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

Small doses of apomorphine (0.03-0.25 mg/kg i.p.) caused a dose-dependent suppression of the ethanol-induced (2.36 g/kg, 15% v/v, i.p.) locomotor stimulation in mice and higher doses (0.5--2 mg/kg i.p.) caused a delayed suppression. The delay increased with increased doses. Very small doses of clonidine (0.025 or 0.05 mg/kg i.p.), which per se did not or only slightly affect the activity of control mice, also markedly suppressed the ethanol-induced motor stimulation. Ethanol alone (2.36 g/kg i.p.) did not significantly affect the amount of Dopa accumulating in various mouse brain regions (limbic system, corpus striatum, hemispheres and brain stem) during 30 min following administration of 3-hydroxybenzylhydrazine (NSD 1015), an inhibitor of aromatic amino-acid decarboxylase. Both the hypothermia and the locomotor stimulation by ethanol were antagonized by NSD 1015. The reduction in Dopa accumulation induced by a small dose of apomorphine (0.25 mg/kg i.p.) in the dopamine-rich regions in the mouse brain was slightly enhanced by ethanol, whereas the clonidine-induced decrease in Dopa accumulation was, if anything, reduced. In conclusion, ethanol's behavioural stimulant action in mice can be largely suppressed by apomorphine or clonidine, drugs which in the small doses used probably inhibit central catecholamine (CA) neurons.
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PMID:Antagonism of ethanol's central stimulation in mice by small doses of catecholamine-receptor agonists. 40 47

The effects of alcohol on core cooling rates (rectal and tympanic), skin temperatures, and metabolic rate were determined for 10 subjects rendered hypothermic by immersion for 45 min in 10 degrees C water. Experiments were duplicated with and without a 20-min period of exercise at the beginning of cold water immersion. Measurements were continued during rewarming in a hot bath. With blood alcohol concentrations averaging 82 mg 100 mL-1, core cooling rates and changes in skin temperatures were insignificantly different from controls, even if the exercise period was imposed. Alcohol reduced shivering metabolic rate by an overall mean of 13%, insufficient to affect cooling rate. Alcohol had no effect on metabolic rate during exercise. During rewarming by hot bath, the amount of 'afterdrop' and rate of increase in core temperature were unaffected by alcohol. It was concluded that alcohol in a moderate dosage does not influence the rate of progress into hypothermia or subsequent, efficient rewarming. This emphasizes that the high incidence of alcohol involvement in water-related fatalities is due to alcohol potentiation of accidents rather than any direct effects on cold water survival, although very high doses of alcohol leading to unconsciousness would increase rate of progress into hypothermia.
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PMID:Effect of alcohol on thermal balance of man in cold water. 49 99

Daily administration of ethanol (10-12 g/kg) to rats in a liquid diet resulted in tolerance to the hypothermic effects of ethanol. The rats also developed cross-tolerance to the hypothermic effect of morphine (15 and 30 mg/kg), whereas no cross-tolerance to the hyperthermic effect of morphine (5 mg/kg) was seen. Administration of morphine (30 mg/kg i.p.) for 3 days resulted in tolerance to morphine hypothermia and also cross-tolerance to ethanol-induced hypothermia. These studies fit with our hypothesis that tolerance and cross-tolerance among drugs develop to drug effects rather than to the drug per se. Therefore drugs sharing a common effect, even by different mechanisms, might show cross-tolerance for that effect.
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PMID:Cross-tolerance between ethanol and morphine with respect to their hypothermic effects. 51 Mar 94

The phenomenon called paradoxical undressing has been described from 33 cases of hypothermia collected from Swedish police reports. The cases were almost evenly distributed with regard to sex, age, and geographical distribution. The cases occurred more frequently in open land although cases from town areas were also found. Most incidents were recorded from November to February at low ambient temperatures, although cases were also reported at temperatures above 0 degree C. Arteriosclerosis and chronic alcoholism were important concomitant illnesses, the latter being frequent in middle-aged men. Epilepsy, diabetes, and pregnancy were present in single cases. Ethanol and other drugs were present in 67% of the males and in 78% of the females, ethanol predominating in men and various psychotropic agents in women. The mean blood ethanol concentration in males was 0.16% and in females, 0.18%. Most frequent findings at necropsy were purple spots or discoloration on the extremities, pulmonary edema, and gastric hemorrhages. It is concluded that paradoxical undressing might be explained by changes in peripheral vasoconstriction in the deeply hypothermic person. It represents the last effort of the victim and is followed almost immediately by unconsciousness and death.
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PMID:"Paradoxical undressing" in fatal hypothermia. 54 27

Selective lesions of the ascending dopamine pathways were made by bilateral injection of the neurotoxin 6-OHDA (8 micrograms/4 microliters). Catecholamine fluorescence histochemistry revealed a marked degeneration of the ascending mesostriatal and mesolimbic dopamine systems, while the hypothalamic dopamine and noradrenaline nerve terminals were unaffected. After recovery of feeding and drinking behaviors the voluntary ethanol intake was not different from that of the controls. The time of ethanol-induced narcosis and the extent of ethanol-induced hypothermia were not affected. In contrast, in a tilting-plane test conducted two months after the operation, ethanol impaired the performance of the 6-OHDA-treated rats significantly less than that of the controls. This finding suggests a role for the ascending dopamine neurons to the forebrain in the intoxicating effect of ethanol.
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PMID:On the role of ascending dopamine systems in the control of voluntary ethanol intake and ethanol intoxication. 57 55

This paper reviews some of the research on genetic bases of individual differences in ethanol tolerance of mice conducted at the Institute for Behavioral Genetics and at its predecessor laboratory at the University of California, Berkeley. Tolerance is, of course, a complex concept. Theoretical distinctions are made between tachyphylaxis and more slowly acquired tolerance and between dispositional and tissue tolerance. Pragmatically, a variety of measures (such as locomotor activity, sleep time, hypothermia) can be used to define these processes, and the different indices may yield quite different results even when they presumably indicate the same process. It is clear that an understanding of genetic influence in "ethanol tolerance" will require wide sampling of this complex domain. The work described here represents only a beginning, but it may illustrate the general approaches that are available for addressing the issue.
Drug Alcohol Depend
PMID:Genetics and ethanol tolerance. 57 46

In experiments with white rats, chlorpromazine, diazepam and imirpramine injected intraperitoneally in the dose of 20 mg/kg and imipramine and diazepam in the dose of 50 mg/kg did not enhance the acute toxicity of ethanol expressed as LD50. Only chlorpromazine in the dose of 50 mg/kg i.p. increased toxicity of ethanol. However, the aforementioned drugs intensified the central action of ethanol by prolonging (except imipramine) duration of narcotic sleep and motor incoordination, and potential ethanol-induced hypothermia.
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PMID:The influence of chlorpromazine, diazepam and imipramine on the central action of ethanol. 61 4

On the basis of the above discussion, a number of useful guidelines appear for the anesthetic management of alcohol and drug abusers. 1. Because of the decreased ability of intoxicated patients to withstand hemorrhage, blood replacement therapy should probably be instituted earlier than in the nonintoxicated patient. 2. Because the chronic alcoholic may actually be iso-osmotically overhydrated, fluid therapy must be planned with care. 3. Because of the tendency to hypoglycemia, glucose should be added to the fluid management regimen. 4. Because of the enzyme induction effect of chronic ETOH ingestion, anesthetic agents that are in part metabolized (methoxyflurane, halothane, fluroxene) are perhaps best avoided. Increased ability to metabolize anesthetic agents appears to be associated with toxicity. 5. Because ETOH is a CNS depressant and has been shown to have amnesia-inducing properties, supplementation of nitrous oxide-relaxant technique with narcotics or other depressant drugs should be reduced, if not eliminated. 6. Because acutely intoxicated individuals are more prone to hypothermia, their core temperature should be monitored intraoperatively. All intravenous fluids should be warmed and a warming blanket should be employed, if necessary, to maintain body temperature. 7. Because of the sympathomimetic effect of many of the drugs, pulse and blood pressure can be misleading in the assessment of blood loss.
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PMID:Preanesthetic care. Intoxication and trauma. 96 73

Mice undergoing withdrawal after chronic ethanol consumption were found to be hypothermic if kept at room temperature. The extent of the hypothermia correlated well with the behavioral withdrawal symptoms and could be used as a quantitative measure of the severity and time course of the withdrawal syndrome. Placing mice in a cold environment (4 degrees C) exacerbated the hypothermia whereas placing animals at 34 degrees C reversed the hypothermia and produced hyperthermia. It was concluded that the temperature set point mechanism and the ability to regulate around this set point was disturbed in animals physically dependent on alcohol. During consumption of the ethanol-containing diets, mice exhibited tolerance to the hypothermic effects of an acutely administered dose od ethanol. Tolerance to the hypothermic effects of ethanol mirrored the development of behavioral tolerance as measured by performance on a tilting plane. Temperature and behavioral tolerance were both shown to extend well beyond the period of the withdrawal syndrome. Ethanol-treated mice were found to be cross-tolerant to the hypothermic effects of barbiturates but not to the hypothermia produced by the monoamine oxidase inhibitor, pargyline.
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PMID:Body temperature in mice: a quantitative measure of alcohol tolerance and physical dependence. 98 76

Neurophysiological, neurochemical and behavioral studies of the effects of ethanol on the nervous system have so far failed to identify specific, direct, primary mechnisms of action that may account for the typical pattern of alcohol intoxication in vivo. Electroencephalogram and evoked response studies indicate biphasic effects in the intact subject, which may correlate better with the level of arousal than with a specific drug action. Effects on spinal reflexes are also biphasic, probably representing the net result of direct influence on resting membrane potential, primary afferent depolarization, and neurotransmitter release. With the exception of its inhibitory effect on release of oxytocin, vasopressin and possibly other hypothalamic peptides, ethanol does not appear notably different in its spectrum of effects from a wide range of other hypnotics, anesthetics and minor tranquilizers. Interpretation of the findings is complicated by the fact that functional alteration of any given neuronal system by ethanol in vivo may reflect a) direct local action of ethanol on the cells under study, b) change in the input to those cells because of an action elsewhere in the nervous system, c) effects of ethanol metabolites, or d) indirect consequences of decreased blood flow, oxygen or metabolite supply, hormonal action, or hypothermia, due to disturbances of homeostasis in the whole body as a result of deep intoxication. To date, attempts to circmvent b, c and d by the study of brain tissue in vitro have shown consistent effects of ethanol only at concentrations well above those that are meaningful in vivo. Relatively specific patterns of action of different drugs in vivo may prove to be largely dependent on their customary rates and routes of administration, and on summation of minor differences in the dose-response curves with different types of neuron, even though the basic types of molecular action may be essentially similar.
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PMID:Direct effects of ethanol on the nervous system. 109 39


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