Medetomidine induces a dose-dependent decrease in the release and turnover of noradrenaline, dopamine and serotonin in the CNS as measured by changes in metabolite concentrations or using pharmacological intervention techniques. Inhibition of sympathetic tone in the CNS by medetomidine leads for a characteristic pattern of pharmacodynamic responses including e.g. hypotension, bradycardia, sedation, relief of anxiety, analgesia and hypothermia. The potent, dose-dependent sedative effects of medetomidine have been demonstrated in several classical animal models (e.g. decrease in spontaneous motility in rats and mice, potentiation of barbiturate-induced anaesthesia in rats and mice, induction of sleep in young chicks). At high doses medetomidine has hypnotic of anaesthetic effects, a property which distinguishes it clearly from detomidine, clonidine and other alpha 2-agonists. The pharmacological, neurochemical and behavioral effects of medetomidine can be inhibited by prior, simultaneous of subsequent administration of a selective and specific alpha 2-antagonist, atipamezole. Besides verifying that the main pharmacodynamic effects of medetomidine are alpha 2-mediated, this finding forms a strong basis for the use of atipamezole as a reversing agent against medetomidine-induced effects in veterinary practice.
 ...
PMID:Pharmacological profiles of medetomidine and its antagonist, atipamezole. 257 Dec 75

Medetomidine is a sedative and analgesic drug intended for use in dogs and cats but it can also be successfully used in many other species. The effect of medetomidine is dose dependent at the recommended dose range (10-80 micrograms/kg for dogs and 50-150 micrograms/kg for cats). At doses higher than the recommended ones the strength of sedation does not increase, only the duration of the effect. From the cardiovascular changes induced with medetomidine, the profound bradycardia is most prominent. It can be transiently prevented with atropine or glycopyrrolate medication. An initial increase in arterial blood pressure followed by a longer lasting slightly hypotensive or normotensive period can be observed. Respiratory frequency tends to decrease but the changes stay within normal limits for resting animals. Vomiting may occur during the induction period of sedation. Occasional muscle jerks can be observed. Hypothermia has been reported in every animal sedated with medetomidine. Medetomidine can be used as preanaesthetic prior to ketamine, barbiturate and halothane anaesthesia.
 ...
PMID:Introduction to the clinical pharmacology of medetomidine. 257 Dec 83

1. Administration of the irreversible antagonist, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, (EEDQ, 2 mg kg-1, i.p.) to mice reduced binding of [3H]-RX 821002 (2-methoxy-idazoxan) to alpha 2-adrenoceptors in whole mouse brain by 75% 24 h later. The receptor binding returned over time only being reduced by 25% by 16 days post administration; the time taken for binding to return to 50% of control levels was estimated to be 5.25 days. 2. EEDQ administration also resulted in the loss of the sedative effect of the alpha 2-adrenoceptor agonist, medetomidine, measured by the holeboard test of directed exploration and locomotor activity. Agonist-induced sedation returned to control values by 8 days post EEDQ administration. 3. EEDQ administration also resulted in the loss of the hypothermic response to medetomidine (0.1 mg kg-1, i.p.). Medetomidine-induced hypothermia returned to control values by 12 days post EEDQ administration. 4. Pretreatment with the selective alpha 2-adrenoceptor antagonist, RX 821002 (0.1-3.0 mg kg-1, i.p.) 45 min before EEDQ prevented the loss of alpha 2-adrenoceptors as well as the blockade of medetomide-induced sedation and hypothermia by EEDQ. 5. The results of these experiments indicate that there is significant receptor reserve for alpha 2-adrenoceptor-mediated behavioural and physiological responses.
 ...
PMID:Covariation of alpha 2-adrenoceptor density and function following irreversible antagonism with EEDQ. 792 12

Seventy-two healthy dogs required sedation and analgesia for a variety of procedures causing discomfort or pain. They were treated either with the alpha 2-agonist medetomidine at 40 micrograms/kg (15 intravenously and 17 intramuscularly), or 80 micrograms/kg (15 intravenously and 15 intramuscularly) or with xylazine plus l-methadone (1.0 mg)(10 intravenously). The levels of sedation, analgesia and safety were compared clinically and by measurements of the effects on the electrocardiogram (ECG) and blood gases, body temperature, haematology and clinical chemistry. Sedation was achieved reliably with both medetomidine and xylazine plus l-methadone but its onset, depth and duration were influenced by the dose and route of administration. In the medetomidine-treated dogs, intravenous administration resulted in more rapid sedation and the effects of the higher dose were deeper and longer lasting. The small dogs receiving 40 micrograms/kg may have been underdosed. The initial analgesic effects in response to a pin prick to the body surface were sufficient and similar for both drugs, except for the intramuscular dose of 40 micrograms/kg medetomidine. Analgesia for the clinical procedures was less reliable with medetomidine and was not always adequate even at the high dose, but xylazine plus l-methadone assured analgesia in almost every case. Medetomidine resulted in marked bradycardia, lasting as long as the sedation and the ECG revealed a sinus arrhythmia with sinoatrial and atrioventricular blocks grade I and II as a sign of interference with transduction. The bradycardia with xylazine plus l-methadone was less pronounced. A decrease in respiratory rate accompanying sedation had no influence on blood gases and blood acidity in the dogs treated with medetomidine but caused a respiratory acidosis with xylazine plus l-methadone. Body temperature decreased with all treatments for the duration of the period of sedation. Blood glucose concentration increased to a similar extent in all treatment groups, but all other haematological and clinicochemical variables remained unchanged. Treatment with the specific alpha 2 antagonist, atipamezole, reversed the sedation and cardiovascular and pulmonary effects due to medetomidine within minutes.
 ...
PMID:Clinical comparison of medetomidine with xylazine/l-methadone in dogs. 865 Sep 15

Medetomidine is a relatively new sedative analgesic in dogs and cats but some precautions are required when using it. It is a potent alpha 2-adrenoceptor agonist and stimulates receptors centrally to produce dose-dependent sedation and analgesia and receptors centrally and peripherally to cause marked bradycardia and decrease the cardiac output. While hypotension occurs frequently, higher doses of the sedative can raise the blood pressure due to an affect on peripheral receptors. Slowing of the respiratory rate is a frequent effect of medetomidine with some dogs showing signs of cyanosis. Other actions that follow medetomidine use are slowing of gastrointestinal motility, hypothermia, changes to endocrine function and, occasionally, vomiting and muscle twitching. The clinical use of medetomidine in dogs and cats is discussed. Recommended dose rates are presented along with precautions that should be taken when it is used alone for sedation, as an anaesthetic premedicant or in combination with ketamine, propofol or opioids. Hypoxaemia occurs frequently in dogs given medetomidine and propofol. The actions of medetomidine can be rapidly reversed with the specific alpha 2-adrenoceptor antagonist, atipamezole, which is an advantage because undesirable and sedative actions of medetomidine can be terminated.
 ...
PMID:Medetomidine sedation in dogs and cats: a review of its pharmacology, antagonism and dose. 888 60

Medetomidine was injected by the intramuscular route at the rates of 3 and 5 microg/kg body weight into two groups of Indian elephants (Elephas maximus). Sedation was induced at 6.20 (0.81) and 5.90 (0.60) min respectively after injection. The duration of anaesthesia was 66.20 (10.4) and 134.20 (24.12) min, respectively and recovery occurred at 125.80 (25.23) and 205.89 (29.3) min. The notable signs of sedation exhibited by the elephants were protrusion of penis, complete relaxation of trunk, flaccidity of tail and drooping of the ears with a head down position. During sedation, physiological parameters recorded were bradycardia, decreased respiration and hypothermia.
 ...
PMID:Medetomidine a novel immobilizing agent for the elephant (Elephas maximus). 1244 92

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.
 ...
PMID:A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice. 1466 51


1 2 Next >>