Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caregivers play a determining role in choosing treatments for persons with Alzheimer's disease. The objective of this study was to examine caregivers' willingness to have persons with Alzheimer's disease continue taking cholinesterase inhibitors in the event that any 1 of 11 adverse effects was to occur. Data were gathered via postal questionnaire from 375 caregivers in Montreal. Sixty-four per cent of caregivers responded ( n = 201), and most (> or =59%) were willing to continue treatment if persons with Alzheimer's disease suffered from weight loss or loss of appetite. However, most (> or =53%) were not willing to continue treatment in the event of headache, dizziness, nausea, diarrhea, vomiting, drop in blood pressure, insomnia, muscle cramps, or stomach bleeding. The use of cholinesterase inhibitors by persons with Alzheimer's disease was positively associated with caregivers' willingness to accept greater numbers of adverse effects (adjusted relative risk = 1.97; 95% CI = 1.11 to 3.61). Caregivers appear to make a risk-benefit assessment when they decide whether or not care-recipients should continue pharmacotherapy in the event of adverse effects.
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PMID:Caregiver acceptance of adverse effects and use of cholinesterase inhibitors in Alzheimer's disease. 1823 27

The serotonin transporter protein (SERT) has been the target for the development of several modern antidepressants with an objective of achieving selectivity over other monoamine transporters, thereby minimising side effects observed in the older generation of tricyclic antidepressants. The clinical selective serotonin reuptake inhibitors (SSRIs) have been shown to be among the most effective therapies in the treatment of depression. However they have clinical disadvantages over other classes of antidepressant drugs such as slow onset of action nausea and sleep disruption. The negative feedback loop attributed to the presynaptic 5-HT(1A) receptors has been implicated in the "time lag" observed in many patients between the administration of the SSRI and its observed therapeutic action. In recent years the focus has been on developing compounds with dual affinity for serotonergic auto-receptors along with an inhibitory activity at SERT. These structurally diverse products promise to be the next generation of anti-depressant medicines. This review presents an analysis of the recently reported structural classes with SSRI activity and rationalises the unique relationship between their molecular properties and biological activities. Specific emphasis is placed on the development of molecular structures with dual serotonergic activity. Recent advances in the design and synthesis of single molecular entities possessing 5-HT reuptake inhibition together with 5-HT(1A), 5-HT(1B), 5-HT(1D), 5-HT(2A), DAT, NET, alpha (2)-adrenoceptor and acetylcholinesterase antagonism are reviewed. The structural studies to identify proposed SERT binding sites together with the role of structure and ligand based design in the development of more effective SSRIs are summarised.
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PMID:Recent developments in the design of anti-depressive therapies: targeting the serotonin transporter. 1867 23

The aim of this review is to describe side effects of five antidementives which are approved by the United States Food and Drug Administration (FDA); four acetylcholinesterase inhibitors and one glutamate - or N-metyl-D-aspartat receptor antagonist - memantine. The antidementives are well tolerated and undesired effects are rare; except hepatotoxicity of tacrine and gastrointestinal side effects of donepezil, rivastigmine, galantamin and tacrine that result from acetylcholinesterase inhibition. Nausea, diarrhea, vomiting, and weight loss are the most common side effects of the acetylcholinesterase inhibitors. Significant cholinergic side effects can occur in patients receiving higher doses; often they are related to the rate of initial titration of medication. Memantine is the first noncholinesterase inhibitor indicated for Alzheimer's disease. The side effects which may occur during the treatment with memantine are constipation, dizziness, headache and confusion. These effects if appears are mild end transient.
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PMID:Side effects of approved antidementives. 1927 Jun 33

Trichlorfon (o-o-dimethyl-2,2,2-trichloro-hydroxyethylphosphate), an organophosphate, has a moderately potent anticholinesterase activity. Organophosphate poisoning is well known for its characteristic symptoms and signs, but acute hemolysis caused by trichlorfon is rarely reported. We present a patient who developed acute hemolysis and renal function impairment after percutaneous trichlorfon exposure. A 54-year-old man applied trichlorfon powder to his dog to kill its parasites. Half an hour later, the dog was suspected to die of cholinergic crisis and the patient felt abdominal cramping pain. Later, he developed severe nausea, vomiting, chills, high fever, and cold sweat. Laboratory work-up disclosed a picture of acute hemolysis, jaundice, renal function impairment and leukocytosis. However, there were no clinical features of acute cholinergic syndrome except gastrointestinal symptoms, and blood cholinesterase activities were also normal. He eventually had a full recovery. Trichlorfon should be added to the toxins known to cause acute hemolysis.
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PMID:Acute hemolysis caused by incidental trichlorfon exposure. 1937 80

Malathion is an organophosphate pesticide that is known for its high toxicity to insects and low to moderate potency to humans and other mammals. Its toxicity has been associated with the inhibition of acetylcholinesterase activity, leading to the interference with the transmission of nerve impulse, accumulation of acetylcholine at synaptic junctions, and subsequent induction of adverse health effects including headache, dizziness, nausea, vomiting, bradycardia, and miosis. Oxidative stress (OS) has been reported as a possible mechanism of malathion toxicity in humans. Hence, the aim of this study was to examine the role of OS in malathion-induced cytotoxicity and genotoxicity. To achieve this goal, MTT, lipid peroxidation, and single cell gel electrophoresis (Comet) assays were performed, respectively, to evaluate the levels of cell viability, malondialdehyde (MDA) production, and DNA damage in human liver carcinoma (HepG(2)) cells. Study results indicated that malathion is mitogenic at lower levels of exposure, and cytotoxic at higher levels of exposure. Upon 48 h of exposure, the average percentages of cell viability were 100% +/- 11%, 117% +/- 15%, 86% +/- 15%, 35% +/- 9%, and 27% +/- 7% for 0, 6, 12, 18, and 24 mM, respectively. In the lipid peroxidation assay, the concentrations of MDA produced were 12.55 +/- 0.16, 20.65 +/- 0.27, 31.1 +/- 0.40, 34.75 +/- 0.45, and 15.1 +/- 0.20 muM in 0, 6, 12, 18, and 24 mM malathion, respectively. The Comet assay showed a significant increase in DNA damage at the 24 mM malathion exposure. Taken together, our results indicate that malathion exposure at higher concentrations induces cytotoxic and genotoxic effects in HepG(2) cells, and its toxicity may be mediated through OS as evidenced by a significant production of MDA, an end product of lipid peroxidation.
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PMID:Malathion-induced oxidative stress, cytotoxicity, and genotoxicity in human liver carcinoma (HepG2) cells. 1939 48

Hypobaric hypoxia (HBH) can produce neuropsychological disorders such as insomnia, dizziness, memory deficiencies, headache and nausea. It is well known that exposure to HBH cause alterations of neurotransmitters and cognitive impairment in terms of learning and memory. But the mechanisms are poorly understood. The present study aimed to investigate the cholinergic system alterations associated with simulated HBH induced cognitive impairment. Male Sprague-Dawley rats were exposed to HBH equivalent to 6100 m for 7 days in a simulation chamber. The cognitive performance was assessed using Morris Water Maze (MWM) task. Cholinergic markers like acetylcholine (ACh) and acetylcholinesterase (AChE) were evaluated in hippocampus and cortex of rats. Neuronal damage was also studied through morphological changes. Exposure to HBH led to impairment in relearning ability and memory retrieval and it was accompanied by decrease in ACh level and increase in AChE and led to morphological damage. Administration of AChE inhibitor (AChEI), physostigmine (PHY) and galantamine (GAL) to rats during HBH exposure resulted in amelioration of the deleterious effects induced by HBH. The AChEIs were able to improve the cholinergic activity by restoring the level of ACh by blocking the AChE activity. In addition, the AChEIs also prevented neurodegeneration by reducing the AChE level in cortical and hippocampal neurons.
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PMID:Acetylcholinesterase inhibitors enhance cognitive functions in rats following hypobaric hypoxia. 1944 92

Acute gastrointestinal events (mostly manifested by nausea, vomiting, or loss of appetite) are class effects of all cholinesterase inhibitors, which are prescribed for the treatment of Alzheimer's disease. The underlying mechanism, however, has been unclear. Because corticotropin-releasing hormone is related to appetite control, we focused on the activation of the hypothalamo-pituitary-adrenal system and food intake following the administration of the cholinesterase inhibitor, donepezil, in rats. We monitored the plasma concentrations of adrenocorticotropic hormone, c-Fos, in the paraventricular nucleus, and intakes of rat chow for 3 h after the first administration of donepezil, and 2 weeks later, after daily administration of donepezil. The intragastric administration of 3 mg/kg of donepezil significantly increased the plasma adrenocorticotropic hormone levels and c-Fos expression in the paraventricular nucleus, and decreased the food intake on the first day. The increase in adrenocorticotropic hormone and loss of appetite after oral administration of the drug were attenuated after daily administration for 2 weeks.
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PMID:Responses of hypothalamo-pituitary-adrenal axis to a cholinesterase inhibitor. 1973 98

Galantamine (Reminyl) is a tertiary alkaloid, originally isolated from the Caucasian snowdrop and several Amaryllidaceae plants. It has been used for over 40 years in anesthetics to reverse the effects of curarization. In vitro and in vivo studies have confirmed that galantamine is an orally-active, reversible, competitive inhibitor of brain cholinesterase, which is 50 times more selective for acetylcholinesterase, compared with butyrylcholinesterase. Galantamine has also been shown to allosterically potentiate sub-maximal nicotinic responses to acetylcholine. This direct effect on pre- and postsynaptic nicotinic receptors may represent a second mechanism of action for enhancing cholinergic function, but as yet it is unclear as to whether that has any clinical significance. Galantamine has been licensed for use in the symptomatic treatment of Alzheimer's disease patients, after proving its efficacy in a number of well-designed clinical trials. It has to be administered twice daily and has shown good tolerability, which typically for drugs of this class, is improved by slow titration. The most common side effects are: nausea, vomiting, diarrhea and anorexia. Galantamine appears to be an effective treatment for Alzheimer's disease comparable with the other acetylcholinesterase inhibitors in improving cognition and function with growing evidence for its effects on behavior and caregiver burden.
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PMID:Galantamine: a new treatment for Alzheimer's disease. 1981 Oct 27

Oral cholinesterase inhibitors (ChEIs) are associated with side effects such as nausea and vomiting. The use of transdermal patches for ChEI delivery may help to minimize these problems. The objective of this review was to consider available data from patients switching from oral ChEIs to transdermal rivastigmine treatment, and to suggest practical guidelines for patients wishing to do this. Literature database and reference list searches were performed to identify suitable publications. Data from two clinical trials and a series of open observational studies, in which patients were switched to the rivastigmine patch from oral rivastigmine, donepezil tablets, or galantamine, were evaluated. Adverse events were tabulated. In the studies reported here, nausea was reported in up to 3.2% and vomiting in up to 1.9% of patients switching to the rivastigmine patch from oral rivastigmine. Similar rates (up to 3.8% of patients for nausea and 0.8% of patients for vomiting) were reported when switching to the rivastigmine patch from donepezil tablets, and no nausea or vomiting was reported in a case study of patients switching to the rivastigmine patch from galantamine tablets. Switching regimes used in clinical trials appeared well tolerated. Data support recommendations for patients on high rivastigmine capsule doses to switch directly to the 9.5 mg/24 h rivastigmine patch, while those on lower oral rivastigmine doses should start on the 4.6 mg/24 h patch for 4 weeks before increasing to the 9.5 mg/24 h patch. This latter regimen is recommended for patients on other oral cholinesterase inhibitors if switching is medically indicated or requested by the patient or the caregiver.
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PMID:Switching from oral cholinesterase inhibitors to the rivastigmine transdermal patch. 2007 Jul 89

Inhibition of acetylcholinesterase (AChE) and therefore prevention of acetylcholine degradation is one of the most accepted therapy opportunities for Alzheimer s disease (AD), today. Due to lack of selectivity of AChE inhibitor drugs on the market, AD-patients suffer from side effects like nausea or vomiting. In the present study the isolation of two alkaloids, infractopicrin (1) and 10-hydroxy-infractopicrin (2), from Cortinarius infractus Berk. (Cortinariaceae) is presented. Both compounds show AChE-inhibiting activity and possess a higher selectivity than galanthamine. Docking studies show that lacking pi-pi-interactions in butyrylcholinesterase (BChE) are responsible for selectivity. Studies on other AD pathology related targets show an inhibitory effect of both compounds on self-aggregation of Abeta-peptides but not on AChE induced Abeta-peptide aggregation. Low cytotoxicity as well as calculated pharmacokinetic data suggest that the natural products could be useful candidates for further drug development.
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PMID:Acetylcholinesterase inhibitors from the toadstool Cortinarius infractus. 2017 90


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