摘要:

Acute ischaemic stroke is a leading cause of mortality and morbidity around the world. An arterial occlusive lesion is found in the majority of patients with acute ischaemic stroke, and recanalisation has been shown to result in a better clinical outcome. The only widely approved recanalisation strategy is the use of intravenous alteplase (recombinant tissue-type plasminogen activator; tPA) within 3 hours of stroke onset. However, this therapy has limitations, and alternative or supplemental recanalisation strategies need to be considered in a large number of patients with acute ischaemic stroke. One such promising strategy is intra-arterial thrombolysis.This article reviews the pharmacology of the various drugs used for intra-arterial thrombolysis in the setting of acute ischaemic stroke and the results of the clinical trials that have studied their benefit. Three generations of thrombolytic agents have been available for clinical use so far. The first-generation agents such as streptokinase and urokinase were the first to be studied in acute stroke, and a number of positive case reports and series of their intra-arterial use have been reported from around the world. Second-generation products include alteplase and pro-urokinase. The clinical benefits of intra-arterial pro-urokinase were recently proven in a randomised, placebo-controlled study. Third-generation agents, such as reteplase, lanoteplase and tenecteplase, offer superior recanalisation rates with limited systemic adverse effects and might prove to be the agents of choice for intra-arterial acute stroke thrombolysis in the future. The exact administration regimens as well as the identification of patient sub-populations most likely to benefit from intra-arterial thrombolysis are subjects of current investigations, and hopefully firmer guidelines will be established in the next few years, once the results of the clinical trials are available.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Fatigue is a common disabling symptom of multiple sclerosis (MS). It is often considered a state of exhaustion distinct from depressed mood or physical weakness. Fatigue can be assessed by either self-report scales or performance-based measures; however, neither method captures all features of fatigue. Fatigue in MS frequently leads to unemployment. It is associated with a sense of loss of control over one’s environment, low positive affect, psychological distress and neurological impairment. To date there is no reproducible neuroimaging marker or biological correlate that has been identified.Proposed pathological mechanisms of fatigue in MS include neuronal factors such as dysfunction of premotor, limbic, basal ganglia or hypothalamic areas; disruption of the neuroendrocrine axis leading to low arousal; alteration in serotoninergic pathways; changes in neurotransmitter levels; and altered CNS functioning caused by a disruption of the immune response.Treatment of fatigue is best approached in a multidisciplinary fashion that incorporates nonpharmacological interventions as well as medication. Amantadine and modafinil are among the most commonly used medications for fatigue associated with MS. Both medications have been studied with positive results in controlled clinical trials. Additional research towards measurement and pathogenesis of fatigue will hopefully lead to improved therapies.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Propofol (Diprivan®1) is a phenolic derivative with sedative and hypnotic properties but is unrelated to other sedative/hypnotic agents. Formulated as an oil-in-water emulsion for intravenous use, it is highly lipophilic and rapidly crosses the blood-brain barrier resulting in a rapid onset of action. Emergence from sedation is also rapid because of a fast redistribution into peripheral tissues and metabolic clearance. The depth of sedation increases in a dose-dependent manner.In well designed clinical trials in patients receiving sedation in the intensive care unit (ICU) for a variety of indications, propofol provided adequate sedation for a similar proportion of time to midazolam, but the rate of recovery was faster with propofol. Even after periods of prolonged sedation (>72 hours), propofol was generally associated with a faster time to recovery than midazolam. Propofol facilitated better predictability of recovery and an improved control of the depth of sedation in response to titration than midazolam. In patients sedated following head trauma, propofol reduced or maintained intracranial pressure.Propofol is associated with generally good haemodynamic stability but induces a dose-dependent decrease in blood pressure and heart rate. Bolus administration may cause transient hypotension, and slow initial infusions are recommended in most patients. Serum triglyceride concentrations should be monitored during prolonged infusions (>3 days) because of the risk of hypertriglyceridaemia. The administration of 2% propofol can reduce this risk. Strict aseptic technique must be used during the handling of the product to prevent accidental extrinsic microbial contamination.Despite a higher acquisition cost with propofol, most studies of short-term sedation (approximately <3 days) showed that overall costs were lower with propofol than with midazolam, because a faster time to extubation reduced total ICU costs. However, as the period of sedation increased, the cost difference decreased.ConclusionThe efficacy of propofol in the sedation of adults in the ICU is well established, and clinical trials have demonstrated a similar quality of sedation to midazolam. Because of a rapid distribution and clearance, the duration of action of propofol is short and recovery is rapid. Emergence from sedation is more rapid with propofol than with midazolam, even after long-term administration (>72 hours), which enables better control of the depth of sedation in response to titration and more predictable recovery times. Thus, for the ICU sedation of adults in a variety of clinical settings, propofol provides effective sedation with a more rapid and predictable emergence time than midazolam.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

▴ The atypical antipsychotic agent clozapine is associated with a lower propensity for extrapyramidal symptoms than classical antipsychotic agents.▴ The pharmacokinetics of clozapine are affected by wide interpatient variability and a potential for drug interactions. Some studies have shown a relationship between plasma concentrations, duration of treatment and antipsychotic clinical response.▴ Clozapine (mean 274.2 mg/day; n = 490) had a greater preventive effect on suicidality among patients with schizophrenia or schizoaffective disorder at high risk for suicide than olanzapine (mean 16.6 mg/day; n = 490) in a randomised, rater-blinded, multicentre study (p < 0.05; a 22–24% improvement).▴ Other prospective noncomparative trials of the effects of clozapine on suicidal ideation or attempts endorsed these results, while results from retrospective trials are equivocal.▴ Clozapine is commonly associated with sedation, hypersalivation, tachycardia, dizziness, constipation and orthostatic hypotension. Agranulocytosis, diabetes mellitus and weight gain may also occur.Table. Features and properties of clozapine (Clozaril®)

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

The management of neurological and psychiatric disorders is a vast and evolving area for researchers, primary care physicians and specialists. To help you keep up to date with the latest advances worldwide on all aspects of drug therapy for neurological and psychiatric disorders, this new section of the journal brings you information selected from the drug therapy reporting serviceInpharma Weekly1. The following reports are selected from the latest issues, summarising the most important research and development news, clinical studies, treatment guidelines, pharmacological, pharmacoeconomic and adverse drug reactions/interactions news, and expert opinion pieces published across a broad range of literature sources.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS