摘要:

In addition to the systemic renin-angiotensin system (RAS), a local RAS has been identified. Recent research has focused on this latter system and has investigated the effects of locally generated angiotensin II, especially in the kidney, heart and CNS.In the mammalian brain, all components of the RAS are present including angiotensin AT1and AT2receptor subtypes. While the AT1receptor is responsible for the classical effects of angiotensin II, it has been found that the AT2receptor displays totally different signalling mechanisms and this has revealed hitherto unknown functions of angiotensin II. AT2receptors are expressed at low density in many healthy adult tissues, but are up-regulated in pathological circumstances, e.g. stroke or nerve lesion.Evidence has now emerged that the actions of angiotensin II that are exerted via the AT2receptor are directly opposed to those mediated by the AT1receptor. For example, the AT2receptor has antiproliferative properties and therefore opposes the growth-promoting effect linked to AT1receptor stimulation. It has been reported that the AT2receptor regulates several functions of nerve cells, e.g. ionic fluxes, cell differentiation and axonal regeneration, but also modulates programmed cell death.It is possible that a more extensive knowledge of the AT2receptor could contribute to the understanding of the clinically beneficial effects of AT1receptor antagonists, as this treatment may unmask AT2receptor activity. This review presents selected aspects of advances in AT2receptor pharmacology, molecular biology and signal transduction with particular reference to possible novel therapeutic options for CNS diseases.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Polytherapy with antiepileptic drugs is not popular mainly because it is thought to be associated with more adverse effects and to contribute relatively little in terms of efficacy compared with monotherapy. However, there are two reasons to question this assumption:certain combinations are more effective than others and, therefore, generalisations about the poor effectiveness of polytherapy cannot be made; andthe total drug load, i.e. the total amount of drug exposure for a certain indication, is usually higher in polytherapy, which may explain the higher toxicity seen during such treatment.In this article, the available literature on the effectiveness of first-line monotherapy, alternative monotherapy and second-line polytherapy is reviewed. There is no conclusive evidence in favour for choosing either alternative monotherapy or polytherapy when first-line monotherapy fails. Therefore, a pragmatic approach is recommended until an evidence-based choice can be made.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Long-term administration of antipsychotics occasionally produces persistent dystonia of the trunk, a disorder known as Pisa syndrome (or pleurothotonus). The development of Pisa syndrome is most commonly associated with prolonged treatment with antipsychotics; however, it has also been reported, although less frequently, in patients who are receiving other medications (such as cholinesterase inhibitors and antiemetics), in those not receiving medication (idiopathic Pisa syndrome) and in those with neurodegenerative disorders.Drug-induced Pisa syndrome predominantly develops in females and in older patients with organic brain changes. It sometimes occurs after the addition of another antipsychotic to an established regimen of antipsychotics or insidiously arises in antipsychotic-treated patients for no apparent reason. The condition generally disappears after antipsychotic drugs are discontinued. Although a pharmacological therapy for drug-induced Pisa syndrome has not been established, we have reported that anticholinergic drugs are effective in about 40% of patients who have episodes of Pisa syndrome with the remaining patients responding to the withdrawal or reduction of daily doses of antipsychotic drugs.The characteristics of its development and prognosis indicate that drug-induced Pisa syndrome consists of two types of dystonia. Some patients develop clinical features of acute dystonia, whereas others develop symptoms similar to tardive dystonia. Like that of tardive dystonia, Pisa syndrome responds better than tardive dyskinesia to a relatively high daily dose of an anticholinergic. However, the significant improvement caused by the withdrawal of antipsychotic drugs in Pisa syndrome differentiates it from tardive dystonia. Thus, Pisa syndrome including these features is considered to be an atypical type of tardive dystonia.These clinical characteristics suggest that the underlying pathophysiology of drug-induced Pisa syndrome is complex. A dopaminergic-cholinergic imbalance, or serotonergic or noradrenergic dysfunction, may be implicated. Asymmetric brain functions or neural transmission may also be considered as underlying mechanisms of the development of Pisa syndrome that is resistant to anticholinergic drugs.Idiopathic Pisa syndrome is characterised by an adult-onset, segmental truncal dystonia in patients with no previous exposure to antipsychotics. It occurs rarely but shows a complete resolution with high doses of anticholinergic drugs.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Selective mutism is a multidimensional childhood disorder in which, according to the most recent studies, biologically mediated temperament and anxiety components seem to play a major role. Several psychotherapy methods have been reported in case studies to be useful, but the disorder is commonly seen to be resistant to change, particularly in cases of long duration. Currently, behaviour modification and other cognitive methods, together with cooperation with the family and the school personnel, are recommended in the treatment of selective mutism. Selective serotonin reuptake inhibitors and selective monoamine oxidase inhibitors have also been reported to be helpful when treating children with selective mutism. At the moment, pharmacotherapy cannot be recommended as the treatment of first choice but if other methods of treatment are not helpful, medication can be included in the treatment scheme. Comprehensive evaluation and treatment of possible primary and comorbid problems that require treatment are also essential.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Clinical trials of therapies for acute migraine attacks have evolved over the years from open-label, small observational studies to highly structured randomised, controlled trials. The International Headache Society Committee on Clinical Trials in Migraine developed a tool to guide in designing scientifically sound trials. The proof of effect is best achieved in a clinical trial with:clearly defined objectives;a well-characterised study population, identified using well-validated diagnostic tools;proper randomisation and blinding;inclusion of a placebo arm, with proper balancing of patients receiving placebo and those receiving active drug;adequate study power; andappropriate statistical methods.Both parallel and crossover studies may be suitable in clinical trials of antimigraine agents, although the latter are a better choice in patient preference and bioequivalence studies.Although various efficacy measures are used to assess treatment effect, the 2-hour pain free rate (total resolution of pain within 2 hours after an initial moderate to severe headache) is preferred because it is clinically relevant and is relatively ‘placebo-insensitive’. Various migraine surveys have indicated that a rapid onset of therapeutic effect is a highly desirable attribute of an antimigraine drug. Therefore, accurate measurements of treatment effect before 2 hours are becoming increasingly emphasised.Consistency of effect across multiple attacks adds to the understanding of the therapeutic efficacy of a test drug. Finally, preference and satisfaction studies allow us to assess patients' global impression of a particular treatment, weighing the positive effects on pain and associated symptoms of migraine against potential adverse effects.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but potentially fatal, adverse reaction that occurs in patients, including children, who are treated with anticonvulsants. During metabolism of the anticonvulsant, toxic arene-oxide compounds are produced. AHS is associated with both cutaneous and systemic symptoms and is associated with multiorgan involvement. Liver damage, in particular, seems to be associated with fatal outcomes.The pathophysiology of AHS is still uncertain but it may be linked to a genetically determined inability to detoxify reactive drug metabolites.The prompt recognition of the first clinical signs of AHS, and the rapid withdrawal of the anticonvulsant, often avoids the progression of symptoms.Pharmacological treatment is essentially based on systemic corticosteroids in association with enteral nutrition, intravenous fluid augmentation, pain relief and ocular care. Intravenous immunoglobulins may also have a possible therapeutic role in some cases. Diagnostic tests, such as patch tests orin vitroassays, for AHS could help to identify patients at risk of developing the syndrome and could represent a first step of primary prevention when applied to relatives of patients.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Amisulpride, a substituted benzamide derivative, is a second-generation (atypical) antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3autoreceptors. At higher doses, amisulpride antagonises postsynaptic D2and D3receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission.In patients with acute exacerbations of schizophrenia, the recommended dosage of amisulpride is 400 to 800 mg/day, although dosages ≤1200 mg/day may be administered. In comparative trials, amisulpride administered within this range (400 to 1200 mg/day) was as effective as haloperidol 5 to 40 mg/day, flupenthixol 25 mg/day and risperidone 8 mg/day in patients with acute exacerbations of schizophrenia with predominantly positive symptoms. Amisulpride was more effective than haloperidol but equally effective as risperidone in controlling negative symptoms. Amisulpride 400 to 800 mg/day was more effective than haloperidol, risperidone and flupenthixol in controlling affective symptoms in these patients.In randomised, double-blind trials involving patients with predominantly negative symptoms of schizophrenia, amisulpride 50 to 300 mg/day was more effective than placebo.Amisulpride is effective as maintenance therapy in patients with chronic schizophrenia. Long-term treatment with amisulpride was associated with improvements in quality of life and social functioning.Amisulpride is generally well tolerated. In well-controlled trials, the neurological tolerability profile (including ratings on extrapyramidal symptom scales) of amisulpride 400 to 1200 mg/day was superior to that of the conventional antipsychotics (haloperidol or flupenthixol), but was similar to that of the atypical antipsychotic risperidone. At low dosages of amisulpride (≤300 mg/day), the incidence of adverse events (including extrapyramidal symptoms) reported with amisulpride was similar to that with placebo.Conclusion: In comparative trials, amisulpride 400 to 1200 mg/day showed efficacy in reducing overall symptomatology and positive symptoms similar to that of conventional antipsychotics and newer atypical antipsychotics in patients with acute exacerbations of schizophrenia. Moreover, its effective alleviation of negative and affective symptoms, its lower association with extrapyramidal symptoms and loss of cognitive function than conventional antipsychotics and its long-term efficacy justifies consideration of the use of higher dosages of amisulpride in this group of patients. Consequently, the dosage of amisulpride that is recommended in patients with acute exacerbations of schizophrenia is 400 to 800 mg/day, although dosages ≤1200 mg/day may be administered. Lower dosages of amisulpride (50 to 300 mg/day) should be considered for the management of patients with negative symptoms of schizophrenia. Amisulpride is a first-line treatment option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS