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)

Vascular dementia (VaD), caused by stroke or small vessel disease, is the second most common form of dementia after Alzheimer's disease (AD). Donepezil, an acetylcholinesterase inhibitor currently indicated for use in patients with mild to moderate AD, has recently been evaluated in VaD. Donepezil 5 or 10mg once daily provided significant improvements in cognition, as determined by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), relative to placebo, after 24 weeks in patients with VaD. Pooled data from two, randomised, double-blind, phase III trials showed that the least-squares mean change from baseline score effect size for the ADAS-cog was -1.79 for donepezil 5mg once daily (p < 0.001) and -2.28 for donepezil 10mg once daily (p < 0.001) at 24 weeks (observed cases). Significant improvement in global functioning occurred with donepezil 5mg once daily compared with placebo (p = 0.003), but not with donepezil 10mg once daily, as measured by the Clinician's Interview-Based Impression of Change-plus version score (pooled data, observed cases). Donepezil was generally well tolerated in patients with VaD. Most adverse events were mild to moderate in nature, with diarrhoea and nausea being the most common.
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PMID:Donepezil: in vascular dementia. 1465 35

Observations on the neurochemistry of dementia with Lewy bodies (DLB) have suggested that cholinesterase inhibitors (ChEIs) might be beneficial in treating some clinical symptoms of DLB. A 24-week, multicenter open-label study was designed to assess the safety and efficacy of the ChEI galantamine in patients with DLB, and an interim analysis of results was performed at 12 weeks. Efficacy analyses were performed on data from 25 patients. Scores on the Neuropsychiatric Inventory (NPI-12) improved (decreased) by 7.52 points over the 12 weeks (marginally significant, p = 0.061). NPI-12 scores decreased by half in 12 of the 25 patients. Highly significant improvement was observed in scores on the NPI-4 subscale (delusions, hallucinations, apathy, and depression: p = 0.003). Scores on the Clinician's Global Impression of Change (CGIC) improved by 0.95 points (significant, p = 0.02). Improvements also were found in secondary efficacy variables, including cognitive, functional, activities of daily living, sleep and confusion assessments. Motor scores, as measured by the UPDRS motor subscale, showed mild improvement, which demonstrates that galantamine has no adverse effect on parkinsonian symptoms. Adverse events generally were transient and of mild-to-moderate intensity. Two of the 25 patients discontinued galantamine because of nausea and anorexia. One serious adverse event was recorded, but it was judged to be unrelated to the study medication.
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PMID:Efficacy and safety of galantamine in patients with dementia with Lewy bodies: a 12-week interim analysis. 1467 68

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

Reminyl (galantamine)-- a cholinesterase inhibiting component--was used in treatment of 15 patients with dementia featured by the presence of Levi bodies in brain neurons. The treatment duration was 16 weeks with elevation of the drug dosage every 4 weeks--from 8mg to 12 mg twice a day. Treatment evaluation was conducted clinically and by psychometrical tests and scales. Reminyl improved patient's state reducing cognitive, behavioral and psychotic disturbances. The highest effect was achieved in 2/3 patients. Side-effects (nausea, dizziness, dyspepsia, general sickness, etc) were observed in 47% cases. Only in 2 patients they caused treatment withdrawal. The absence of aggravation of extrapyramidal disorders is emphasized.
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PMID:[Reminyl efficacy in dementia with Levi bodies]. 1628 74

Methyl parathion - MP (C[8]H[10rsqbNO[5rsqbPS) is a restricted-use pesticide that has been widely used as an agricultural insecticide. It belongs to the class of organophosphate chemicals characterized by their ability to inhibit acetylcholinesterase activity. The main route of human exposure is inhalation, but dermal contact and inadvertent ingestion can also be substantial. Populations that are susceptible to MP exposure primarily are applicators, manufacturers and individuals living near application and/or disposal sites. Exposure has also been reported as a result of illegal indoor application. MP related health effects include headaches, nausea, night-waking, diarrhea, difficulty breathing, excessive sweating and salivation, incoordination, and mental confusion. Other symptoms including behavior problems, motor skill problems and impairment of memory recall have also been reported. The primary targets of toxicity are the hematopoietic system (serum cholinesterase inhibition), the cardiovascular system (cardiovascular lesions, abnormalities in heart rate and increase in heart-to-body ratio), the reproductive system (placental morphology, fibrosis and hemorrhage, and inhibition of DNA synthesis in seminiferous tubules), and the nervous system (headache, muscle weakness, insomnia, dizziness, and impaired memory). MP is believed to not have any carcinogenic effects. In an attempt to update its toxicologic profile, we hereby provide a critical review of MP-related environmental and toxicologic effects, with a special emphasis on their potential implications for public health.
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PMID:Environmental toxicology and health effects associated with methyl parathion exposure--a scientific review. 1681 98

Non-ulcer dyspepsia is a common clinical disorder characterised by reduced gastric motility. Safety concerns have restricted use of currently available prokinetic drugs. Itopride is a new safer prokinetic drug with dopamine D2 antagonism and acetylcholinesterase inhibitory actions. The ENGIP-II study was conducted to investigate the efficacy, and safety of itopride in patients of non-ulcer dyspepsia. There were significant reductions in upper abdominal pain, heartburn frequency, gastro-oesophageal regurgitation, nausea, bloating, early satiety after meals at day 3 only; whereas significant improvements were noted in belching, anorexia at day 6 and in vomiting at day 9. Thus, ENGIP-II study shows that itopride was well tolerated patients and appears to be the drug of choice in patients with non-ulcer dyspepsia.
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PMID:Evaluation of new gastro-intestinal prokinetic (ENGIP-II) study. 1682 70

Donepezil is a reversible inhibitor of acetylcholinesterase. Its commonest adverse events are nausea, diarrhoea, malaise, dizziness, and insomnia. Symptomatic cardiac rhythm disturbances associated with the use of donepezil are extremely unusual. An 82 year old patient with Alzheimer's disease (AD) developed complete atrioventricular block and ventricular tachyarrhythmia 1 month after starting treatment with donepezil, and was admitted to the emergency department because of dizziness and syncope. Immediately after admission, a temporary ventricular pacing catheter was placed in the right ventricle. Rhythm was observed to return to a normal sinus rhythm on the fourth day after implantation. Treatment of AD with cholinesterase inhibitors carries a risk of cardiac disturbances. In addition to sinusal bradycardia, it may lead to such major dysrhythmias as complete atrioventricular block and ventricular tachyarrhythmia, as in our case. In this report, we describe symptomatic complete atrioventricular block and ventricular tachyarrhythmia associated with the use of donepezil.
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PMID:Complete atrioventricular block and ventricular tachyarrhythmia associated with donepezil. 1685 1

Inhibition of acetylcholinesterase improves symptoms of dementia in patients with Parkinson's disease (PD). Dementia in PD has a cumulative incidence of up to 80% and is mainly caused by a distinct cholinergic deficit. Objectives of this investigator initiated multicenter open label trial were to confirm the efficacy of donepezil in the treatment of dementia in PD patients and to investigate the tolerability and safety of donepezil. The Mini Mental State Examination (MMSE)-score significantly increased in patients, who finished the trial. A detailed analysis of the various items of the MMSE revealed, that only task performance of orientation and recall significantly improved. Scores of the short syndrome test and the Clinical Global Impression Scale improved, motor impairment did not increase. Only 14 out of 24 PD patients finished the trial due to predominant onset of vomiting, nausea, dizziness and confusion. This may result from the titration regime of donepezil, that allows only 5 and 10 mg dosages. Participants with premature study termination had a significant longer duration of PD, less motivation and sleep disturbances at night. Treatment with donepezil was only effective in PD patients with dementia, who experience nearly no side effects from the drug.
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PMID:The DONPAD-study--treatment of dementia in patients with Parkinson's disease with donepezil. 1744 12

Nausea and/or vomiting are frequent dose-limiting class effects of cholinesterase inhibitors, occurring mostly during the dose-escalation phase. These untoward effects make it difficult to increase rivastigmine dosage above 6 mg daily in most patients. The antiemetic domperidone was given to 22 patients with Alzheimer's disease (9 men, 13 women; mean age 74.5+/-4.6 years; mean age at diagnosis: 73.1+/-5.0 years) in 15-day prophylactic cycles, starting 15 days before each dose escalation of rivastigmine above 6 mg daily. Only four patients (18.2%) experienced nausea, which was so mild that all patients reached >or=9 mg rivastigmine daily and 16 (72.7%) reached and maintained the top dosage (12 mg daily). An improvement or stabilization of Mini Mental State Examination scores was achieved in 54.5% of the patients. The treatment regimen was well tolerated; no patients stopped treatment because of adverse events. Further investigations assessing the role of domperidone in the prevention of rivastigmine-related gastrointestinal disturbances are warranted.
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PMID:Domperidone is effective in the prevention of rivastigmine-related gastrointestinal disturbances. 1763 13

Dry mouth produces a deterioration in oral health and impairs quality of life. There is a need for a novel approach to the pharmacological treatment of dry mouth. With a view to enhancing the cholinergic drive on minor salivary glands, whilst at the same time minimising adverse systemic effects, the cholinesterase inhibitor physostigmine was therefore sprayed, in a fixed volume, onto the oral mucosa of seven healthy subjects. Three concentrations (0.5%, 1% and 2%) were tested. The mean salivary output over time (0-105 min) was higher than that of placebo (p<0.05), as the area under the curve increased by 61%, 91% and 66% at physostigmine 0.5%, 1% and 2%, respectively. Two subjects experienced nausea at the highest physostigmine concentration, thus reflecting systemic effects. Heart rate, blood pressure and respiration were unaffected by the physostigmine treatment.
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PMID:Intraoral stimulation of salivary secretion with the cholinesterase inhibitor physostigmine as a mouth spray: a pilot study in healthy volunteers. 1765 55


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