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Purchases of hypnotics, sedatives and minor tranquillizers among 2,566 individuals in the county of Jämtland, Sweden. A 6-year follow-up.

Data from a continuous recording of drug prescriptions to 16,600 individuals in the county of Jämtland, Sweden, revealed that 2,566 patients (15.5%) obtained prescriptions for hypnotics, sedatives and minor tranquillizers in 1970. Occasional use (one purchase only, Group A) was seen in 7.4% of the population, intermediate use (two to six purchases, Group B) in 6.9% whereas 1.2% were regular users (seven purchases or more, Group C). For each group as a whole there was 5 years later a highly significant intraindividual reduction in the purchases of these drugs as well as of other psychotropic drugs. In all groups 10-23% had increased their purchases, most of them insignificantly. Fifteen of 30 patients with a marked increase in consumption developed a regular purchase pattern, but signs of overuse or abuse were seen in only four persons. During the studied period the benzodiazepines increased their share of the total from 45 to 60%. Antihistamines also increased in all groups while the proportion of barbiturates and combined preparations decreased markedly.

Anti-Anxiety Agents↗

Effect of hypnotic sedation during percutaneous transluminal coronary angioplasty on myocardial ischemia and cardiac sympathetic drive.

Forty-six patients were randomized to receive drug (group 1) or hypnotic sedation (group 2) during percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery. Intracoronary and standard electrocardiograms were continuously registered, and heart rate spectral variability was studied. Normalized units of low- and high-frequency components and the ratio of low to high frequency were measured during balloon inflations. The ST segment shifted at the first balloon inflation from 0.02 +/- 0.01 to 0.09 +/- 0.6 mm in group 1 and from 0.02 +/- 0.08 to 0.1 +/- 0.6 in group 2 mm (p <0.05). In group 1, the low-frequency band and the ratio of low to high frequency increased significantly during the first balloon inflation (from 59 +/- 10 to 75 +/- 10 normalized units and from 2.4 +/- 1.4 to 7.3 +/- 4.7, respectively; p <0.001). The increase of the ratio of low to high frequency was significantly related to ST shift (r = 0.706; p <0.01). In contrast, no significant variation of spectral parameters was found in group 2. The increase in cardiac sympathetic activity associated with balloon inflation and myocardial ischemia during percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery was selectively eliminated by hypnosis but not by drug sedation.

Angioplasty, Balloon, Coronary↗

Liquid chromatographic-thermospray tandem mass spectrometric quantitative analysis of some drugs with hypnotic, sedative and tranquillising properties in whole blood.

Results are presented of a liquid chromatographic-thermospray tandem mass spectrometric method of analysing different drugs in whole blood. Substances with hypnotic, sedative and tranquillising properties from the benzodiazepine, the thioxanthene, the butyrophenone, the methadone and the diphenylbutylpiperidine groups were investigated. It appears that ten to hundred times lower detection limits for the substances in whole blood can be reached with this method compared with methods more commonly used. Detection limits in the range 10-100 pg per injection (equivalent to 0.05-0.5 ng/ml whole blood) were reached for the majority of the compounds.

Benzodiazepines↗

Receptor subtype and dose dependence of dexmedetomidine-induced accumulation of [14C]glutamine in astrocytes suggests glial involvement in its hypnotic-sedative and anesthetic-sparing effects.

Dexmedetomidine, a selective alpha(2)-adrenergic agonist, increases accumulation of [14C]glutamine and its labeled metabolites in primary cultures of mouse astrocytes. The concentration dependence is biphasic and identical to that previously described for dexmedetomidine's effect on free cytosolic calcium concentration ([Ca(2+)](i)) in astrocytes, and both effects are exerted on the alpha(2A) subtype of the alpha(2) receptor, suggesting a Ca(2+)-mediated effect. The concentration corresponding to the most potent effect is similar to that with which dexmedetomidine exerts its anesthetic-sparing activity in vivo, and the second peak corresponds to its hypnotic-sedative effect. It is suggested that both effects may be caused by decreased glutamatergic neurotransmission, secondary to reduced availability of glutamine as a glutamate precursor in glutamatergic neurons.

Anesthetics↗

Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation.

The combination of haloperidol, 5 mg, and lorazepam, 4 mg, was both effective and safe for managing agitated behavior in an open trial with acutely psychotic patients. The combination also appeared to be superior to its individual components when studied in a randomized, nonblind trial. The principle of the combined use of antipsychotics and sedative-hypnotics was further tested by comparing two new combinations: thiothixene, 5 mg, and lorazepam, 4 mg, versus haloperidol, 5 mg, and phenobarbital sodium, 130 mg. These combinations had comparable efficacy and safety, and the level of transquilization approached that produced by the haloperidol-lorazepam combination in the preceding studies.

Adolescent↗

Synthesis and hypnotic-sedative activities of N-substituted uracil on mice.

N3-Phenacyl-N1-substituted uracils 3a-q were synthesized by introduction of substituents at the N1-position of N3-phenacyluracil 2, and their hypnotic and sedative activities were evaluated. Pharmacological activities of these N3-phenacyl-N1-substituted uracils were examined using hypnotic activity and synergistic effects with pentobarbital or diazepam for the hypnotic and sedative activities.

Animals↗

Dependence on sedative-hypnotics: neuropsychological impairment, field dependence and clinical course in a 5-year follow-up study.

Despite some neuropsychological improvement in a group of 30 patients who had been hospitalized for primary abuse of sedatives or hypnotics 4-6 years earlier, the prevalence of intellectual impairment was still increased and about as high as before. As in alcoholic patients CAT scan of the brain showed an increased prevalence of dilatation of the ventricular system, but unlike alcoholics not of widened cortical sulci. Field dependence and visuo-spatial skills during treatment predicted abuse status at follow-up. Patients with improved drug habits had less pronounced withdrawal symptoms during treatment and a better social situation at follow-up than patients without improvement of drug habits. The results suggest that despite some neuropsychological improvement cerebral disorder diagnosed in patients abusing sedatives or hypnotics is often permanent through the years and that neuropsychological status is linked to long-term prognosis.

Adult↗

Prostaglandin synthetase inhibitors antagonize hypothermia induced by sedative hypnotics.

Previous studies in our laboratory have demonstrated that inhibition of prostaglandin biosynthesis through pretreatment with aspirin and other prostaglandin synthetase inhibitors (PGSI) significantly reduces CNS sensitivity to a hypnotic dose of ethanol. Indomethacin, a potent PGSI, was administered to male LS, SS, and HS/Ibg mice (65 +/- 10 days of age) 15 min prior to administration of a hypnotic dose of ethanol or pentobarbital. Doses of indomethacin used were identical to those previously reported as optimally antagonizing ethanol-induced sleep. Another group received a vehicle-control injection, while a third group also received a control injection, but were placed in a incubator maintained at 30 +/ 1 degrees C. Body temperatures were recorded periodically for several hours. Both indomethacin and incubation significantly reduced hypothermia induced by ethanol and pentobarbital. Incubation increased sleep time after ethanol, but did not affect pentobarbital sleep time. These results suggest that the hypnotic and hypothermic effects of ethanol, although possibly mediated through prostaglandins, apparently are not causally linked.

Body Temperature↗

Ethanol, sedative hypnotics, and glutamate receptor function in brain and cultured cells.

Ethanol, acutely, is a potent and selective inhibitor of the function of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in primary cultures of cerebellar granule cells. The effect of ethanol can be reversed by high concentrations of glycine, and nonequilibrium ligand binding studies in brain membrane preparations suggest that ethanol may act by decreasing the frequency of ion channel opening. After chronic consumption of ethanol by animals, the number of NMDA receptors (measured by ligand binding) is increased in many brain areas. Similarly, NMDA receptor function is increased in cerebellar granule cells exposed chronically to ethanol. In the intact animal, this receptor up-regulation may be associated with ethanol withdrawal seizures, which are attenuated by uncompetitive antagonists at the NMDA receptor. In contrast to ethanol, barbiturates have a greater inhibitory effect at the kainate subtype of glutamate receptor than at the NMDA receptor. After chronic barbiturate ingestion, kainate binding is decreased in certain brain areas, while ligand binding to the NMDA receptor is increased. Overall, the pattern of brain area-specific effects of barbiturates on NMDA and kainate receptor function is quite distinct from that of ethanol.

Alcoholism↗