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)

A middle aged man who inhaled sarin in a train in a subway station in Tokyo in 1995 and showed a variety of symptoms including psychiatric symptoms was reported. He experienced muscle weakness, dyspnea and unconsciousness of sudden onset immediately after exposure to sarin. Marked miosis was observed on admission. Plasma cholinesterase activity was remarkably decreased at that time. He also experienced delirium consisting of visual hallucination, insomnia and irritability at mid-night for more than seven days. These psychiatric symptoms gradually improved without any medication. To date there is no detailed description of such psychiatric symptoms in sarin poisoning.
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PMID:[Psychiatric symptoms following accidental exposure to sarin--a case report]. 852 73

In order to clarify the later sequelae of sarin poisoning that occurred in Matsumoto City, Japan, on June 27, 1994, a cohort study was conducted on all persons (2052 Japanese people) inhabiting an area 1050 meters from north to south and 850 meters from east to west with the sarin release site in the center. Respondents numbered 1237 and 836 people when surveys were conducted at one and three years after the sarin incident, respectively. Numbers of persons with symptoms of sarin toxicity were compared between sarin victims and non-victims. Of the respondents, 58 and 46 people had symptoms associated with sarin such as fatigue, asthenia, shoulder stiffness, asthenopia and blurred vision at both points of the survey, respectively. The prevalences were low; some complained of insomnia, had bad dreams, difficulty in smoking, husky voice, slight fever and palpitation. The victims who had symptoms one year after the incident had a lower erythrocyte cholinesterase activity than did those who did not have symptoms at the early stage; such persons lived in an area with a 500 meter long axis north east from the sarin release site. The three-year cohort study clearly showed that the odds ratios of almost all of the symptoms were high in the sarin-exposed group, suggesting a positive relationship between symptoms and grades of exposure to sarin. These results suggest that symptoms reported by many victims of the sarin incident are thought to be sequelae related to sarin exposure.
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PMID:Sequelae of sarin toxicity at one and three years after exposure in Matsumoto, Japan. 1061 67

Donepezil is an acetylcholinesterase inhibitor indicated for the symptomatic treatment of mild to moderate Alzheimer's disease. It is reported to have a relatively favourable side-effect profile. We report here on a pharmacovigilance study carried out post-marketing in England. An observational cohort study using the technique of Prescription-Event Monitoring was carried out. Some 1762 patients (mean age 72.9 years; 42% male) were followed up for 6 months minimum. The commonest adverse events were nausea, diarrhoea, malaise, dizziness and insomnia. Aggression, agitation and abnormal dreams were uncommonly associated with the drug. There were no cardiac rhythm disturbances or liver disorders causally associated. The commonest adverse drug reactions are already reported in the product information. Given the relatively small size of this cohort, the signals of abnormal dreams and psychiatric disturbance as possible adverse drug reactions need further investigation in carefully planned studies.
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PMID:Adverse effects associated with the use of donepezil in general practice in England. 1119 60

Exposure to organophosphates (OP) has been associated with sleep disorders such as insomnia and "excessive dreaming." The central mechanisms of these effects are not well understood. OPs inhibit acetylcholinesterase (AChE) activity, leading to a hyperactivity of the brain cholinergic systems that are involved in sleep regulation. We studied alterations in the EEG, behavioral states, motor activity and core temperature in rats orally administered with 10 or 40 mg/kg of the OP insecticide chlorpyrifos (CHP). Occipital EEG, motor activity and core temperature were recorded with telemetric transmitters. Behavioral sleep-wake states were visually scored. Both doses of CHP produced alterations of the EEG (decrease in power of sigma/beta and increase in slow theta and fast gamma bands) characteristic of arousal. EEG alterations were consistent with behavioral changes such as an increase in wakefulness and a decrease in sleep. Waking immobility was a prevalent behavior. We did not detect any overt signs of CHP toxicity, such as an abnormal posture or gait, suggesting that reduced locomotion can be a result of central effects of CHP (such as activation of cholinergic motor inhibitory system) rather than peripheral (such as an impairment of neuromuscular function). Changes in the EEG and behavior occurred independently of the decrease in core temperature. Increased wakefulness together with reduced motor activity after exposure to CHP seems to be a result of hyperactivity in brain cholinergic neuronal networks.
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PMID:EEG spectra, behavioral states and motor activity in rats exposed to acetylcholinesterase inhibitor chlorpyrifos. 1217 64

This article reviews the piperidine derivative, donepezil hydrochloride (E2020, Aricept), a reversible central acetylcholinesterase inhibitor currently approved for treatment of mild-to-moderate Alzheimer's disease. Donepezil is well absorbed orally, unaffected by food or by time of administration; it reaches therapeutic levels in doses of 5-10 mg/day and peak plasma concentrations are obtained 3-4 h after oral administration. A single bedtime dose is recommended due to the long elimination half-life of the drug (70 h). Donepezil does not cause liver toxicity or significant drug interactions and is relatively well-tolerated. Initial side effects include nausea, vomiting, diarrhoea, insomnia, muscle cramps, fatigue, anorexia and syncope. Caution is advised in patients with bradycardia. Long-term use of donepezil in AD has been found to delay nursing-home placement and to result in caregiver respite. Donepezil also slows deterioration of cognition and global function in patients with moderate-to-severe AD, with improvement of abnormal behaviours. In addition to AD, donepezil demonstrates significant improvement in cognition, global function and activities of daily living in comparison with placebo-treated patients with vascular dementia and has potential therapeutic benefit for other neurological conditions.
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PMID:Donepezil: a clinical review of current and emerging indications. 1468 Apr 45

Patients with dementias, such as Alzheimer's disease (AD), often have nocturnally disrupted sleep. Clinically, this may present as agitation during the nighttime hours, which may affect as many as a quarter of AD patients during some stage of their illness. Sleep disturbance in AD may be multifactorial and involve sleep-disordered breathing and disrupted chronobiology, both often characterized by excessive daytime napping. Polysomnographically, AD patients show decreased rapid eye movement (REM) sleep in proportion to the extent of their dementia; some evidence suggests that cholinesterase inhibitors, commonly used pharmacologic agents for cognitive loss in AD, may increase REM sleep measures. Unfortunately, such agents may also induce insomnia and vivid dreams. There have been no randomized clinical trials of sedative-hypnotic medications specifically targeted at AD patients with sleep problems. Evidence suggests that sedative-hypnotics, such as benzodiazepine site-specific agonists, may have a role in some cases, whereas atypical antipsychotics may be necessary in other cases. There are also reports of successful interventions with nonpharmacologic options (eg, exercise, illumination). The utility of melatonin as a hypnotic in this population appears equivocal.
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PMID:Sleep disorders in Alzheimer's disease and other dementias. 1525 36

Daytime sedation is a common and potentially dose-limiting side effect of the opiate analgesics. The psychostimulants, such as methylphenidate, are frequently prescribed to treat this problem, but their use may be limited by side effects, such as weight loss, anxiety, or insomnia, or tolerance to their antisedative effects. Medications which enhance intracerebral cholinergic activity may offer an alternative treatment approach, since functional deficits of acetylcholine may, in part, account for the sedative and mind-dulling effects of opiates. Preliminary studies with donepezil, a centrally acting acetylcholinesterase (AChE) inhibitor approved for use in Alzheimer's disease, have suggested at least short-term benefit in treating opiate-related sedation. In a retrospective study, we reviewed the results of donepezil treatment in 40 patients, 37 of whom had cancer, which in most cases was in an advanced stage. All patients were receiving chronic opiate treatment, and the majority were on a stable opiate dose in the 2 weeks preceding the initiation of donepezil. The average opiate dose was 844 mg in oral morphine equivalents. Seventy-three percent of the patients experienced moderate or greater improvement on the Clinical Global Improvement Scale. Evaluations on the Epworth Sleepiness Scale (ESS; 0-24), visual analog sleepiness scale (VAS; 0-100), and average pain levels (0-100), before and after donepezil treatment, were obtained on 19 patients. Prior to donepezil, ESS, VAS, and pain scores were 18.5, 76.3, and 47.4. After an average of 21 days of donepezil treatment, scores were 9.5 (P < 0.001), 39.5 (P < 0.001), and 36.6 (P = 0.07), respectively. The mean total duration of treatment for patients was 54.4 days, with most patients stopping donepezil due to progression to a terminal state. Patients were generally started on 5 mg/ day, but 17 patients required higher doses to achieve or maintain efficacy, the average treatment dose being 9.13 mg/day. We concluded from this study that centrally acting AChE inhibitors are promising agents in the treatment of sedation,and perhaps of other neuropsychological side effects associated with the use of opiate analgesics.
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PMID:Treatment of opiate-related sedation: utility of the cholinesterase inhibitors. 1535 44

Cholinesterase (ChE) inhibitors, which prevent the hydrolysis of acetylcholine, have been approved for the symptomatic treatment of Alzheimer's disease (AD) for over a decade. However, the first ChE inhibitors were associated with a high incidence of side-effects and general tolerability concerns, including hepatotoxicity. Side-effects associated with increased cholinergic activity, particularly in the gastrointestinal (GI) system, can prevent patients from achieving effective doses of drug. In addition, the advanced age and frail nature of patients with AD mean that poor tolerability is a serious concern. The potential for drug-drug interactions is also an important consideration, due to the high prevalence of comorbid disease in these patients. Data both from clinical trials and studies in routine clinical practice have shown that donepezil is associated with a low incidence of GI adverse events (AEs) that is comparable with placebo. Donepezil is a potent, selective inhibitor of acetylcholinesterase, and selective inhibition of central as opposed to peripheral ChEs might be expected to reduce the incidence of AEs, thus this may explain the lower incidence of cholinergic AEs observed following treatment with donepezil, compared with nonselective ChE inhibitors. There are no differences in cardiovascular AEs, including bradycardia, between placebo and donepezil groups in the clinical trials published to date, even in a very sick vascular dementia population with high rates of comorbidity and concomitant medication use. Data from single- and multiple-dose studies of donepezil in patients with hepatic impairment and with moderately to severely impaired renal function indicate that donepezil is safe and well tolerated in these groups. Furthermore, both in vitro and clinical studies have shown that donepezil is not associated with drug-drug interactions. The incidence of weight loss is very similar between donepezil- and placebo-treated patients. Although insomnia and other sleep disorders have been reported following administration of donepezil, lengthening the time period before increasing the dose of donepezil from 5 to 10 mg day(-1) or switching to morning dosing can reduce these events to the levels of placebo-treated patients. Over 770 million days of patient use and an extensive publication database demonstrate that donepezil has a good tolerability and safety profile.
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PMID:The safety and tolerability of donepezil in patients with Alzheimer's disease. 1549 17

The neuropsychiatry of Parkinson's disease (PD) and its correlates are reviewed. Dementia occurs in up to 30% and can be treated with cholinesterase inhibitors. Cognitive impairments involve executive, visuospatial, attentional, and memory dysfunctions. Apathy may respond to dopamine agonists or cholines-terase inhibitors. Cognitive impairment, psychosis, and depression predict quality of life. Visual hallucinations and paranoia are common, and respond to low dose clozapine. Depression is common and predicts caregiver burden and depression. The best data suggest the efficacy of nortriptyline and the safety of SSRIs. Anxiety disorders occur in 40% of patients, especially off-period panic attacks and specific phobias. Bromazepam has proven useful for anxiety in PD, but buspirone has only diminished drug-induced dyskinesias to date. Sleep disorders occur in up to 94% of patients. Insomnia is common and is treated by dopaminergic agent dose reduction, nocturnal dosing, treatment of depression, or use of short half-lived hypnotics, depending on etiology. Parasomnias include REM behavior disorder and vivid dreams and nightmares. Excessive daytime somnolence occurs in at least 15% of patients. Sleep attacks are common and patients should be warned about driving when taking dopamine agonists. Sexual disorders occur in most patients. Paraphilias are associated with dopamine agonists, and clozapine may be useful in their treatment. Surgical therapies are associated with a wide variety of neuropsychiatric features, and vigilance for suicide attempts with subthalamic nucleus stimulation seems warranted. Neuropsychiatric disorders are important determinants of quality of life and caregiver burden in PD. More clinical research is needed to establish effective treatments.
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PMID:The neuropsychiatry of Parkinson's disease. 1617 59

Delayed disease progression and symptomatic improvement occur with cholinesterase inhibitors (ChEIs) in dementia with Lewy bodies (DLB). In this study, complications (insomnia, dyskinesias, agitation, and delirium) occurred in three patients switched from donepezil to galantamine. The authors describe evidence-based recommendations for ChEI switchover in DLB.
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PMID:Emergent complications following donepezil switchover to galantamine in three cases of dementia with Lewy bodies. 1638 98


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