UMLS:C0027497 - FACTA Search

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)

Apomorphine is a dopamine agonist administered subcutaneously for the management of motor symptoms of Parkinson's disease (PD). Patients with Parkinsonian syndrome underwent an apomorphine challenge for therapeutic efficacy, a positive response being a reduction of > 15% score on motor unified PD rating scale. Of the 42 patients, aged 37-81, disease duration 12 months to 20 years, 36 had a positive response. Six non-responders were later diagnosed as non-PD as compared with only two of the 36 responders. Tremor-predominant patients obtained higher motor response. Few patients demonstrated a delayed positive response. Seven (three idiopathic PD (iPD), four non-PD) suffered adverse reactions of nausea, vomiting or ill-sustained symptomatic fall in BP. Majority of the patients who continued with apomorphine therapy were able to reduce levodopa and achieved an improvement in dyskinesia and motor symptoms. Thirteen responding patients were managed by increasing dopamine agonists. Five patients, intolerant of oral dopamine agonists, were able to beneficially tolerate apomorphine. Age and disease duration did not influence tolerability or efficacy. The patients treated with apomorphine were able to significantly reduce the dose of levodopa, and there was a reduction in dyskinesia, hallucinations and fluctuations (all p < 0.05). In some patients, apomorphine prevented admission to institutions. We also describe the use of apomorphine in acutely ill patients unable to ingest oral medication. Apomorphine seems to have a diagnostic element for iPD. Its use leads to a reduction in dyskinesia, improvement in motor symptoms and prevention of institutional care. Apomorphine test also identifies patients likely to benefit with an increase in oral medication. Age and disease duration should not prevent the use of this valuable drug. Apomorphine also has a role in acutely ill PD patients.
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PMID:Diagnostic and therapeutic value of apomorphine in Parkinsonian patients. 1560 66

This article is a review of the various treatments that are currently available, in particular in France, for the treatment of bipolar disorders. This article specifically addresses the use of novel antipsychotic agents as alternative therapy to a lithium therapy and/or the use of conventional antipsychotics. The prevalence of bipolar disorder over a lifetime is around 1% of the general population. Bipolar disorder consists of alternating depressive and manic episodes. It mainly affects younger subjects, and is often associated with alcohol and drug addictions. There are two main subtypes of bipolar disorder. According to the DSM IV-R, type 1 of bipolar disorder is characterised when at least one manic episode (or a mixed episode) has been diagnosed. Type 2 of bipolar disorder is related to patients enduring recurrent depressive episodes but no manic episode. Type 2 affects women more frequently as opposed to type 1 affecting individuals of both sexes. Manic-depressive disorder (or cyclo-thymic disorder) appears in relation to patients who has never suffered manic episode, mixed episode or severe depressive episode but have undergone numerous periods with some symptoms of depression and hypomanic symptoms over a two-year period during which any asymptomatic periods last no longer than two months. The average age of the person going through a first episode (often a depressive one) is 20 years-old. Untreated bipolar patients may endure more than ten manic or depressive episodes. Finally, in relation to 10 to 20% of patients, the bipolar disorder will turn into a fast cycle form, either spontaneously or as a result of certain medical treatments. Psychiatrists are now able to initiate various treating strategies which are most likely to be effective as a result of the identification of clinical subtypes of the bipolar disorder. Lithium therapy has been effectively and acutely used for patients with pure or elated mania and its prophylaxis. However, lithium medication may worsen depressive symptoms when used for a long term maintenance therapy. Additionally, mixed mania, rapid cycling type patients and bipolar disorder associated with substance abuse do not respond well to lithium therapy. In addition to the lithium therapy or in place of a lithium therapy, one can report the frequent use of antipsychotic agents in respect of patients with bipolar disorder during both the acute and maintenance phases of treatment. Antipsychotic agents have been used for almost forty years and may be used in combination with a lithium therapy. Conventional antipsychotics are effective but they may induce late dyskinesia, weight gain, sedation, sexual dysfunction and depression. These adverse side effects often lead to non compliance in particular in circumstances where antipsychotic agents are combined with a lithium therapy. A number of alternative somatic treatment approaches have been reported for patients who do not respond well or who are intolerant to lithium therapy. As such, valproate has received regulatory approval for the acute treatment of mania and carbamazepine has been indicated for this condition in a number of countries. Divalproex (Depakote) has recently obtained the authorization to market in France and may be prescribed for manic states or hypomanic states that do not tolerate lithium therapy or for which lithium therapy is contraindicated. A number of other anticonvulsants (lamotrigine, gabapentin and topiramate) are currently being tested. Because of the side effects of the conventional antipsychotic agents, atypical antipsychotic agents are currently on trial and appear to be of interest in the treatment of bipolar disorders. Currently, a number of prospective studies are available with clozapine, risperidone and olanzapine in the treatment of bipolar disorder. Most are short-term studies. Recent randomised, double-blind, placebo-controlled studies have shown clozapine, risperidone and olanzapine to be effective with antimanic and antidepressive effects, both as monotherapy and as add-on maintenance therapy with lithium or valproate. They also have a favorable side effect profile and a positive effect on overall functioning. Similarly, valproate combined with antipsychotics provides greater improvement in mania than antipsychotic medication alone and results in lower dosage of the antipsychotic medication. There is currently no double-blind study regarding the use of clozapine for bipolar disorders. However, based on the results of a number of open-label studies, clozapine appears to be effective in relation to schizo-affective and bipolar patients including those with rapid cycling or those who respond inadequately to mood stabilizers, carbamazepine, valproate or conventional antipsychotics. Clozapine seems to be more appropriate for bipolar and schizo-affective patients than schizophrenics. In particular, studies show that patients with manic and mixed-psychotic state of illness are better responders than patients with major depressive syndromes. Four open studies suggest the efficacy of clozapine in the maintenance treatment of bipolar disorder and three prospective, open-label studies show the efficacy of clozapine in the manic state of the illness. However, the number of patients in the studies was not important and these studies are not controlled. Clozapine has also adverse side affects, one of which consisting of a major risk of agranulocytosis and, potentially, death. In addition, clozapine has been shown to produce significant weight gain and sialorrhea as well as significant anticholinergic effects. As a result, clozapine should not be prescribed in the first place. As opposed to clozapine, there are open-label reports and controlled studies in respect of risperidone and olanzapine. Two recent double-blind studies of acute mania found olanzapine to be more effective than placebo. Based on these two studies, olanzapine has recently been approved for the indication of mania. The effects of olanzapine and divalproex in the treatment of mania have also been compared in a large randomized clinical trial. The olanzapine treatment group had significantly greater mean improvement of mania ratings and a significantly greater proportion of patients achieving protocol-defined remission. Significantly more weight gain and cases of dry mouth, increased appetite and somnolence were reported with olanzapine while more cases of nausea were reported with divalproex. The comparison of olanzapine with lithium for the treatment of mania has also been the subject of a double-blind randomized controlled trial. That study shows no differences between the two drugs. While these studies support the idea that olanzapine has direct acute anti-manic effects, a number of authors are of the opinion that olanzapine may have specific prophylactic mood-stabilizing properties. Olanzapine would appear to be effective in the maintenance treatment, as it exhibited both antimanic and antidepressant effects. Systematic trials have shown that risperidone may be effective and safe in the treatment of acute mania, as an add-on therapy with lithium or valproate (open studies and two controlled double-blind studies) and as monotherapy (open studies). In an open, multi-center, 6-month study, risperidone seems to be effective and safe as long-term adjunctive therapy in treatment-resistant bipolar and schizo-affective disorders, with no exacerbation of manic symptoms. Risperidone had few adverse side effects (and where there were any, they were mostly mild), mostly consisting of APS and weight gain. A naturalistic comparison of clozapine, risperidone and olanzapine in the treatment of bipolar disorder suggests that the efficacy and tolerability of the three treatments are similar. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. However, this may partially be caused by the use of mood-stabilizing agents. Bipolar and schizo-affective patients now require combination therapy approach because of the cyclic nature of these disorders. Many studies report the combination of mood-stabilizing agents with conventional antipsychotics and atypical antipsychotics. Combination therapies produce a number of adverse side effects. Atypical antipsychotics (other than clozapine) are now rated as first-line agents for adjunctive treatment of mania because they produce less adverse side effects. Atypical antipsychotics are also rated as first-line agents for combined treatment of psychotic depression and they are strongly preferred when an antipsychotic is required for long-term maintenance.
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PMID:[Antipsychotics in bipolar disorders]. 1562 46

Ropinirole (Requip, GlaxoSmithKline) is a novel nonergoline dopamine D2 agonist indicated for the treatment of early and advanced Parkinson's disease. It is mainly metabolized by the liver and its elimination half-life is approximately 5.8 h. When used as monotherapy in early Parkinson's disease, ropinirole improves signs and symptoms of the disorder. When used as an adjunct to levodopa in advanced Parkinson's disease patients with motor fluctuations, ropinirole reduces off time and allows a reduction of levodopa dose. The initial use of ropinirole in early Parkinson's disease to which levodopa is added when necessary, has been demonstrated to lead to a lower incidence of dyskinesias compared with treatment with levodopa alone. An 18F-dihydroxyphenylalanine positron emission tomography study suggested the possibility that ropinirole could slow the progression of loss of dopamine neurons compared with treatment with levodopa but this remains to be proven. Side effects of ropinirole include nausea, somnolence, edema, orthostatic hypotension, hallucinations and dyskinesia. A once-daily formulation of ropinirole is currently in development that has the potential for greater convenience, improved tolerability and greater efficacy.
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PMID:Ropinirole therapy for Parkinson's disease. 1585 77

Biliary dyskinesia is a potential cause for acalculous biliary colic in pediatric patients. A triad of symptoms and signs, consisting of abdominal pain (with or without associated nausea or fatty food intolerance), absence of gallstones, and an abnormally low cholecystokinin-stimulated gallbladder ejection fraction is used to diagnose the disorder. In several small pediatric case series, cholecystectomy resulted in symptomatic improvement in a majority of patients with biliary dyskinesia. However, the diagnosis of biliary dyskinesia and appropriate management remain controversial. This review discusses the purported pathophysiology of biliary dyskinesia and the data available regarding diagnosis and treatment of this entity in the pediatric population.
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PMID:Biliary dyskinesia in pediatrics. 1653 82

Apomorphine, a non-ergot derivative, is a potent, directly acting dopamine receptor agonist with high affinity to D4, lower to D2, D3, D5, the lowest to D1-like dopamine receptors as well as to serotonin and adrenoreceptors. Subcutaneous apomorphine is currently used in Parkinson's disease as an add-on to levodopa therapy or monotherapy for management of sudden, unexpected and refractory to levodopa-induced off state and fluctuation in advanced stage of illness. Many clinical trials have shown markedly (about 50-72%) reduced time of off phases. Other indications include the challenge test for determining the dopaminergic responsiveness. Apomorphine is used subcutaneously either as intermittent rescue injections or continuous infusions. Several other routes - transdermal, sublingual, intranasal, rectal and intravenous infusion - have been tried. Oral administration is not recommended. Apomorphine has rapid onset of antiparkinsonian action, qualitatively comparable to that of levodopa, short duration of action and stable efficacy with usually mild adverse events similar to other dopamine agonists. Domperidone or trimethobenzamide should be introduced before starting apomorphine treatment to reduce occurrence of peripheral adverse events (nausea, vomiting, orthostatic hypotension). Dyskinesias, sleep disturbances, hallucinations, delusion, oedema and yawning can occur, but some side effects are connected only with a specific route (for example skin nodules appearing during subcutaneous administration). Despite its long history, apomorphine is registered and used in only a few countries. Apomorphine warrants wider application in treatment of advanced Parkinson disease but the high cost of the drug, the necessity of concomitant treatment for prevention of side effects and subcutaneous administration restrict its use.
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PMID:[Apomorphine in off state--clinical experience]. 1794 58

Parkinson's disease (PD) is a progressive, neurodegenerative disorder which involves the loss of dopaminergic neurons of the substantia nigra pars compacta. Current therapy is essentially symptomatic, and L-Dopa (LD), the direct precursor of dopamine(DA), is the treatment of choice in more advanced stages of the disease. Substitution therapy with LD is, however, associated with a number of acute problems. The peripheral conversion of LD by amino acid decarboxylase (AADC) to DA is responsible for the typical gastrointestinal (nausea, emesis) and cardiovascular (arrhythmia, hypotension) side effects. To minimize the conversion to DA outside the central nervous system (CNS) LD is usually given in combination with peripheral inhibitors of AADC (carbidopa and benserazide). In spite of that, other central nervous side effects such as dyskinesia, on-off phenomenon and end-of-dose deterioration still remain. The main factors responsible for the poor bioavailability and the wide range of inter- and intra-patient variations of plasma levels are the drug's physical-chemical properties: low water and lipid solubility, resulting in unfavourable partition, and the high susceptibility to chemical and enzymatic degradation. In order to improve the bioavailability, the prodrug approach appeared to be the most promising and some LD prodrugs have been prepared in an effort to solve these problems. We report here a review of progress in antiparkinson prodrugs, focusing on chemical structures mainly related to LD, DA and dopaminergic agonists.
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PMID:Antiparkinson prodrugs. 1825 29

After 40 years of clinical experience, levodopa remains the gold standard treatment for Parkinson's disease (PD) despite the recent emergence of a host of new therapies. Some physicians are cautious when prescribing levodopa because of its association with motor complications. Evidence now suggests that levodopa-associated complications are a result of deep troughs in delivery of levodopa to the brain caused by the short plasma half-life of conventional levodopa formulations (levodopa and a dopa decarboxylase inhibitor [DDCI]). Dosing strategies, such as dose increases and dose fractionation, may be effective in the short term. For the longer-term, levodopa/carbidopa/entacapone provides pharmacokinetically optimized levodopa therapy that significantly increases the plasma half-life and bioavailability of levodopa, providing more consistent plasma levodopa levels without deep troughs. Evidence from clinical trials in PD patients experiencing re-emergence of symptoms due to wearing-off has consistently shown that levodopa/DDCI and entacapone significantly increases ON-time and affords greater functionality, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) with conventional levodopa. These trials have also shown that levodopa/DDCI and entacapone is generally well tolerated, with notable adverse events including worsening dyskinesia, nausea and diarrhea. Patients experiencing re-emergence of symptoms due to wearing-off may benefit from optimized levodopa therapy with levodopa/carbidopa/entacapone.
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PMID:Optimizing levodopa therapy for Parkinson's disease with levodopa/carbidopa/entacapone: implications from a clinical and patient perspective. 1872 16

We performed a 39-week, randomized, double-blind, multicenter study to compare the efficacy, safety, and tolerability of levodopa/carbidopa/entacapone (LCE, Stalevo) with levodopa/carbidopa (LC, Sinemet IR) in patients with early Parkinson's disease (PD). Four hundred twenty-three patients with early PD warranting levodopa were randomly assigned to treatment with LCE 100/25/200 or LC 100/25 three-times daily. The adjusted mean difference in total Unified Parkinson's disease Rating Scale (UPDRS) Parts II and III between groups using the analysis of covariance model (prespecified primary outcome measure) was 1.7 (standard error = 0.84) points favoring LCE (P = 0.045). Significantly greater improvement with LCE compared with LC was also observed in UPDRS Part II activities of daily living (ADL) scores (P = 0.025), Schwab and England ADL scores (blinded rater, P = 0.003; subject, P = 0.006) and subject-reported Clinical Global Impression (CGI) scores (P = 0.047). There was no significant difference in UPDRS Part III or investigator-rated CGI scores. Wearing-off was observed in 29 (13.9%) subjects in the LCE group and 43 (20.0%) in the LC group (P = 0.099). Dyskinesia was observed in 11 (5.3%) subjects in the LCE group and 16 (7.4%) in the LC group (P = 0.367). Nausea and diarrhea were reported more frequently in the LCE group. LCE provided greater symptomatic benefit than LC and did not increase motor complications.
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PMID:Double-blind trial of levodopa/carbidopa/entacapone versus levodopa/carbidopa in early Parkinson's disease. 1905 33

Experience with laparoscopic cholecystectomy for biliary dyskinesia in children remains limited. The aim of this study was to examine the results of a single institution's experience with laparoscopic cholecystectomy for the treatment biliary dyskinesia in the pediatric population. Medical records were reviewed on all patients younger than age 18 who underwent laparoscopic cholecystectomy at our institution from July 2004 to December 2006. Patients undergoing surgery for biliary dyskinesia, as evidenced by a preoperative gallbladder ejection fraction of 40 per cent or less, comprised the study group. Of the 51 pediatric laparoscopic cholecystectomies, 30 (58.8%) were performed for biliary dyskinesia. The patients' ages ranged from 7 to 17 (mean, 12.67 years; SD, 2.75). Symptoms consisted of chronic right upper quadrant pain (96.67%), nausea/vomiting (73.33%), back pain (30.0%), weight loss (13.33%), and a history of pancreatitis (6.66%). The amount of time between onset of symptoms and surgery was as follows: 1 to 3 months (34.62%), 4 to 6 months (30.77%), 7 to 12 months (7.69%), and greater than 1 year (26.92%). Gallbladder ejection fraction ranged from 1 to 36 per cent (mean, 14.7%). Seven of the 30 (26.67%) underwent endoscopic evaluation as part of their preoperative workup (six upper endoscopy, one colonoscopy), all of which were noncontributory. Pathology revealed chronic cholecystitis in 26 of 30 (93.3%), no abnormalities in three of 30 (10.0%), and unexpected cholelithiasis in one of 30 (3.33%). No perioperative complications were encountered. Twenty-nine of the 30 patients were available for follow up and all but one reported relief of symptoms (96.55%). This study supports the use of laparoscopic cholecystectomy as a safe and effective treatment for biliary dyskinesia in the pediatric population. The success rate in our study was substantially higher than that reported in previous series. Routine preoperative endoscopy was not used and was reserved for investigation of ambiguous or unrelated complaints.
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PMID:Laparoscopic cholecystectomy for treatment of biliary dyskinesia is safe and effective in the pediatric population. 2114 Jul 5

Ropinirole prolonged release is a once-daily, 24-hour formulation of ropinirole, a non-ergot dopamine agonist. It is approved as monotherapy and as an adjunct to levodopa in the treatment of Parkinson's disease (PD). Several potential advantages of ropinirole prolonged release compared to the immediate release formulation include maintaining more consistent dopaminergic activity with steadier plasma levels, increased tolerability, greater compliance from a simpler once-daily dosing regimen and ease in dose titration. In a randomized, double-blind, non-inferiority, crossover study, ropinirole prolonged release was shown to have comparable efficacy and tolerability to immediate release ropinirole in early PD patients, with significantly greater compliance. Subjects were converted overnight between ropinirole formulations without loss of efficacy and with good tolerability. In a randomized, double-blind, placebo-controlled study in advanced PD, daily "off" time was reduced by an average of 2.1 hours with ropinirole prolonged release compared to 0.4 hours with placebo. Patients on ropinirole prolonged release were also more likely to require less daily levodopa. Ropinirole prolonged release is well tolerated with a similar adverse effect profile to other non-ergot dopamine agonists. The most common adverse effects include dyskinesia, nausea, dizziness, hallucinations, somnolence, abdominal pain or discomfort and orthostatic hypotension. Ropinirole prolonged release is a safe and effective treatment option for both early and advanced PD. This manuscript briefly reviews the current pharmacological treatment options for PD and provides a more detailed review of the currently available data regarding ropinirole prolonged release as a treatment option for PD.
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PMID:A review of ropinirole prolonged release in Parkinson's disease. 1950 79

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