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)

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

(1) The reference symptomatic treatment for mild to moderate Alzheimer's disease is a cholinesterase inhibitor such as donepezil, but efficacy is only moderate and only about 10% of those patients treated actually benefit. (2) Galantamine is the fourth cholinesterase inhibitor to be marketed in France for Alzheimer's disease. The clinical file contains data from five double-blind placebo-controlled trials lasting 3-6 months, but no data comparing galantamine with other drugs. (3) These trials show that about 5-13% of patients treated with galantamine may be improved. (4) Adverse effects are very frequent, and are similar to those of other cholinesterase inhibitors, i.e. nausea, vomiting, diarrhoea, abdominal pain, dyspepsia, etc. (5) For patients who are eligible for drug therapy, the reference treatment is still donepezil, for want of anything better.
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PMID:Galantamine: new preparation. The fourth cholinesterase inhibitor for Alzheimer's disease. 1182 42

The objective of this study was to compare the pharmacokinetics and safety of galantamine in subjects with hepatic impairment with those in healthy subjects. This was an open-label study in which a single oral 4-mg dose of galantamine was administered to volunteers with mild (Child-Pugh score of 5-6, n = 8), moderate (Child-Pugh score of 7-9, n = 8), or severe hepatic impairment (Child-Pugh score of 10-15, n = 1) and to healthy, matched control subjects (n = 8). Galantamine pharmacokinetics and safety (adverse events, laboratory test results, electrocardiograms, vital signs, and cardiac events) were assessed over 6 days after administration of galantamine. The pharmacokinetic parameters of galantamine were similar in subjects with mild hepatic impairment compared with healthy controls. Compared with the healthy control group, subjects with moderate hepatic impairment showed relative increases in the area under the plasma-concentration curve from zero to infinity (AUC0-infinity) (+33%) and terminal half-life (t1/2) (+30%) (p = 0.051 and p = 0.003, respectively), a 23% relative decrease in total plasma clearance (p = 0.061), and a small but significant relative increase in the fraction of free plasma galantamine (p = 0.009). Galantamine was well tolerated by all subjects. There were no serious adverse events (AEs) or premature withdrawals from the study because of AEs. Reported AEs were headache (three cases), nausea (one case), and paresthesia (one case). There were no clinically relevant changes in clinical laboratory findings, vital signs, and electrocardiograms. Low patient recruitment (n = 1) precluded statistical analysis of galantamine pharmacokinetics and safety in severe hepatic impairment. It was concluded that the pharmacokinetics of galantamine in subjects with mild hepatic impairment was similarto those in healthy subjects. In subjects with moderate hepatic impairment, galantamine clearance was decreased by approximately 23% compared with normal volunteers. Galantamine was also well tolerated and appeared to be safe in subjects with mild ormoderate hepatic impairment. Based on the study results, it appears that it would not be necessary to adjust doses of galantamine during administration to subjects with mild hepatic impairment. In subjects with moderately impaired hepatic function, dose titration should proceed cautiously. Unfortunately, difficulties with patient recruitment did not allow adequate assessment of the safety of galantamine in subjects with severe hepatic impairment in this study. Therefore, the use of galantamine in subjects with severe hepatic impairment is not recommended.
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PMID:Pharmacokinetics and safety of galantamine in subjects with hepatic impairment and healthy volunteers. 1193 68

The pharmacology, dosage, adverse effects, efficacy, and economics of galantamine hydrobromide are discussed. Galantamine hydrobromide is a tertiary alkaloid that has been extracted from plant sources and is now synthesized for use in the treatment of mild to moderate Alzheimer's disease (AD). Galantamine acts both as a reversible competitive inhibitor of acetylcholinesterase (AChE) and as an allosteric modulator of nicotinic acetylcholine receptors. The recommended starting dosage is 4 mg (as the hydrobromide) twice daily. The dosage should be increased in increments of 8 mg/day in two divided doses after four weeks at a given dosage until a maintenance dosage of 16-24 mg/day in two divided doses is reached. Adverse effects are primarily mild and cholinergic and include nausea, vomiting, diarrhea, and dizziness. Five large clinical trials demonstrated that galantamine is more effective than placebo in controlling the symptoms of mild to moderate AD. Optimal therapy appears to require early initiation of the drug and a dosage-adjustment period of eight weeks. In one study, galantamine delayed full-time care by 10% and reduced the overall cost of care by $528. Because galantamine has not yet been compared directly with other AChE inhibitors, cost should be the principal factor weighed during formulary evaluations. Galantamine provides the clinician with another choice of an AChE inhibitor for use in treating AD.
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PMID:Galantamine hydrobromide: an agent for Alzheimer's disease. 1263 50

The objective of this study was to assess the effectiveness and tolerability of galantamine in patients with mild-to-moderate Alzheimer's disease (AD) in everyday clinical practice. Patient selection was made on 36 sequential patients attending Belfast City Hospital Memory Clinic between December 2000 and June 2001. Patients were treated with galantamine for 6 months, starting from 4 mg twice daily increasing to 8 mg twice daily and then to 12 mg twice daily at 4-weekly intervals. Patients (25 females, 11 males), mean age 78 years (59-90), were diagnosed with probable AD and had a mini-mental state examination (MMSE) score of 10-26. Efficacy was assessed using the MMSE, neuropsychiatric inventory (NPI), neuropsychiatric inventory caregiver distress (NPI-D) scale and the Bristol activities of daily living (B-ADL) scale at baseline and after 3 and 6 months of treatment. Mean improvements were noted on all four measures of efficacy at 3 and 6 months; improvements were significant on the MMSE, NPI and NPI-D at 3 months and on the NPI-D at 6 months. Galantamine was overall well tolerated. The most common adverse events were gastrointestinal, particularly nausea. Four patients stopped treatment due to adverse events, and seven were stabilised on 8 mg twice daily as they were unable to tolerate the target dose. This naturalistic study confirms clinical trial data, which shows galantamine improves cognition and behavioural symptoms and is overall well tolerated.
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PMID:A 6-month open-label study of the effectiveness and tolerability of galantamine in patients with Alzheimer's disease. 1505 62

The objective is to evaluate the efficacy of galantamine when a slow titration regimen is employed in Thai Alzheimer's disease (AD) patients with or without cerebrovascular disease and vascular dementia (VaD). A 6-month, multicentre, open-label, uncontrolled trial was undertaken in 75 AD patients. Eligible patients received an initial galantamine dose of 8 mg/day and escalated over 5-8 weeks to maintenance doses of 16 or 24 mg/day. Primary efficacy measures were AD Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician's Interview-Based Impression of Change-Plus version (CIBIC-plus). The Behavioural Pathology in AD Rating Scale (BEHAVE AD), the AD Cooperative Study Activities of Daily Living Inventory and Pittsburgh Sleep Quality Index were the secondary efficacy variables. Analyses were based on the intent-to-treat population. Treatment with galantamine showed significant improvement in cognition on the ADAS-cog and CIBIC-plus at month 6. Galantamine showed favourable effects on activities of daily living. Behavioural symptoms and sleep quality were also significantly improved (p < 0.05). Galantamine was well tolerated. The adverse events were mild-to-moderate intensity. The most frequent adverse events commonly reported were nausea (16.4%), dizziness (9.6%) and vomiting (6.8%). The results of this study may be consistent with galantamine being an effective and safe treatment for mild-to-moderate AD patients with or without cerebrovascular disease and VaD. Flexible dose escalation of galantamine was well tolerated. The daily maintenance dose of galantamine was 16 mg/day, followed by a back up dose of 24 mg/day.
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PMID:Efficacy study of galantamine in possible Alzheimer's disease with or without cerebrovascular disease and vascular dementia in Thai patients: a slow-titration regimen. 1670 Aug 49

Alzheimer's disease combined with cerebrovascular disease (AD with CVD) is associated with progressive decline, with CVD impacting AD onset and severity of progression. Subjects with confirmed diagnosis of AD with CVD were treated with galantamine during a six-month, randomized, placebo-controlled trial (N = 285). Responder analyses were performed for cognitive, behavioural and functional outcome measures. Galantamine treatment resulted in significantly greater cognitive and functional improvements compared with placebo at six months, and a significantly higher percentage of treatment responders. The proportion of responders demonstrating improved or maintained cognition on the 11-item AD assessment scale-cognitive subscale (ADAS-cog/11) was 60.5% for galantamine versus 46.0% for placebo (P = 0.013). The proportion of patients responding by at least four-points on the ADAS-cog/11 was significantly greater for the galantamine group compared with placebo (33.6% versus 17.2%; P = 0.003). Seventy-five percent of galantamine-treated subjects improved or remained stable as assessed by CIBIC-plus compared with 53.6% on placebo (P = 0.0006). Significantly higher responder rates were observed with galantamine for behaviour (64.9% versus 56.6%; P = 0.024), and numerically favourable responder rates were seen with galantamine for activities of daily living. Treatment-emergent adverse events were generally related with the gastrointestinal system (nausea 20% versus 10%; vomiting 12% versus 5%; galantamine and placebo groups, respectively). Three deaths occurred during double-blind treatment: 2 of 188 subjects receiving galantamine, and 1 of 97 subjects receiving placebo. These findings are consistent with a broad range of cognitive, functional and behavioural benefits with galantamine across the spectrum of AD and AD with CVD.
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PMID:Galantamine treatment in Alzheimer's disease with cerebrovascular disease: responder analyses from a randomized, controlled trial (GAL-INT-6). 1830 81

Forty-one Parkinson's disease patients with dementia (21 galantamine group, 20--control group) with onset of dementia at least two years after the manifestation of parkinsonian symptoms participated in this open-label controlled trial of galantamine in maximum dose 16 mg/day. Cognitive, psychiatric and motor symptoms were assessed before and after 4, 12 and 24 weeks of treatment using clinical assessment as well as rating scales, including the Mini-Mental State Examination (MMSE), ADAS-cog, clock drawing test, Frontal Assessment Battery (FAB), and the Neuropsychiatric Inventory (NPI-12) with assessment of caregiver distress. Patients treated with galantamine had better scores on MMSE (p<0,05), ADAS-cog (p<0,05), clock drawing test (p<0,05) and FAB (p<0,01) to the end of the trial comparing to the control group. NPI scores on individual items changed from baseline at week 12 and 24, showing benefits of galantamine treatment as compared to the controls, with significant difference for hallucinations (p=0,0002), anxiety (p=0,04), sleep disorders (p=0,04) and apathy (p=0,006). Galantamine therapy was associated with a significant reduction in caregiver distress (p=0,007), improvement of daily life activity (p=0,003). Gait, freezing and falls were improved in the galantamine group but a mild worsening of tremor was noted in two patients. Adverse events (drooling, postural hypotension, nausea, dysuria) were observed in 7 (30%) of galantamine treated patients.
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PMID:[Efficacy and safety of galantamine (reminyl) in the treatment of dementia in patients with Parkinson's disease (open-label controlled trial)]. 1842 56

An open controlled trial of the use of galantamine at a maximum dose of 16 mg/day included 41 patients with Parkinson's disease with dementia randomized to a galantamine treatment group (21 patients) and a control group (20 patients). Cognitive, neuropsychiatric, and motor symptoms were assessed clinically before the trial and at 4, 12, and 24 weeks, using the Mini Mental State Examination (MMSE), the cognitive Alzheimer's Disease Assessment Scale (ADAS-cog), the clock drawing test, the Frontal Assessment Battery (FAB), and the Neuropsychiatric Inventory (NPI) with assessment of distress in relatives. Patients treated with galantamine had better scores on the MMSE (p < 0.05),ADAS-cog (p < 0.05), the clock drawing test (p < 0.05), and the FAB (p < 0.01) at the end of the study period as compared with the control group. Changes in total point scores on the NPI-12 at the ends of weeks 12 and 24, as compared with the beginning of the trial, were in favor of the group treated with galantamine, with significant changes in the hallucinations (p = 0.0002), anxiety (p = 0.04), sleep disturbance (p = 0.04), and apathy (p = 0.006) sections. Galantamine treatment was accompanied by decreases in the level of distress in patients' relatives (p = 0.007) and improvements in daily activity (p = 0.003). Improvements in gait and decreases in freezing and falls were seen in the galantamine treatment group. However, two patients of this group showed minor increases in tremor. Side effects (drooling, postural hypotension, nausea, dysuria) occurred in seven patients (30%).
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PMID:Efficacy and safety of galantamine (reminyl) for dementia in patients with Parkinson's disease (an open controlled trial). 1897 3

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


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