Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of donepezil are reviewed. Donepezil is a synthetic noncovalent reversible inhibitor of acetylcholinesterase (AChE) for the treatment of mild to moderate dementia associated with Alzheimer's disease. In contrast to tacrine hydrochloride, the only comparable agent currently approved by FDA, donepezil exhibits a relatively high degree of selectivity for neuronal AChE as opposed to butyrylcholinesterase. It has a half-life of 60 hours in young adults and 104 hours in elderly patients. In clinical trials, donepezil has been associated with significant improvements in Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Interview-Based Impression of Change scores. The most common adverse effects associated with donepezil are nausea, diarrhea, anorexia, and vomiting, which are most likely to occur during dose initiation or adjustment. Hepatotoxicity, a dose-limiting adverse effect that sometimes requires discontinuation of tacrine, has not been reported with donepezil. Donepezil does not appear to interact with theophylline, cimetidine, warfarin, or digoxin. Ketoconazole and quinidine inhibit the metabolism of donepezil in vitro, but there is a lack of clinical data showing that these drugs decrease the clearance of donepezil. The initial recommended dosage is 5 mg daily before bedtime, with a dosage increase to 10 mg after four to six weeks according to the patient's response and tolerance. Donepezil appears to be preferable to tacrine as the initial agent for patients with mild to moderate dementia associated with Alzheimer's disease.
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PMID:Donepezil: an anticholinesterase inhibitor for Alzheimer's disease. 942 50

Cholinesterase inhibitors are currently the most established treatment strategy in Alzheimer's disease. The treatment effect appears mainly to be symptomatic. Effects on progression of the disease following long term treatment, and possible neuroprotective effects, have been investigated. Delay until nursing home placement has been reported. Three cholinesterase inhibitors, tacrine, donepezil and rivastigmine, are in clinical use. Other cholinesterase inhibitors, such as galantamine (galanthamine), metrifonate, physostigmine, eptastigmine, are currently under clinical evaluation. So far the efficacy appears to be comparable between the various cholinesterase inhibitors; treatment for up to 6 months has produced an improvement in Alzheimer's Disease Assessment Scale -- Cognitive Subscale score (ADAS-cog) of between 1.8 and 4.9 in patients with Alzheimer's disease. Tacrine, donepezil, galantamine and physostigmine are reversible inhibitors of acetylcholinesterase and butyrylcholinesterase, while metrifonate is considered to be an irreversible inhibitor and rivastigmine a pseudoirreversible inhibitor. Tacrine and physostigmine have lower bioavailability, 17 to 37% and 3 to 8%, respectively, than the other cholinesterase inhibitors such as rivastigmine, galantamine and donepezil (40 to 100%). The elimination half-life is considerably longer for donepezil (70 to 80h) in comparison to most of the other cholinesterase inhibitors (0.3 to 12h). Donepezil is therefore administered once daily in comparison to rivastigmine which is administered twice daily and tacrine which is administered 4 times daily. Simultaneous food intake lowers the plasma concentration of tacrine and reduces the adverse effects of rivastigmine. Drugs like theophylline and cimetidine have been reported to change the pharmacokinetics of tacrine and donepezil. In contrast, concomitant medication with various drugs with rivastigmine does not seem to cause any drug interactions in patients with Alzheimer's disease. Tacrine, donepezil and galantamine are metabolised via the cytochrome P450 (CYP) liver enzymes. Active metabolites are known for tacrine and galantamine. Rivastigmine is not metabolised via CYP enzymes, but via esterases and is excreted in the urine. Tacrine is associated with hepatotoxicity while other cholinesterase inhibitors seem devoid this adverse effect. Increased liver enzyme values have been observed in 49% of patients with Alzheimer's disease treated with tacrine. Rechallenge with tacrine reduces the incidence of elevated liver enzyme levels. Peripheral cholinergic adverse effects are common for the cholinesterase inhibitors, with an incidence ranging between 7 to 30%. For some cholinesterase inhibitors, such as rivastigmine, the cholinergic adverse effects such as nausea, vomiting, dizziness, diarrhoea and abdominal pain can be reduced by slowing the rate of dose titration.
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PMID:Cholinesterase inhibitors in the treatment of Alzheimer's disease: a comparison of tolerability and pharmacology. 988 90

The objective of this study was to evaluate the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of five fixed doses of ganstigmine (CHF 2819) in patients with probable Alzheimer's disease (AD). This randomized, double-blind, placebo-controlled trial evaluated five dose levels (5, 7.5, 10, 12.5, and 15 mg) administered orally once daily for 7 days. Adverse events and continuous telemetry were collected on successive panels of six patients (five active, one placebo). Acetylcholinesterase, butyrylcholinesterase, and plasma drug levels were measured. A total of 29 patients were randomized and 18 completed the study. A total of seven patients, including five of five in the 12.5-mg panel, discontinued because of adverse events. Four patients were withdrawn administratively from the first panel while an episode of atrial fibrillation (the only serious adverse event) was investigated. This panel was then repeated. Mild, transient headache or nausea were the most commonly reported adverse events. Multiple moderate adverse events in the 12.5-mg panel (including nausea, vomiting, and anorexia) led to the decision not to proceed with a 15-mg panel. Ten milligrams was determined to be the maximum tolerated dose. Ganstigmine exhibited nonlinear pharmacokinetics, was absorbed rapidly, and reached peak concentrations within 1 hour. Acetylcholinesterase inhibition was dose dependent and lasted as long as 24 hours. Ganstigmine, a novel cholinesterase inhibitor, was well tolerated within a dosing range of 5 to 10 mg. Once-daily dosing is supported by data on acetylcholinesterase inhibition.
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PMID:First clinical evaluation of ganstigmine in patients with probable Alzheimer's disease. 1278 20

We aimed to determine whether the cholinesterase inhibitor rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), would improve quality of life and cognitive function in 16 clinically stable subjects affected by schizophrenia in the residual phase. Study subjects began rivastigmine treatment at a dose of 1.5 mg bid. This dose was escalated at monthly intervals in increments of 1.5 mg bid to a maximum of 6 mg bid. All subjects were followed for 12 months. Quality of life was assessed using the Satisfaction with Life Domains Scale (SLDS, a self-report scale containing 10 "satisfaction" items); cognitive function, attentional function, and aspects of learning and memory were evaluated using common neuropsychological tests. Psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS). Rivastigmine treatment resulted in significant improvements in quality of life, which were paralleled by significant improvements in cognitive function, learning and memory, and trends for improvement in attention. The BPRS factor "anergia" showed significant improvement, while low baseline scores in other psychotic factors did not permit further improvements. There were no reports of nausea or vomiting. In conclusion, rivastigmine significantly improved quality of life in subjects with schizophrenia. These benefits may relate to the drug's effects on cognitive deficits and negative symptoms associated with the condition.
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PMID:Effects of rivastigmine on cognitive function and quality of life in patients with schizophrenia. 1464 12

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

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

An 86-year-old woman intentionally drank approximately 300 mL of a glyphosate-surfactant. She was found with consciousness disturbance and experienced several vomiting episodes. On arrival, serum biochemistry revealed a decreased level of butyrylcholinesterase (B-CHE) [11 (normal range: 180-450) IU/L]. Later, her B-CHE level further decreased to single-digit values, and she became comatose with involuntary movement and an increase in muscle tone. Her consciousness level and muscle tone improved with the recovery of her B-CHE level. Physicians should be alert for the occurrence of intermediate syndrome when the B-CHE levels of patients who have consumed a massive amount of glyphosate-surfactant show a prolonged decrease.
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PMID:Decrease in Butyrylcholinesterase Accompanied by Intermediate-like Syndrome after Massive Ingestion of a Glyphosate-surfactant. 3124 40