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)

1. The aim of this investigation was to determine whether supersensitivity of isolated atria to sympathomimetic amines following pretreatment with reserpine was evident at low temperatures, which alone induced supersensitivity. 2. Cumulative dose-response curves for the positive inotropic and chronotropic responses of isolated guinea-pig atria to isoprenaline and the partial agonist salbutamol were plotted as a percentage of the maximum response to isoprenaline. 3. In atria from reserpine-pretreated guinea-pigs set up at 38 degrees C, supersensitivity of both rate and tension responses was observed as a shift of the curves to the left and an increase of the maximum responses to salbutamol. Tension responses were potentiated more than rate responses. At 30 degrees C the supersensitivity became less apparent and at 25 degrees C was virtually absent. 4. The dose-response curves in untreated atria at low temperatures revealed that hypothermia itself produced supersensitivity of rate and tension responses. The dose-response curves were displaced to the left and the salbutamol maxima were raised so that at 25 degrees C it became almost a full agonist. The hypothermia-induced supersensitivity was therefore sufficient to mask any supersensitivity resulting from pretreatment with reserpine. 5. The hypothermia-induced supersensitivity of the rate response was dependent upon the method of plotting. When plotted in absolute units of beats per min no supersensitivity of the rate response was evident. Supersensitivity of the tension response at the lower temperatures and of both rate and tension responses following pretreatment with reserpine were independent of the plotting method.
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PMID:The influence of temperature upon reserpine-induced supersensitivity of guinea-pig isolated atria to isoprenaline and salbutamol. 85 68

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

The pharmacological properties of two selective inhibitors of monoamine oxidase (MAO) type B, L-deprenyl and MDL 72145 [(E)-2-(3,4-dimethoxyphenyl)-3-fluoroallylamine, HCl], have been investigated in rats and mice in relation to their effects on MAO. Selective inhibition of MAO B achieved following 18 h pretreatment with L-deprenyl and/or MDL 72145 did not per se lead to prominent pharmacological activity; no effects were seen in the mouse "Behavioural Despair" test, hypothermia induced by reserpine in mice was neither prevented nor reversed and there was no change in the cardiovascular responsiveness of the pithed rat to tyramine, noradrenaline or stimulation of the spinal sympathetic outflow. L-Deprenyl differed from MDL 72145 in that short term treatment with this drug caused positive effects in the "Behavioural Despair" test, reversal of reserpine hypothermia, indirect sympathomimetic stimulation of blood pressure and heart rate in the pithed rat and ipsilateral rotation in rats with unilateral nigro-striatal lesions. Qualitatively similar effects were seen with dexamphetamine. The marked difference between the pharmacological effects of MDL 72145 and L-deprenyl despite equivalent inhibition of MAO B suggests that many of the pharmacological actions of L-deprenyl result from its amphetamine-like sympathomimetic properties. MDL 72145 can, therefore, be considered a more reliable tool with which to explore the functional importance of MAO B inhibition in experimental animals and man.
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PMID:The functional consequences of inhibition of monoamine oxidase type B: comparison of the pharmacological properties of L-deprenyl and MDL 72145. 393 59

Positive inotropic and chronotropic responses of guinea-pig isolated left and right atria to sympathomimetic amines were examined at bath temperatures of 38, 30 or 25 degrees C. The concentration-response curves to isoproterenol and orciprenaline were displaced to the left by cooling, indicating hypothermia-induced supersensitivity. The affinities of isoproterenol and orciprenaline were determined as their dissociation constants (pKA) from antagonism of their responses by either the functional antagonist carbachol or Ro 03-7894 which is reported to be an irreversible beta-adrenoceptor antagonist. By both methods of calculation, the affinities of isoproterenol and orciprenaline for the beta-adrenoceptors mediating inotropic and chronotropic responses were increased by lowering the temperature. In contrast, the affinity of practolol, measured as the pA2 for competitive antagonism of the isoproterenol- and orciprenaline-induced inotropic and chronotropic responses, did not increase with cooling. Thus hypothermia-induced supersensitivity is associated with an increase in agonist affinity only, which indicates a fundamental temperature-dependent difference between agonist and antagonist interactions with the beta-adrenoceptor.
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PMID:A fundamental temperature-dependent difference between beta-adrenoceptor agonists and antagonists. 609 Aug 30

1 Positive inotropic and chronotropic responses to guinea-pig isolated left and right atria respectively to the sympathomimetic amine orciprenaline were recorded. 2 Pretreatment of animals with reserpine for 3 days produced supersensitivity of both the inotropic and chronotropic responses. Lowering the bath temperature from 38 degrees to 30 degrees C produced supersensitivity of untreated atria to the inotropic responses only. 3 Irreversible beta-adrenoreceptor antagonism of orciprenaline by Ro 03-7894 was demonstrated by a persistent depression of the maximum inotropic and chronotropic responses after a prolonged washout from the bath (3 h). 4 The depression of the maximum rate and tension responses by Ro 03-7894 was less in atria from reserpine-pretreated animals. 5 The maxima were also depressed less at the lower bath temperature of 30 degrees C. However, when atria were cooled during the incubation with Ro 30-7894, the maxima were still depressed to the 38 degrees C level. 6 That these results suggest either a receptor proliferation or change in efficacy as possible mechanisms for reserpine- and hypothermia-induced supersensitivity is discussed.
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PMID:The use of an irreversible beta-adrenoreceptor antagonist to examine reserpine- and hypothermia-induced supersensitivity of guinea-pig atria. 612 88

Many beta-adrenoceptor-blocking agents are well studied today. They differ from one another not only in their pharmacologic profiles (cardioselectivity, intrinsic sympathomimetic activity, membrane-stabilizing activity) but also in their metabolic and pharmacokinetic profiles. The profiles of the following 10 beta blockers have been compared: acebutolol, atenolol, labetalol, metoprolol, nadolol, oxprenolol, pindolol, propranolol, sotalol, and timolol. Differences in the aromatic ring structure lead to differences in lipophilic characteristics. They in turn influence the pharmacokinetic parameters such as hepatic extraction ratio, protein binding, volume of distribution, and the ratio of renal versus hepatic clearance. Incomplete oral bioavailabilities are reported both for the lipophilic drugs (e.g., labetalol, oxprenolol, and propranolol) due to extensive first-pass metabolism and for the more hydrophilic drugs (e.g., atenolol, acebutalol, and nadolol) due to medium or low absorption. Low bioavailabilities (as in the case of propranolol) are the source of large biologic variations, nonlinearities, or increased plasma levels with food, with age, in nonsmokers, or in disease states (e.g., hypothermia and renal, hepatic, celiac, Crohn's, or inflammatory disease). The pharmacokinetic comparison in this series of beta blockers reveals that pindolol with its medium lipophilicity has some important advantages. A low daily dosage is possible because of the high bioavailability, the low first-pass effect, the moderate metabolism, and the potency of this drug. Due to the low first-pass effect and the low daily dosage there are no saturation effects, and a good dose linearity is observed. This, combined with moderate metabolism and low protein binding, results in small variability and a good predictability in plasma levels and drug effects. Due to the balanced renal and hepatic clearance, no relevant drug accumulation has to be expected in patients with liver or kidney impairment.
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PMID:Pharmacokinetic comparison of pindolol with other beta-adrenoceptor-blocking agents. 612 95

The positive inotropic responses of guinea-pig left atria and papillary muscles and positive chronotropic responses of right atria to sympathomimetic amines were examined at 38 degrees and 30 degrees C. At the lower temperature, supersensitivity to orciprenaline and isoprenaline was exhibited as shifts of the dose-response curves to the left and significant reductions in EC50 values. This supersensitivity could not be attributed to reduced metabolism since the experiments were performed in the presence of metanephrine (10(-5)M) and U-0521 (3',4'-dihydroxy-2-methylpropiophenone) (10(-4)M) as inhibitors of extraneuronal uptake and catechol-O-methyltransferase (COMT) respectively, and the agonists are not susceptible to neuronal uptake. After incubation of the tissues with Ro 03-7894 (1-(5-chloracetylaminobenzfuran-2-yl)-2-isopropylaminoethanol), followed by its prolonged washout (greater than 2h), the maximum responses to isoprenaline and orciprenaline were depressed, confirming the apparently irreversible beta-adrenoceptor antagonism. Dissociation constants (KA) for isoprenaline and orciprenaline were determined from the equiactive concentrations obtained before (A) and after (A') incubation with Ro 03-7894, plotted as 1/A against 1/A' (KA = (slope-1)/intercept). KA values were the same for orciprenaline in the three cardiac preparations and for isoprenaline in the atria. This applied at 38 degrees and 30 degrees C and indicates that the beta-adrenoceptors mediating the inotropic and chronotropic responses of the guinea-pig heart do not differ. The KA values of both agonists were, however, consistently and significantly lower at 30 degrees than at 38 degrees C, indicating an increase in affinity. 8 It is concluded that hypothermia-induced supersensitivity of cardiac tissue to sympathomimetic amines is associated with an increase in their affinity for the B-adrenoceptors.
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PMID:Temperature-induced changes in dissociation constants (KA) of agonists at cardiac beta-adrenoceptors determined by use of the irreversible antagonist Ro 03-7894. 614 43

4-Amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), in this study briefly called amezinium, was tested for possible central effects taking particular account of the mechanisms of action found for this substance in other studies. 1. The most conspicuous action of amezinium was in modifying reserpine-induced ptosis and reserpine-induced hypothermia. When amezinium is given before reserpine, the ED50 values are 0.15 and 3.9 mg/kg p.o. for both mouse and rat. These effects can be explained by a peripheral site of action since peripheral sympathomimetic effects can also be demonstrated in this dose range. Higher doses (10 mg/kg and upwards p.o.) were required to abolish reserpine-induced hypothermia 17 h after reserpine administration, an effect which probably requires a central site of action. But for imipramine, desipramine and pargyline the effective doses are the same in both experimental models (administration before and after reserpine, respectively). 2. Amezinium potentiated the effect of a threshold dose of L-dopa. Based on the central symptoms, higher doses (10 mg/kg p.o.) were also required for this effect. 3. With blood pressure increasing doses, the sleeping-waking pattern was modified in that duration and number of REM-episodes were reduced; in cats there was no parallel increase of wakefulness whilst in rats there was a slight relative increase of wakefulness. 4. Amezinium, particularly at high doses (46.4 mg/kg and upwards), exhibited a central depressant effect on the spontaneous behaviour of mice and rats and on orientational hyperactivity of mice. Based on the modification of aggregation toxicity, the effect of methamphetamine was reduced. In no dose range was there any evidence of methamphetamine-like effects (increase of motor activity, inhibition of food intake and increase of aggregation toxicity). 5. Amezinium did not affect the duration of hexobarbital anaesthesia or the coordination of mice on a rotating rod. 6. The acute toxicity of amezinium in mice and rats was low. The oral LD50 for mice was 1630 mg/kg and for rats 1410 mg/kg.
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PMID:Pharmacology of amezinium, a novel antihypotensive drug. VI. Effect on central nervous functions. 719 73

The effects of intracerebroventricular (i.c.v.) injections of sympathomimetic drugs on thermoregulatory functions in conscious rats maintained at low (8 decrees C), moderate (22 degrees C), and high (30 degrees C) ambient temperatures were assessed. Norepinephrine, tyramine, and ephedrine each produced hypothermia at ambient temperature (Ta) 8 degrees C and hyperthermia at Ta 22 and 30 degrees C. At Ta 8 degrees, the hypothermia in response to norepinephrine, tyramine, and ephedrine was due to decreased metabolic rate (M) whereas at Ta 22 degrees C the hyperthermia was due to cutaneous vasoconstriction. AT Ta 22 degrees C, the hyperthermia in response to norepinephrine and tyramine was due to cutaneous vasoconstriction whereas the hyperthermia in response to ephedrine was brought about by increased M (due to behavioral excitation). Intracerebroventricular injection of epinephrine produced hypothermia followed by hyperthermia at Ta 8 and 22 degrees C. The hypothermia was due to decreased M whereas the hyperthermia was due to cutaneous vasoconstriction and increased M. AT Ta 30 degrees C, epinephrine led to a reduction in cutaneous temperature and hyperthermia. Furthermore, i.c.v. administration of phenylephrine produced a decreased M and hypothermia Ta 8 degrees C and an increased M (due to behavioral excitation) and hyperthermia at Ta 30 degrees C. At Ta 22 degrees C, phenylephrine produced hyperthermia (due to cutaneous vasoconstriction and increased M) preceded by hypothermia (due to decreased M). Moreover, the temperature effects induced by norepinephrine were antagonized by pretreatment with the adrenoceptor antagonist phentolamine. In general, the data indicate that activation of central adrenoceptors with sympathomimetic drugs inhibits both heat production and heat loss mechanisms in the rat.
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PMID:Intracerebroventricular injection of sympathomimetic drugs inhibits both heat production and heat loss mechanisms in the rat. 722 27

Naphazoline, a sympathomimetic and an imidazoline derivative, is used as 0.05-0.1% solution for local decongestion of the nasal and ocular mucosa. In excessive dosage, or if ingested by accident, may cause depression of the central nervous system (disturbances of consciousness progressing to coma), hypothermia, bradycardia and sweating. These naphazoline effects are particularly strongly pronounced in children. Anglo-Saxon pharmacotherapy excludes the application of naphazoline nasal drops in children younger than six years, whereas the Croatian pharmacotherapeutic literature (and practice) allows its use even in infancy. At the Kantrida Paediatric Clinic, Clinical Hospital Centre in Rijeka, 11 children with signs of intoxication with naphazoline nasal drops were hospitalized from 1990 to 1992. The symptoms pertaining to the central nervous system i.e. disturbances of consciousness in the form of somnolence were clearly marked in all children. Some children developed skin pallor, bradycardia, bradypnoea and hypothermia. Resolution occurred within 24 hours and the findings returned to normal values. Clinical picture followed by rapid resolution and normal findings, with a personal history of drug taking, is a safe indication for diagnosis. There are several reasons to account for intoxication (drops difficult to use with children, containers inadequate for proper dosage), but the major factor is the age of the patient--all hospitalized children were younger than six years. It is pointed out that administration of naphazoline drops at an early age is not advisable.
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PMID:Naphazoline nasal drops intoxication in children. 806 10


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