Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Newly introduced dopamine agonists, such as ropinirole, may offer advantages compared to such older drugs as bromocriptine in patients with advanced Parkinson's disease (PD) with response oscillations or waning efficacy. Dose equivalence of these two drugs, however, has not been well established, which may complicate switching in clinical practice. In 23 such patients with advanced PD no longer satisfactorily responsive to prolonged bromocriptine therapy (mean dose: 18.9 +/- 6.5 mg/d), we prospectively switched the medication to ropinirole administered at three different dose-ratios (5:1, 3:1, and 2:1), increased at monthly intervals. Selegiline remained unmodified in all 17 patients receiving this medication. A dose-ratio of bromocriptine to ropinirole of close to 2:1 (1.87; mean ropinirole dose: 10.1 +/- 2.5 mg/d) was the only dose that significantly reduced mean motor Unified Parkinson's Disease Rating Scale (UPDRS) scores ( p = 0.030, analysis of variance). Individually considered, however, four patients (21%) scored worse even at this dose-ratio when compared to baseline assessment on bromocriptine. "Off" time was reduced by 57.3% in fluctuating patients, and the dyskinesia score decreased by 53.8%, although the changes were not statistically significant. Higher bromocriptine to ropinirole dose ratios (i.e., 5:1 and 3:1) resulted in "off"-time increases in half of the patients with fluctuations, and two previously stable patients developed a wearing-off effect and one other patient experienced off-time dystonia. One patient developed dose-dependent dopaminomimetic psychotic symptoms with ropinirole. In conclusion, "off"-time motor scores and possibly "off"-time duration, and severity of dyskinesias in patients with advanced PD with prolonged bromocriptine therapy may improve in a majority of cases by switching to ropinirole, provided that the latter drug is administered at a dose ratio of 2:1 compared to bromocriptine. Higher dose ratios are often ineffective or may even cause a clinical worsening of symptoms in some patients.
 ...
PMID:Switching from bromocriptine to ropinirole in patients with advanced Parkinson's disease: open label pilot responses to three different dose-ratios. 1180 10

The novel atypical antipsychotic ziprasidone has a pharmacologic profile notable for potent agonism of serotonin (5-HT)1A receptors, antagonism at 5-HT1D receptors, and reuptake inhibition of norepinephrine. 5-HT1A receptor agonism, in particular, suggests anxiolytic activity, and ziprasidone has shown preliminary efficacy in treating the symptoms of anxiety associated with psychotic disorders. In this study, the anxiolytic efficacy of ziprasidone was evaluated in nonpsychotic subjects who were anxious before undergoing minor dental surgery. We compared a single oral dose of 20 mg ziprasidone (N = 30) with that of 10 mg diazepam (N = 30) and placebo (N = 30) in a randomized, parallel-group, double-blind study. The peak anxiolytic effect of ziprasidone compared with that of placebo was similar to that of diazepam but had a later onset. At 3 hours postdose, the anxiolytic effect of ziprasidone was significantly greater than that of placebo (p < 0.05) and somewhat greater than that of diazepam. Diazepam showed a significantly greater anxiolytic effect than placebo at 1 hour (p < 0.05) but not at 3 hours. The sedative effect of ziprasidone was never greater than that of placebo, whereas that of diazepam was significantly greater than that of placebo 1 to 1.5 hours postdose. Ziprasidone was generally well tolerated. Only one patient reported treatment-related adverse events (nausea and vomiting) and, unlike diazepam, ziprasidone did not cause reductions in blood pressure. Dystonia, extrapyramidal syndrome, akathisia, and postural hypotension were not seen with ziprasidone. Thus, ziprasidone may possess anxiolytic effects in addition to its antipsychotic properties.
 ...
PMID:The anxiolytic effect of the novel antipsychotic ziprasidone compared with diazepam in subjects anxious before dental surgery. 1191 Feb 68

Ziprasidone is a novel antipsychotic which, in oral formulation, has been shown to be effective and well tolerated in the treatment of acute psychosis. This pilot study examined the efficacy and tolerability of the intramuscular (IM) formulation and the transition from IM to oral ziprasidone in patients with acute schizophrenia. The study design was an open, prospective, 5-day treatment trial of IM ziprasidone followed by oral dosing in 12 patients with acute exacerbation of schizophrenia. Various doses (2.5, 5, 10, or 20 mg) up to 60 mg/day total were administered over 3 days, followed by transition to oral ziprasidone on Days 4-5. All patients completed the study. Mean improvements between baseline and Day 3 were observed in Brief Psychiatric Rating Scale (47.8 to 28.9) and Clinical Global Impression of Severity (6.1 to 5.3), and improvements were maintained on Days 4 and 5. No extrapyramidal syndrome, acute dystonia, or serious adverse events were reported. In these patients, IM ziprasidone 20-60 mg/day reduced psychomotor agitation and other symptoms of psychosis. The transition from IM to oral ziprasidone was well tolerated. Copyright 2000 John Wiley & Sons, Ltd.
 ...
PMID:A pilot study of intramuscular ziprasidone in the short-term treatment of patients with acute exacerbation of schizophrenia. 1240 21

The introduction of atypical antipsychotics represents an important advance in the treatment of schizophrenia. As their therapeutic efficacy, tolerability and safety profiles are clearly superior to classical neuroleptics, atypical antipsychotic agents are considered to be the treatment of choice in first episode patients. In addition, an increasing number of patients are being switched from classical to atypical antipsychotic agents. Switching is especially relevant in patients with a poor therapeutic response to classical neuroleptics and persistent symptoms (positive symptoms, negative symptoms, depressive syndromes, cognitive deficit); in patients with a psychotic relapse despite compliance; in patients with important side-effects (not only acute and tardive extrapyramidal symptoms [EPS] and general side-effects, but also dysphoria or neuroleptic-induced deficit syndrome [NIDS]); and in patients who are non-compliant due to side-effects. Switching to atypical antipsychotics should be performed with extreme care in stabilised patients; or in patients who present a danger to themselves or others at relapse; or in patients who are on depot neuroleptics who were non-compliant to previous oral treatment. Switching requires careful planning to reduce the risk of withdrawal effects (neuroleptic withdrawal syndrome, cholinergic rebound, exacerbation of symptoms or relapse, rebound of parkinsonism, dystonia, akathisia, dyskinesia), which may mask the beneficial effects and lead to early discontinuation of the new treatment. Patients, family and carers should be actively involved at all stages, and educated about the possible benefits and problems associated with switching therapy. Cross-tapering old and new treatment is the preferred method for switching and this involves tapering off the previous antipsychotic agent and any adjunctive treatment (sedatives, anticholinergic medication), while gradually titrating the new atypical antipsychotic agent to the established therapeutic dose. Switching patients to amisulpride treatment offers effective antipsychotic therapy, with a positive effect on negative and depressive symptoms. Amisulpride treatment also results in improved quality of life and social functioning in addition to fewer relapses and days of hospitalisation during long-term follow-up.
 ...
PMID:Switching to amisulpride. 1241 9

In the course of treatment of psychiatric patients, it is often necessary to switch antipsychotic medications. In recent years, atypical antipsychotic agents have become the first-line therapeutic interventions for treating psychotic symptoms. Reasons for switching patients from the typical antipsychotics to the atypical agents can include enhanced efficacy against negative symptoms, improvement in cognitive capacity, and reduction of risk of extrapyramidal side effects. The presumed long-term benefits of switching to the new antipsychotic drug should be assessed. Pharmacokinetic and pharmacodynamic properties of antipsychotic agents and drug-drug interactions should be considered during the switch process. Two methods are employed for the switch process: crossover ("crosstitration") and an abrupt switch. With the crossover method, the patient's current medication is tapered over a period of several days to several months to prevent potential withdrawal symptoms, such as nausea, vomiting, insomnia, muscle aches, and diaphoresis. Due to withdrawal symptoms, clozapine is the only atypical agent recommended to proceed with a slow dose taper when switching to another atypical drug. Sudden cessation could also precipitate the emergence of motor symptoms, which can include pseudoparkinsonism, dystonia, akathisia, and dyskinesia. The initiation of the new antipychotic occurs concurrently with the tapering of the previous drug. In an abrupt switch, the previous antipsychotic is discontinued suddenly, independent of its dose, and the new antipsychotic is started on the next day. Both methods have been used in clinical practice and double-blind studies. To date, only two medications have been studied in large multicenter clinical trials. These are olanzapine and ziprasidone. The olanzapine study revealed optimal benefits when the previous agents were gradually withdrawn and olanzapine was initiated at 10 mg/day. The ziprasidone switch study demonstrated both reduced adverse side effects from the previous agents and improvements in clinical efficacy. Additional studies are needed to examine the optimal methods for switching patients from one atypical agent to another atypical antipsychotic.
 ...
PMID:Clinical significance of drug binding, protein binding, and binding displacement drug interactions. 1247 62

Although it is often perceived as a paediatric disorder, significant numbers of patients with Niemann-Pick disease type C present for the first time in adult life or survive into adult life. The presentation in these patients differs from that seen in the classical juvenile form of the disease. Adult patients are often referred to clinicians with psychosis or other major psychiatric problems. The dystonia with preserved intellectual functioning can be mistaken for other basal ganglia disorders such as Wilson disease. The presence of vertical gaze palsy is an important clinical clue and, in the presence of a modest increase in plasma chitotriosidase activity, can be very helpful in the differential diagnosis. The diagnosis should be confirmed in suspected cases by filipin staining of cultured fibroblasts, as well as cholesterol esterification studies and DNA mutation analysis.
 ...
PMID:Niemann-Pick disease type C in adults. 1255 42

Tardive dystonia is an uncommon form of chronic dystonia, which usually develops on exposure to neuroleptics. Tardive dystonia (Tdt) following lithium therapy has not been previously reported. The case of 38 year old man with bipolar affective disorder who developed tardive dystonia while on maintenance lithium treatment is described. Presentation of Tdt in this patient was fairly characteristic although there was no suggestion of recent neuroleptic exposure. Tdt known to have poor treatment response, responded very well to clozapine, a novel anti-psychotic, in this case. To conclude, Tdt may develop on exposure to drugs other than neuroleptics. An adequate trial to clozapine can prove to be a useful treatment option.
 ...
PMID:Lithium - induced tardive dystonia. 1257 99

Niemann-Pick disease type C (NPC) is an autosomal recessive neurometabolic disorder that rarely presents in adulthood, and is associated with cognitive decline, various movement disorders (ataxia, chorea, dystonia, and myoclonus), a vertical supranuclear gaze palsy (VSGP), and seizures. A recent case report demonstrated a delay in diagnosis of eight years when a patient with NPC presented with psychosis. This article reviewed all cases seen at the Mayo Clinic with a possible diagnosis of NPC between 1976 and 2000. Of the 52 possible cases, five had an established diagnosis of adult onset NPC. Of these, two presented with psychosis and were not diagnosed with NPC for 5 and 15 years, respectively. NPC may initially present in adulthood with psychosis, and when psychosis is associated with VSGP, various dyskinesias, and seizures, NPC should be suspected.
 ...
PMID:Adult onset Niemann-Pick disease type C presenting with psychosis. 1264 83

Xanomeline is a muscarinic M(1)/M(4) preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects (EPS) at therapeutically relevant doses. In the present study, we examined whether the xanomeline-induced functional dopamine antagonism found in rodent studies could also be observed in nonhuman primates. In addition, we studied whether the lack of EPS observed in rodents also applies to primates. To this end, we investigated the effects of xanomeline on the behavior induced by D-amphetamine and (-)-apomorphine in drug-naive Cebus apella monkeys. Antipsychotic compounds antagonize amphetamine-induced motor unrest and stereotypies in this species. Xanomeline inhibited D-amphetamine-induced motor unrest, stereotypies and arousal as well as apomorphine-induced stereotypies and arousal in drug-naive Cebus apella monkeys. Xanomeline did not induce EPS but vomiting occurred in some monkeys at high doses, in accordance with emetic events observed in Alzheimer patients following xanomeline administration. Even when xanomeline was tested in EPS-sensitized Cebus apella monkeys, EPS were not observed at the dose range of xanomeline used in the D-amphetamine-apomorphine combination study (0.5-3 mg/kg). However, when xanomeline was tested at 4 mg/kg, moderate dystonia was seen in two out of three monkeys. It is concluded that xanomeline inhibits D-amphetamine- and (-)-apomorphine-induced behavior in Cebus apella monkeys at doses that do not cause EPS. These data further substantiate that muscarinic receptor agonists may be useful in the pharmacological treatment of psychosis.
 ...
PMID:The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys. 1270 Jul 11

Mutations in the parkin gene, PARK2, are a common cause of parkinsonism in familial as well as isolated cases with an age of onset <40 years and should be considered in the diagnostic work up of young-onset parkinsonism. We report a detailed clinical evaluation of a personal series of 24 patients with mutations in the parkin gene. The clinical presentation of most cases was broadly comparable to that of previous descriptions of autosomal recessive early-onset or juvenile parkinsonism and young-onset Parkinson's disease and also had similarities with phenotypes of dopa-responsive dystonia. However, our only case with consanguineous parents had an age of onset of 54 years. We report three new phenotypes at presentation: cervical dystonia; autonomic dysfunction and peripheral neuropathy; and pure exercise-induced dystonia. We emphasize a number of clinical features that can be seen in parkin disease: focal dystonia; early instability; freezing; festination or retropulsion; concurrent autonomic failure; dramatic response to anticholinergics; early or atypical L-dopa-induced dyskinesias; exquisite sensitivity to small doses of L-dopa; and recurrent psychosis, even taking L-dopa alone. We also report behavioural disorder prior to the onset of parkinsonism. Some relatives carrying a single parkin mutation without extrapyramidal symptoms or signs also had psychiatric symptoms that might be related to their carrier status.
 ...
PMID:Parkin disease: a phenotypic study of a large case series. 1276 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>