Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients with Parkinson's disease (PD) disturbances of mental state constitute some of the most difficult treatment challenges of advanced disease, often limiting effective treatment of motor symptoms and leading to increased disability and poor quality of life. This article provides an update on the current knowledge of these complications and the use of old and new drugs in their management. Mental state alterations in PD include depression, anxiety, cognitive impairment, apathy, and treatment-related psychiatric symptoms. The latter range from vivid dreams and hallucinations to delusions, manic symptoms, hypersexuality, dopamine dysregulation syndrome and delirium. While some of these symptoms may be alleviated by anti-parkinsonian medication, especially if they are off-period related, treatment-related phenomena are usually exacerbated by increasing the number or dosage of antiparkinsonian drugs. Elimination of exacerbating factors and simplification of drug regimes are the first and most important steps in improvement of such symptoms. However, the advent of atypical antipsychotics such as clozapine has dramatically helped the management of treatment-related psychiatric complications in PD. In patients with dementia associated with PD cognitive functioning and behavioural problems appear to respond to cholinesterase inhibitors, such as rivastigmine or donepezil. Depression is a common problem in early as well as advanced PD, and selective serotonin reuptake inhibitors, reboxetine, and tricyclic antidepressants have been reported to be effective and well tolerated antidepressants. Randomised, controlled studies are required to assess the differential efficacy and tolerability of antidepressants in patients with PD, including the newer antidepressants with serotonergic and noradrenergic properties.
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PMID:Psychiatric aspects of Parkinson's disease--an update. 1525 80

Delirium is commonly encountered in elderly patients in general hospitals. Most patients with delirium respond well within 12 days of commencement of treatment with haloperidol. A significant number of patients, however, does not improve. Three elderly male patients aged 85, 79 and 81 respectively suffering from prolonged delirium and unresponsive to haloperidol or atypical anti-psychotic drugs, responded well within days to treatment with rivastigmine--a cholinesterase-inhibitor. It was very well tolerated. In The Netherlands cholinesterase inhibitors are registered for the symptomatic treatment of Alzheimer's disease. There is some evidence, both from animal and human experiments, that cholinergic deficiency plays a role in certain types of delirium. Therefore treatment of delirium with a cholinesterase-inhibitor seems logical. Controlled studies are needed to evaluate the effects of these types of drugs in patients with prolonged delirium.
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PMID:[Successful treatment of three elderly patients suffering from prolonged delirium using the cholinesterase inhibitor rivastigmine]. 1555 63

Charles Bonnet syndrome (CBS) is characterized by the presence of complex visual hallucinations in psychologically normal people. Although visual hallucinations in the elderly are often associated with dementia with Lewy body (DLB), Alzheimer's disease and delirium, they are excluded from the diagnosis of typical CBS, as are cognitive or psychiatric disturbances, sleep disorders and focal neurological lesions. Here, we describe a patient with typical CBS, who responded to donepezil, a cholinesterase inhibitor, and has not shown any symptoms suggestive of Alzheimer's disease or DLB for approximately the past 40 months. However, follow-up examination of her clinical symptoms is necessary for a definite exclusion of Alzheimer's disease and DLB. The effectiveness of donepezil indicates that the patient's visual hallucinations might be related to dysfunction of cholinergic neurones, although she did not exhibit any cognitive decline, or morphological and physiological brain pathology. Because donepezil has fewer adverse effects than anticonvulsants and neuroleptic drugs, it may be a safer option for the treatment of CBS in the elderly.
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PMID:Treatment of typical Charles Bonnet syndrome with donepezil. 1548 23

The goal of this study was to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), has any effect on delirium in vascular dementia (VaD). The results from this follow-up study suggest that although delirium is frequent in elderly, cognitively impaired patients, it might not be a simple consequence of acute disease and hospitalization. Rather, delirium can be secondary to brain damage and to metabolic disturbances. According to the Lewy body dementia model, delirium could be induced by a lack of acetylcholine in the brain. Rivastigmine may help reduce the frequency of delirium episodes and help shorten their duration. Additional studies are required to better define the causes of delirium, which currently has no definitive treatment.
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PMID:Cholinesterase inhibition as a possible therapy for delirium in vascular dementia: a controlled, open 24-month study of 246 patients. 1563 41

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

More than 50% of people with dementia experience behavioral and psychological symptoms of dementia (BPSD). BPSD are distressing for patients and their caregivers, and are often the reason for placement into residential care. The development of BPSD is associated with a more rapid rate of cognitive decline, greater impairment in activities of daily living, and diminished quality of life (QOL). Evaluation of BPSD includes a thorough diagnostic investigation, consideration of the etiology of the dementia, and the exclusion of other causes, such as drug-induced delirium, pain, or infection. Care of patients with BPSD involves psychosocial treatments for both the patient and family. BPSD may respond to those environmental and psychosocial interventions, however, drug therapy is often required for more severe presentations. There are multiple classes of drugs used for BPSD, including antipsychotics, anticonvulsants, antidepressants, anxiolytics, cholinesterase inhibitors and NMDA modulators, but the evidence base for pharmacological management is poor, there is no clear standard of care, and treatment is often based on local pharmacotherapy customs. Clinicians should discuss the potential risks and benefits of treatment with patients and their surrogate decision makers, and must ensure a balance between side effects and tolerability compared with clinical benefit and QOL.
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PMID:Management of the behavioral and psychological symptoms of dementia. 1822 62

There is a wide variation and lack of evidence in current recommendations for atropine dosing schedules leading to subsequent variation in clinical practice. Therefore, we sought to examine the safety and effectiveness of a titrated vs. ad hoc atropine treatment regimen in a cohort of patients with acute cholinesterase inhibitor pesticide poisoning. A prospective cohort study was conducted in three district secondary referral hospitals in Sri Lanka using a structured data collection form that collected details of clinical symptoms and outcomes of cholinesterase inhibitor pesticide poisoning, atropine doses, and signs of atropinization. We compared two hospitals that used a titrated dosing protocol based on a structured monitoring sheet for atropine infusion with another hospital using an ad hoc regime. During the study, 272 symptomatic patients with anticholinesterase poisoning requiring atropine were admitted to the three hospitals. Outcomes of death and ventilation were analyzed for all patients, 226 patients were prospectively assessed for atropine toxicity. At baseline, patients in the titrated dose cohort had clinical signs consistent with greater toxicity. This in part may be due to ingestion of more toxic organophosphates. They received less pralidoxime and atropine, and were less likely to develop features of atropine toxicity, such as delirium (1% vs. 17%), hallucinations (1% vs. 35%), or either (1% vs. 35%) and need for patient restraint (3% vs. 48%) compared with the ad hoc dose regime. After adjusting for the pesticides ingested, there was no difference in mortality and ventilatory rates between protocols. Ad hoc high dose atropine regimens are associated with more frequent atropine toxicity without any obvious improvement in patient outcome compared with doses titrated to clinical effect. Atropine doses should be titrated against response and toxicity. Further education and the use of a structured monitoring sheet may assist in more appropriate atropine use in anticholinesterase pesticide poisoning.
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PMID:Comparison of two commonly practiced atropinization regimens in acute organophosphorus and carbamate poisoning, doubling doses vs. ad hoc: a prospective observational study. 1878 5

Dementia with Lewy bodies is one of the most common dementias in the elderly after Alzheimer's disease. It can be recognized on the basis of several clinical characteristics including progressive dementia with marked slowing and fluctuations, persistent visual hallucinations and an extrapyramidal syndrome. Several other clinical and imaging features are highly suggestive such as the presence of rapid eye movement sleep disorder, severe sensitivity to neuroleptics and specific neuroimaging abnormalities. Therapeutic strategies include prescription of L-dopa and cholinesterase inhibitors such as rivastigmine, and avoidance of anticholinergic medications and neuroleptics. Physicians who care for older people should have a heightened awareness of this entity in order to diagnose it early, avoid mistaking it for delirium and initiate appropriate treatment.
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PMID:Dementia with Lewy bodies: clinical diagnosis and therapeutic approach. 1918 68

Delirium is characterized by disturbances of consciousness, attention, cognition, perception, emotions, sleep, and psychomotor activity. Management of delirium involves ensuring safety, improving functioning, identifying and treating the illness underlying the delirium, and use of antipsychotics or benzodiazepines to control behavioural symptoms and prevent mortality. Haloperidol continues to be the most commonly used antipsychotic in delirium. However, in recent times data have emerged which suggest that atypical antipsychotics may be as efficacious as haloperidol in the treatment of delirium. This review intends to review the data with respect to usefulness of atypical antipsychotics in the treatment of delirium. Besides atypical antipsychotics, data with respect to another group of medications - cholinesterase inhibitors are also reviewed. Electronic and manual searches were conducted to identify all the relevant studies and case reports/case series. Evidence suggests that risperidone, olanzapine and quetiapine are as efficacious as haloperidol in the treatment of delirium but have lesser side effects. Data for other atypical antipsychotics are scarce. The data on cholinesterase inhibitors for treatment and prevention of delirium are beginning to accumulate, but do not seem to be convincing. Our review suggests that risperidone, olanzapine and quetiapine are good alternatives to haloperidol in the treatment of delirium.
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PMID:Usefulness of atypical antipsychotics and choline esterase inhibitors in delirium: a review. 2217 27

Dementia with Lewy-bodies (DLB) and Parkinson's disease dementia (PDD) are no rare causes of dementia. Both have neuropathologically, clinically, and neurochemically much in common. In the course of both conditions frequently psychotic symptoms occur, often induced by antiparkinsonian medication. Treatment of psychotic features with conventional antipsychotics is not tolerated in many cases. Therefore low-dose clozapine treatment is acknowledged usual practise for psychosis in Parkinson's disease and a case report indicates efficacy for psychosis in DLB, too. All other atypical antipsychotics except risperidone are not licensed for dementia in Germany, but risperidone is contraindicated in DLB due to manufacturer's notice and usually not well tolerated in DLB and Parkinson's disease. Open trials indicate safety for treatment of psychosis in DLB and PDD with quetiapine. Randomized controlled trials indicate, that quetiapine is less effective than clozapine against psychotic symptoms in both conditions, although comparatively safe. Cholinesterase inhibitors, especially rivastigmine, are a therapeutic alternative for treating both psychotic and cognitive symptoms in both conditions. Parkinsonism in DLB-patients responds worse to levodopa compared to patient with Parkinson's disease. Anticholinergic drugs often induce delirium in demented patients and therefore should be avoided. The same problem is associated with dopamine agonists in PDD and DLB. Amantadine, a NMDA-receptor antagonist like memantine, potentially bears the same risk of worsening psychotic symptoms. The following preliminary recommendation for drug treatment of PDD and DLB can be given: Stop all anticholinergic medication and reduce levodopa and other antiparkinsonian medication to the tolerated minimum. Levodopa alone is preferred. Treat with cholinesterase inhibitors to the maximum tolerated dose. If there is no adequate response regarding psychotic symptoms, add quetiapine. If this approach fails, replace quetiapine by low-dose clozapine. If behavioural disturbances are due to depression, anxiety, or irritability, treatment with an antidepressant, preferably citalopram, is an option.
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PMID:[Drug treatment of dementia with Lewy bodies and Parkinson's disease dementia--common features and differences]. 2142 15


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