Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sleep apnea and PLMS are extremely prevalent in the elderly. The subjective reports of poor sleep, insomnia, snoring, and excessive daytime sleepiness should not be taken lightly and should not be assumed to be a normal sign of aging. These problems may be interrelated and may be symptoms of the sleep disorders discussed above. Physicians and gerontologists need to become more sensitive to the special problems and needs related to sleep disorders in the geriatric population.
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PMID:Epidemiology of sleep disorders. 266 16

The effect of zolpidem 10 mg p.o. on sleep in patients with persistent psychophysiological insomnia was assessed by polysomnographic recordings. An improvement in sleep with no rebound insomnia was observed during treatment for two weeks. Time awake after the onset of sleep was reduced after one week and increased after two weeks, whereas sleep latency remained reduced. Zolpidem markedly increased the duration of Stage 2 sleep without affecting either slow wave sleep or REM sleep. Subjective evaluation of improvement in sleep was well correlated with sleep laboratory findings. Zolpidem did not impair the immediate memory or psychomotor performance of patients on the morning after its administration. Side-effects during the period of drug administration included drowsiness, fatigue, headache, anxiety and irritability. They were mild or moderate and wore off soon after awakening.
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PMID:Effect of zolpidem on sleep in insomniac patients. 266 41

This study was undertaken to compare the effects of 0.25 mg of brotizolam, 15 mg of flurazepam, and placebo on the sleep and performance of elderly subjects with chronic insomnia during a 2-week period of administration. Thirty-six male and female subjects who ranged in age from 60-72 years were divided into three treatment groups. All groups received placebo on the first three study nights, the active drug or placebo on the next 14 nights, and placebo again on the two following withdrawal nights. Sleep was assessed by means of questionnaires, and residual effects during the day were studied by means of the multiple sleep latency test and a variety of memory, performance, and vigilance tests. Sleep improved with all treatments. Rebound insomnia was noted on brotizolam withdrawal; flurazepam withdrawal had a milder impact. At the end of this 19-night study, only the placebo-treated group was sleeping significantly longer than at baseline. Both drug treatments increased daytime sleepiness and impaired performance on the first day after their administration. These effects waned after 2 weeks of treatment with brotizolam, but not flurazepam. The results of this study affirm the increased sensitivity of elderly subjects to benzodiazepine hypnotics and their indication for acute or intermittent insomnia, rather than for the more chronic forms of this disorder.
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PMID:A comparative study on the effects of brotizolam and flurazepam on sleep and performance in the elderly. 267 Oct 59

Hexamethylene bisacetamide (HMBA), a potent differentiating agent, was administered to patients with refractory malignant tumors. Thirteen patients received 30 evaluable courses. HMBA was given by continuous i.v. infusion for 5 days. Therapy was repeated every 28 days, if patients had recovered from toxicity. The starting dose was 24 g/m2/day. Because our previous trial had shown wide interpatient variability in HMBA pharmacokinetics and excess toxicity at HMBA plasma concentrations greater than 2 mM (HMBA doses between 24 and 33.6 g/m2/day), we attempted to individualize each patient's dose based on a dosing scheme using an adaptive (feedback) control algorithm, which assumed linear clearance for HMBA. In all courses, a plasma sample was assayed daily and infusion rates were adjusted to achieve an HMBA plasma concentration of 1.5-2.0 mM (300-400 mg/liter). The patients included 12 men and 1 woman with a median age of 56 years (range, 34-76) and median Karnofsky performance status of 90% (range, 60-100). All patients had received prior chemotherapy and 9 patients had also received radiation therapy. The linear adaptive control algorithm was reasonably precise, with a mean absolute error of 0.28 (SE 0.04) mM. However, adjustments in infusion rate systematically overshot the desired change in steady state concentration, probably due to nonlinear clearance of HMBA. For levels within 24 h of a change in infusion rate, this resulted in significant bias, with a mean error of 0.24 (SE 0.09) mM. The mean absolute error was 0.40 (SE 0.06) mM. A second adaptive control algorithm, using a pharmacokinetic model with parallel first-order (renal) clearance and Michaelis-Menten (nonrenal) clearance and using Bayesian parameter estimation with a priori estimates based on our previous phase I trial, proved to be much more precise than the linear method and was unbiased when applied retrospectively to the same observations, with a mean error (within 24 h of a change in infusion rate) of 0.02 (SE 0.06) mM and a mean absolute error of 0.22 (SE 0.03) mM. Toxicity was reversible in all cases. Neurotoxicity, consisting of hallucinations, agitation, somnolence, or confusion, was seen in 2 patients. Four patients complained of insomnia or anxiety. Mild asymptomatic acidosis was seen in 3 patients. Other toxicity included grade 1-2 nausea and vomiting (10 patients), grade 2 diarrhea (2 patients), grade 3 thrombocytopenia (3 patients), grade 1-3 leukopenia (3 patients), and oral herpes simplex infection (4 patients). Mild reversible renal insufficiency (measured by creatinine clearance) was seen in 8 patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Phase I trial using adaptive control dosing of hexamethylene bisacetamide (NSC 95580). 272 Jun 96

1. This study presents the results of the preliminary screening of vigabatrin as add-on therapy in an open, non-controlled multicentre study in children with refractory epilepsy. 2. There were 135 children, with an age range of 2 months-12 years. Main seizure type was partial in 42%, generalized in 29%, Lennox-Gastaut syndrome in 19% and West syndrome in 10%. 3. Vigabatrin was added onto current antiepileptic treatment in an initially recommended dose of 40-80 mg kg-1 day-1. However, the doses were frequently increased when tolerance allowed it, and the final mean dose used was 87 mg kg-1 day-1 (27-600). 4. A 75% to 100% reduction in seizure frequency was observed in 25% of patients (11 patients became seizure free) and 50 to 75% decrease in a further 13%. Efficacy was better in partial seizures, with good to excellent results in 49% of patients. The use of high doses, above 100 mg kg-1 day, was not associated with greater efficacy in this preliminary study. 5. No side effects were reported in 79% of patients. Agitation and insomnia were observed in 8.8% and somnolence in 6%. Other adverse events included ataxia (2.2%), nausea (2.2%) and increased appetite (1%). A moderate and transient decrease in haemoglobin was reported in six patients from the same centre; these patients were all receiving very high doses of vigabatrin (250 to 600 mg kg-1 day-1). 6. Vigabatrin thus appears to be a safe antiepileptic drug that may be effective in the treatment of severe epilepsy in children.
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PMID:Vigabatrin in the treatment of epilepsy in children. 275 1

Acceptability and plasma concentrations of rilmenidine, a new antihypertensive agent mainly eliminated via the kidney, were evaluated in 17 hypertensive patients (supine diastolic blood pressure, 104 +/- 3 mmHg) with renal insufficiency (creatinine clearance, 35 +/- 4 ml.minute-1/1.73 m2; range, 12 to 58). Patients were treated for six months with rilmenidine at the dose of 1 mg in the morning or 1 mg twice daily as single-drug therapy in untreated patients, or in combination or as substitution in patients already treated. Plasma concentrations of rilmenidine were measured by gas chromatography combined with mass spectrometry at Days 0, 1, 5, 7, 9, and 11, and Months 1.5, 3, 4.5, and 6 before administration. Supine and erect blood pressure (sphygmomanometer) measurements and side effects were noted at the same times. Laboratory and electrocardiographic parameters were evaluated at Days 0 and 11, and Months 1.5 and 6. Blood pressure was effectively controlled during the trial in 12 patients (mean decrease in systolic/diastolic blood pressure of 12/8 mmHg). Five patients were removed from the trial after Month 1.5 because of a rise in blood pressure (three cases) or noncompliance (two cases). Side effects were moderate and transient (dry mouth, constipation, daytime drowsiness, mood disturbances, insomnia) never requiring treatment withdrawal. Surveillance of renal function revealed no significant mean variation. Rilmenidine plasma concentrations reached steady state the fifth day at the latest and were related to the degree of renal insufficiency. When renal function was stable (13 cases), plasma concentrations did not vary until the end of the trial. When renal function was progressive (four cases), plasma concentrations increased in parallel in two patients, without the onset of side effects, and remained stable in the other two patients. In conclusion, this study confirmed the good acceptability of rilmenidine in hypertensive patients with chronic renal insufficiency. It showed stable plasma concentrations of rilmenidine during a six-month treatment in hypertensive patients with renal insufficiency, reflecting the absence of accumulation of the drug.
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PMID:Acceptability of rilmenidine and long-term surveillance of plasma concentrations in hypertensive patients with renal insufficiency. 278 26

The author reviews the literature reporting the untoward effects of withdrawing monoamine oxidase inhibitors (MAOIs). The withdrawal of these agents can result in severe anxiety, agitation, pressured speech, sleeplessness or drowsiness, hallucinations, delirium and paranoid psychosis. MAOI withdrawal phenomena resemble the symptoms produced by the discontinuation of chronically administered psychostimulants. The capacity of MAOI to exert amphetamine-like effects presynaptically, and the propensity of somatic treatments for depression to subsensitize presynaptic receptors regulating the release of catecholamines, can provide a basis for the development of psychotic syndromes upon the withdrawal of MAOIs. Evidence for this hypothesis is reviewed.
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PMID:Monoamine oxidase inhibitor withdrawal phenomena: symptoms and pathophysiology. 284 11

Benzodiazepines currently represent the most widely prescribed family of hypnotic drugs. They possess obvious advantages: actual hypnotic efficacy, at least with short-term use, low toxicity, and excellent tolerance. However, several side effects need to be mentioned: besides morning drowsiness (which represents the untoward continuation of their sedative properties), anterograde amnesia, increase of daytime anxiety, and rebound insomnia. Moreover, benzodiazepines significantly modify several sleep parameters: they decrease slow wave sleep and delay the first period of REM sleep. Any hypnotic benzodiazepine should only be prescribed in case of actual need and after exclusion of non-pharmacologic means. The "softest" agent, at the lowest dose, and during the shortest period should always be preferred.
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PMID:[Benzodiazepines and sleep]. 286 71

Two benzodiazepine hypnotics, one with an intermediate elimination t1/2 (temazepam, 15 mg) and the other with a long t1/2 (quazepam, 15 mg), were evaluated in 22- night sleep laboratory studies. The effectiveness and side effects of these benzodiazepines were assessed during short- and intermediate term use. Subjects were also assessed for the presence of rebound insomnia after abrupt withdrawal. Quazepam, 15 mg, was significantly effective in improving sleep both with short- and intermediate-term use, but the effectiveness of temazepam was considerably less. Although temazepam was effective for maintaining sleep with short-term use, there was rapid development of tolerance for this effect with intermediate-term use. Temazepam did not produce any behavioral side effects during either drug condition. The only side effect associated with quazepam was a significant degree of daytime sleepiness. After its withdrawal, temazepam was associated with some sleep and mood disturbance on the first withdrawal night, whereas quazepam had carryover effectiveness.
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PMID:Quazepam and temazepam: effects of short- and intermediate-term use and withdrawal. 286 23

Insomnia is a disorder of initiation and maintenance of sleep that results in daytime somnolence. The differential diagnosis of the various forms of insomnia is based primarily on the history, including information from the sleeping partner. The possibility of underlying depression or sleep apnea must be given consideration in every patient with insomnia, because inappropriate therapy may be dangerous in these instances. In general, the benzodiazepines have supplanted the traditional hypnotics in the treatment of insomnia.
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PMID:Diagnosis and treatment of insomnia. 288 77


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