Medical problems of surgical patients. Hypertension and ischaemic heart disease.
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Pre-existing disease in the form of hypertension or ischaemic heart disease may increase morbidity and mortality in patients presenting for anaesthesia and surgery. The interaction of these two cardiovascular conditions in relation to anaesthesia has been studied in a series of 115 patients. The results did not support the view that antihypertensive drugs and beta-receptor blocking agents should be withdrawn before anaesthesia and surgery. The main cause for concern in providing anaesthesia for these patients is that sympathetic nervous activation induced either by anaesthetic manoeuvres or by surgical stimulation may lead to reflex cardiovascular responses which, by increasing myocardial oxygen demand, lead to episodes of myocardial ischaemia. In this respect beta-receptor blocking drugs appear to have a protective effect on the ischaemic myocardium. (+info)
Investigation of diazepam lipospheres based on Witepsol and lecithin intended for oral or rectal delivery.
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Diazepam was incorporated in lipospheres prepared by high pressure homogenization of melted Witepsol (10%) dispersed in aqueous lecithin (2.4%). Diazepam content was 0.4% and more than 98% of the dose was found to be encapsulated in the lipospheres. Although the initial mean particle size was 0.3 micron, the liposhperes agglomerated during storage and this phenomenon was not eliminated by increasing lecithin concentration to 4% or incorporation of oleic acid (0.1%) and co-surfactants, polysorbate 80 (0.5%) or poloxamer (up to 6%). The formulation was not able to mask effectively bitter taste of diazepam, even when lipids of higher melting temperature, namely glyceryl tripalmitate or stearic acid, were introduced. (+info)
Anaesthesia for injection of bleeding oesophageal varices.
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Patients with haemorrhage from oesophageal varices associated with portal hypertension are poor risks for anaesthesia and surgery. One method of controlling such haemorrhage is injection of the oesophageal varices (sclero-therapy) via an oesophagoscope. Careful preoperative preparation and use of the Sengstaken-Blakemore tube in combination with the anaesthetic technique of intermittent Althesin and suxamethonium with artificial ventilation with nitrous oxide and oxygen enables sclerotherapy to be carried out successfully. (+info)
Diazepam-binding inhibitor/acyl-CoA-binding protein mRNA and peripheral benzodiazepine receptor mRNA in endocrine and immune tissues after prenatal diazepam exposure of male and female rats.
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Peripheral benzodiazepine (BDZ) receptor (PBR) and diazepam-binding inhibitor/acyl-CoA-binding protein (DBI/ACBP) characterized as a ligand at central BDZ receptors, at PBR with involvement in the regulation of steroidogenesis, and as an intracellular acyl-CoA transporter, are both known to interact with BDZ in adult systems. We investigated their expression after prenatal exposure to BDZ. Diazepam (1.25 mg/kg per day s.c.) was administered to time-pregnant Long Evans rats from gestational day (GD) 14 to 20. Expression of mRNAs encoding for PBR and for DBI/ACBP was studied in the same animals with (33)P-labeled 60 mer oligonucleotides (oligos) by in situ hybridization at GD20, and with (32)P-labeled oligos by Northern blot in steroidogenic and immune organs at postnatal day (PN) 14 and in adult offspring. Prenatal diazepam increased DBI/ACBP mRNA expression in male fetal adrenal and in fetal and PN14 testis. Thymus exhibited increased DBI/ACBP mRNA in male fetuses and in adult female offspring, and reduced organ weight at PN14 in both sexes. In female spleen, an increase in DBI/ACBP mRNA and a decrease in PBR mRNA was seen at PN14. Apart from the finding in spleen, no drug-induced changes in PBR mRNA were observed. The effects of prenatal diazepam were superimposed on treatment-independent sex differences in DBI/ACBP mRNA and PBR mRNA expression. Our data indicate that expression of DBI/ACBP mRNA in steroidogenic and immune organs can be affected by exposure to BDZ during ontogeny, while PBR mRNA expression appears to be less sensitive. They further reveal marked sex differences in the developmental patterns of the two proteins during pre- and postpubertal ontogeny. (+info)
Role of ketamine in convulsions.
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It can be concluded from the present study that ketamine showed dose-dependent anticonvulsant effect on MES in mice. It is presumed that this anticonvulsant effect of ketamine could be due to blockade of excitatory amino acid NMDA receptors. It was potentiated by anticonvulsants like diazepam and DPH but was found to be insensitive to naloxone. These findings suggest the involvement of NMDA receptors and their antagonists in epilepsy. Ketamine thus can be given as add-on therapy in refractory cases, and may prove to be useful as an anticonvulsant in future. (+info)
Flibanserin has anxiolytic effects without locomotor side effects in the infant rat ultrasonic vocalization model of anxiety.
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This study compared the effects of flibanserin, a novel 5-HT(1A) agonist/5-HT(2A) antagonist; diazepam, a traditional anxiolytic; and imipramine, a traditional antidepressant, on separation-induced ultrasonic vocalizations (USVs), locomotor behaviour, negative geotaxis and body temperature of 7 - 8-day-old rat pups. Flibanserin (5, 10, 25 and 50 mg kg(-1) s.c.) reduced USVs but had no effects on locomotor behaviour or negative geotaxis. Lower doses of flibanserin (0.5, 1, 2 and 4 mg kg(-1) s.c.) had no effect on any behaviour. Diazepam (0.25, 0.5, 1 and 2 mg kg(-1) s.c.) not only reduced the USVs but also increased rolling and increased the latency of the negative geotaxic response. Imipramine (10, 15, 20 and 30 mg kg(-1) s.c.) reduced USVs, increased total locomotor activity and rolling but had no effect on negative geotaxis. None of the drugs altered body temperature. Our data showed that flibanserin is as effective in reducing the USVs as diazepam and imipramine but has a lower incidence of motor side effects. This suggests that flibanserin might be effective for the treatment of mood disturbances such as anxiety. (+info)
Participation of GABAergic and histaminergic systems in inhibiting amygdaloid kindled seizures.
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The effects of GABAmimetic drugs on inhibition of amygdaloid kindled seizures induced by clobenpropit were investigated to clarify the relationship between histaminergic and GABAergic systems in seizures. I.p. injection of clobenpropit caused dose-dependent inhibition of amygdaloid kindled seizures. GABAmimetic drugs such as diazepam, sodium valproate and muscimol also inhibited amygdaloid kindled seizures in a dose-dependent manner. Diazepam at doses of 0.2 and 0.5 mg/kg, which showed no significant effect on amygdaloid kindled seizures when used separately, significantly potentiated the effect of clobenpropit. Similar findings were observed with sodium valproate and muscimol at doses of 100 mg/kg and 5 ng, respectively, although neither showed any significant effects when administered separately. Bicuculline caused significant antagonism of the inhibition of amygdaloid kindled seizures induced by clobenpropit, while the effect of diazepam was not antagonized by diphenhydramine. These results suggested that inhibition of amygdaloid kindled seizures induced by histamine is closely associated with the actions of GABA. (+info)
Diazepam attenuation of somatostatin binding and effect of somatostatin on accumulation of inositol 1,4,5-trisphosphate in the rat frontoparietal cortex.
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Numerous reports in both humans and animals have confirmed that benzodiazepines produce amnesia; however, mechanisms mediating this effect are not clear. In view of the important role of brain somatostatin (SRIF) in the cognitive function of rats, this study sought to determine if the benzodiazepine, diazepam, alters somatostatinergic system in the rat frontoparietal cortex. Intraperitoneal (i.p.) administration of diazepam (5 mg/kg/day) to male Wistar rats (200-250 g) for 3 or 7 days decreased the number of SRIF receptors (26 and 37%, respectively) in synaptosomes from the frontoparietal cortex, without influencing their apparent affinity. This decrease in the tracer binding was not attributable to a direct effect of diazepam on SRIF receptors, because no decrease of SRIF binding was induced by a large concentration of diazepam (10(-4) M) when the drug was added to a preparation of synaptosomes from frontoparietal cortex of untreated rats. To determine if the effect of diazepam on SRIF binding is related to the binding of diazepam to its recognition site on the GABA(A) receptor, a benzodiazepine antagonist, 2-phenylpyrazolo[3,4-c]quinolin-3(5H)-one (CGS 8216) was administered before the diazepam injection. Pretreatment with CGS 8216 (20 mg/kg/day, i.p.) blocked completely the diazepam-induced decrease in the number of SRIF receptors. CGS 8216 alone had no observable effect. The decrease in the number of 125I-Tyr11-SRIF receptor induced by diazepam was accompanied by a decrease in the effect of SRIF, after 15 seconds of stimulation, on inositol 1,4, 5-trisphosphate (IP3) mass accumulation in the rat frontoparietal cortex at 3 (64%) or 7 days (59%) after its administration. Diazepam alone had no observable effect on mass accumulation of IP3. After 14 days of daily diazepam injections, the levels of binding of 125I-Tyr11-SRIF in the frontoparietal cortex returned to control values, coinciding with the tolerance that develops to this benzodiazepine agonists when administered chronically. The decrease in IP3 levels was still observed after 14 days (57%) diazepam administration. Diazepam and CGS 8216 did not affect SRIF-like immunoreactivity levels in the frontoparietal cortex at the three time intervals studied (3, 7 or 14 days). The alteration of frontoparietal cortex SRIF receptor-effector system after 3 or 7 days of diazepam treatment suggests that somatostatinergic neurotransmission plays a role in the mechanism of diazepam action on memory. (+info)