摘要:

There is a body of experimental and anecdotal evidence to suggest that thrombolytic therapy may be useful in reducing morbidity and mortality after acute ischaemic stroke. A series of clinical trials designed to test hypotheses concerning risk and benefit have now been published. Intravenous streptokinase when given within 6 hours of ischaemic stroke may be of marginal benefit when given alone, but of no benefit when given with aspirin (acetylsalicylic acid) because of an unacceptably high early mortality. There is a trend toward much better outcomes if streptokinase is given early (<3 hours post-stroke). Intravenous alteplase (tissue plasminogen activator; tPA) has a much better risk-benefit profile than streptokinase, particularly when given within 3 hours of a stroke at a dose of 0.9 mg/kg. Indeed, this dose was recently approved for use by the US Food and Drug Administration.Any planned administration of thrombolytic therapy to patients with acute ischaemic stroke should be in centres with experienced staff and facilities to monitor clinical progress. Further trials are needed to identify which thrombolytic agents, time windows of administration and dosages provide the best riskbenefit ratios.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

In an effort to improve survival in patients with high-grade brain tumours, it was hypothesised that local delivery of carmustine (BCNU) to these tumours would prolong survival. By implanting a polymer impregnated with carmustine into the tumour resection cavity, it was hoped that high local drug concentrations could be achieved over a sustained time period with minimal systemic concentrations or toxicity.This hypothesis was tested in the laboratory, and the use of a carmustine polymer was found to be safe and efficacious in a rodent brain tumour model. Based on the preclinical laboratory studies, a series of clinical studies were carried out to evaluate the safety and efficacy of this treatment.Two phase III randomised, placebo-controlled studies have been completed evaluating the use of a carmustine polymer in patients at the time of recurrence and as initial therapy. Both studies demonstrated that carmustine polymers resulted in prolonged survival. These studies establish the principle that local delivery by a polymer is an efficacious drug delivery strategy. Furthermore, these studies demonstrate that local delivery of carmustine by the polymer is an effective treatment for patients with high-grade gliomas.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

The nature of preoperative anxiety appears to vary from patient to patient, and the natural course of the condition has not been well evaluated. In clinical studies, the incidence of preoperative anxiety has varied widely, from 11 to 80%, depending on the methods used to assess it. Because there appears to be a relationship between high preoperative level of anxiety and greater surgical risk, attempts to measure and relieve presurgical anxiety seem to be of clinical significance.There are several problems with the designs and methods used in past and more recent studies of premedication. Many of the recent results were produced from studies that used a variety of more or less validated assessments, yielding variable results in different centres which can seldom be compared with each other. More accurate and generally accepted but simple assessments are needed to studying the anxiolytic effect of different premedicants.Benzodiazepines are the most popular preoperative agents because their anxiolytic effect is associated with high patient acceptance and they are devoid of significant adverse effects. However, great interindividual variation in response does occur. It is likely that new methods of administering benzodiazepines (such as by intranasal, transmucosal and rectal routes) could increase the utility of these agents.The preoperative anxiolytic effect of antipsychotics, antihistamines and barbiturates is questionable, but some opioids and especially &agr;2receptor agonists appear to have this property. However, clinically significant unwanted effects may prevent the routine use of the latter 2 drug groups.It should be noted that all patients do not automatically require pharmacological premedication. Good preoperative information, assurance and a positive attitude of hospital personnel may be the best treatment for preoperative anxiety in some cases.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Dementias are a significant cause of morbidity and mortality in developed countries. Although the key diagnostic factor that defines the dementias is a sustained loss of cognitive ability, dementias are also frequently accompanied by debilitating behavioural disturbances. These behavioural disturbances cause significant problems for the caregivers of people with dementia and are major factors precipitating institutionalisation.The pathophysiological relationship between cognitive and behavioural disturbances has not been well studied. In Alzheimer's disease, the major cause of dementia, behavioural problems can occur during all stages of cognitive impairment, from mild to severe. In vascular dementia, the second largest cause of dementia, behavioural problems are less predictable due to the variable course of this disease.Following a differential diagnosis of the causes of behavioural disorders, nonpharmacological and pharmacological interventions may be required. Low dosages of antipsychotics remain the mainstay for treatment of these disturbances. Although there are no known differences in efficacy among the typical antipsychotics, careful consideration of the adverse effects of these drugs must be made on a case-per-case basis. The atypical antipsychotics clozapine and risperidone are currently being studied for this indication.Non-antipsychotic medications such as &bgr;-blockers, lithium, benzodiazepines, antidepressants, anticonvulsants, buspirone and hormonal therapy have also been tried, with mixed results. Of these, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor antidepressants are the most promising treatments. The cognitive enhancer tacrine may be effective for the management of some behavioural disturbances, but this is still being evaluated.Nonpharmacological interventions are often recommended prior to starting a medication. Behavioural management techniques are based on the systematic review and manipulation of antecedents and/or consequences of the target behaviour. A number of algorithms have been proposed for the management of behavioural disturbances, but, as yet, there are no evidence-based approaches available. However, current research is concentrating on the phenomenology and subtypes of behavioural disturbances.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

New pharmacological treatments for opioid dependence include detoxification agents such as clonidine and lofexidine, and maintenance agents such as levacetylmethadol (levo-&agr;-acetylmethadol; LAAM) and buprenorphine. Detoxification from opioids has been facilitated by the development of clonidine, particularly in combination with naltrexone. New experimental approaches have also been tried to reduce the time that it takes to complete the process of detoxification or to further reduce residual withdrawal symptoms not completely relieved by clonidine. Maintenance on levacetylmethadol or buprenorphine has become a viable alternative to methadone maintenance and holds promise for the future.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Acute extrapyramidal symptoms (EPS), specifically the motor syndromes of parkinsonism, acute akathisia and acute dystonia, are among the most common adverse effects of antipsychotic medication. They produce physical disability and subjective distress, interfere with psychosocial and occupational adjustment, confound the clinical assessment of psychiatric symptoms, and lead to poor compliance with medication.Parkinsonism, akathisia and dystonia can also be chronic conditions in patients receiving long term antipsychotic treatment. However, the most common movement disorder seen in such patients is tardive dyskinesia. The presence of the obvious movements of this condition can stigmatise patients. In the more severe cases, disability may be directly related to the particular movements, with interference with mobility, respiration, speech, eating, difficulty swallowing and possibly an increased risk of choking.To tackle acute EPS, the clinician will need to consider modifying the dosage of conventional antipsychotics or switching to a new antipsychotic that has a lower liability for these problems. If adjunctive drug therapy is considered necessary, the choice will depend partly on the particular extrapyramidal syndrome exhibited by the patient and partly on the adverse effect profiles of the possible treatments.Anticholinergic (i.e. antimuscarinic) agents are widely used in psychiatric practice to treat and prevent EPS. However, there are hazards with these drugs, including a risk of abuse and toxic confusional states, anticholinergic adverse effects (such as dry mouth, blurred vision, tachycardia, constipation, and urinary hesitation and retention) and cholinergic rebound phenomena on withdrawal. In the light of these problems, it has been recommended that anticholinergic agents are not routinely administered for the prophylaxis of EPS, unless there is a history of acute dystonia or known susceptibility to these antipsychoticinduced motor phenomena. Indeed, the evidence from published studies supports the value of anticholinergic drugs as treatment for EPS rather than for prophylaxis.Despite the efficacy of anticholinergic drugs, not all EPS are equally responsive to this treatment. The tremor and rigidity of parkinsonism are reliably relieved by these agents. However, this syndrome is known to abate spontaneously over time. After 3 months, the majority of patients initially requiring treatment with anticholinergics can have this therapy withdrawn without a relapse of parkinsonian symptoms. Therefore, anticholinergics should be periodically withdrawn to test the need for their continued prescription.Acute dystonic reactions are also effectively treated with anticholinergic drugs. In severe cases, intravenous or intramuscular administration can provide relief in minutes. The place of anticholinergics in the treatment of tardive dystonia is less clear, as only a proportion of patients will show any benefit.Anticholinergics also have an uncertain reputation in both acute and chronic akathisia, being of limited efficacy. Acute akathisia may respond best to anticholinergics if it is accompanied by parkinsonism, in which case both syndromes may improve.Anticholinergic drugs are not effective in alleviating tardive dyskinesia. The evidence suggests that these agents can sometimes worsen the movements, and when discontinued, a modest improvement may be seen in a proportion of patients exhibiting this condition. However, it has not been established that patients receiving antiparkinsonian medication in addition to antipsychotic medication are at a greater risk of developing tardive dyskinesia.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

▴ Nefiracetam (DM 9384) is a pyrrolidone derivative with potential for use in patients with dementia secondary to cerebrovascular disorders or Alzheimer's disease.▴ It is thought to act by normalising dysfunctional acetylcholine,&ggr;-aminobutyric acid (GABA) and possibly monoamine neurotransmitter systems, but it may also facilitate N/L-type calcium channel opening.▴ Nefiracetam for 2 to 12 months improved cognitive function and psychiatric symptoms in patients with dementia due to cerebrovascular disorders.▴ Nefiracetam was at least as effective as idebenone and was superior to placebo in patients with cerebrovascular dementia in large double-blind 8-week trials.▴ Adverse events as reported in clinical trials are infrequent and are mainly gastrointestinal in nature.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS