摘要:

Current usage of the term ‘atypical’ in relation to antipsychotics lacks clear theoretical underpinnings and rigour in application. The prevailing definition of atypicality is a reduced liability to induce extrapyramidal side effects (EPS). However, this definition appears incomplete in the face of numerous other limitations associated with antipsychotics that can impact adversely on patient well-being; these encompass issues of efficacy, non-motoric physiology and quality of life.On this basis, more conservative, operationalised criteria for atypical antipsychotic activity can be offered and applied to representative classical versus more recently introduced antipsychotics. These criteria include a reduced liability to induce EPS, but also superior efficacy, efficacy in patients who do not respond to classical antipsychotics, and no induction of subjective dysphoria, sedation, autonomic/cardiac effects, sexual dysfunction and bodyweight gain, and no elevation of prolactin levels or other endocrine effects. Such criteria codify yet higher aspirations for treatment with the welcome array of newer agents that is currently emerging.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Until recently, antipsychotic drugs were assumed to be generally equivalent in terms of efficacy while adverse effects varied along a relative continuum. Particular compounds did not stand out as being qualitatively different. With the introduction of clozapine, discussions of novel or atypical effects began, and now there is debate as to what criteria should be used to define atypicality. I would argue that the term has served a heuristic function, but is no longer useful.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Practical guidelines for plasma concentration monitoring of anticonvulsants are necessary to ensure the appropriate and cost-effective use of these drugs. The guidelines should be based on clinically relevant considerations and recommendations for the drug treatment of epilepsy, including the choice of drugs.Immunoassays are the methods of choice in many laboratories engaged in therapeutic drug monitoring. This assay type has several advantages over other currently used methods, being a precise, reproducible and rapid method for determination of anticonvulsants in micro samples. However, it does not have the same screening potential as chromatographic methods, which can also be used for determination of less common anticonvulsants and new drugs.For several anticonvulsants, there is a more or less well defined therapeutic plasma concentration range. This range, however, must not be strictly interpreted, because many of the studies on which these ranges are based involved patients with severe epilepsy who were treated with several anticonvulsants. Nevertheless, most patients are optimally treated with a drug when steady-state plasma concentrations are maintained within that range. Further studies are necessary to determine the place of plasma concentration monitoring of the newer anticonvulsants.There are several pitfalls in plasma concentration monitoring of anticonvulsants. In practice, the use of plasma drug concentrations requires considerable interpretative skills, a common problem being the interpretation of the therapeutic range.In recent years, plasma concentration monitoring in general has attracted criticism, with suggestions that drug concentrations are being measured unnecessarily or interpreted incorrectly. It is, therefore, of utmost importance that these measurements be requested only on the basis of sound clinical judgement. This will enable therapeutic drug monitoring to be kept as a valuable tool to be used when attempting to treat individual patients most effectively and with the fewest adverse effects.The development and testing of new anticonvulsants should include an evaluation of plasma concentration monitoring as early as possible in the course of development. Specially designed clinical studies should be used, preferably in patients receiving monotherapy.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Cerebral malaria is a potentially fatal manifestation of ‘severe’ malaria caused byPlasmodium falciparum.It is an especially important problem for African children because it is a major cause of death due to malaria. The pathophysiology of cerebral disease is characterised by complex host-parasite interactions. Optimal management of cerebral malaria is also complex, requiring accurate diagnosis, prompt treatment with one of the few remaining effective antimalarial drugs, and recognition that cerebral disease is frequently accompanied by other major organ dysfunction requiring additional care.Three classes of antimalarial drugs are useful for cerebral malaria: the 4-aminoquinolines (chloroquine), the cinchona alkaloids (quinine, quinidine) and the artemisinin compounds (artesunate, artemether). Chloroquine is the drug of choice in the few areas of the world where the falciparum parasite remains sensitive. In most malarious regions, however, the cinchona alkaloids and the artemisinin compounds are the only remaining options. In some areas of Southeast Asia, resistance to quinine is established, further limiting treatment options and raising concerns for the future. Artemisinin compounds, an exciting new class of antimalarial drugs developed in China, are the most rapidly acting of all the antimalarial drugs, with little known toxicity. Despite new insight into the pathogenesis of cerebral malaria and powerful antiparasitic therapies, the mortality rates in patients with this disease have remained stable over many years and are unacceptably high, ranging from 10 to 50%. Thus, malaria remains a tremendous public health problem that requires continued efforts to better understand pathophysiology and develop more effective therapies.The best way to prevent cerebral malaria is to prevent infection with P.falciparum.Most approaches are based on a chemoprophylactic regimen in combination with other measures such as repellents and insect screens. Even though no regimen is completely effective, chemoprophylaxis may reduce the subsequent risk of cerebral malaria if a ‘breakthrough’ falciparum infection is acquired. Additionally, early diagnosis and prompt treatment of individuals with uncomplicated falciparum malaria may diminish the risk of cerebral malaria.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Pharmacological treatments have been used in an attempt to improve the memory dysfunction induced by electroconvulsive therapy (ECT). Despite promising results from animal studies, human studies report few successes. Piracetam and physostigmine have been reported to directly improve memory test scores. The use of caffeine and liothyronine (triiodothyronine; T3) has been reported to reduce the number of ECT treatments required to produce a therapeutic effect, thus indirectly reducing memory deficits. However, the majority of studies on pharmacological treatments report no success.Some studies suggest that reducing the dosage of medications regularly administered with ECT may reduce memory deficits. However, reducing these medications may not be fruitful as they are necessary to prevent the medical risks associated with ECT. Moreover, at the dosages used during ECT, these medications have not been consistently shown to adversely affect cognition.At present, better controlled studies are required to assist in the search for effective pharmaceutical agents to reduce the cognitive deficits associated with ECT.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

This review highlights recent pharmacological and clinical advances in the understanding of the potential use of serotonin 5-HT2receptor antagonists as treatments for a number of psychiatric disorders, namely anxiety, depression and schizophrenia.5-HT2receptor antagonists have not yet been clearly demonstrated to be effective in humans as treatments for anxiety. Some preliminary clinical trials suggest that the 5-HT2receptor antagonist ritanserin may have a beneficial effect in patients with generalised anxiety disorder, but the evidence is far from compelling.Upregulation of central 5-HT2receptors and an accompanying increase in phosphoinositide turnover appear to be predisposing biological factors in depression. A functional interaction between 5-HT1Aand 5-HT2receptors may be of particular importance, since 5-HT2receptor antagonism can ultimately result in a facilitation of 5-HT1Areceptor-mediated neurotransmission and this may be beneficial for the treatment of depression. Ritanserin appears to be more effective than placebo in alleviating the depressive symptoms of dysthymia. Nefazodone is a new antidepressant that combines 5-HT2receptor blockade with serotonin reuptake inhibition. Comparisons with imipramine favour nefazodone in terms of tolerability and suggest that both drugs are equally clinical effective.In schizophrenia, 5-HT2Areceptor function appears to be altered. Modulation of dopaminergic function via 5-HT2Areceptors may provide a viable mechanism for enhancing the effect of antipsychotics. Risperidone, the first post-clozapine agent that has 5-HT2Aand dopamine D2receptor antagonist actions, is at least as effective as haloperidol and perphenazine in reducing acute psychotic symptoms. Its major clinical advantages are a greater efficacy in controlling the secondary negative symptoms and a lower incidence of extrapyramidal symptoms (EPS). The efficacy of ritanserin in alleviating both positive and negative symptoms in acutely psychotic patients seems to support the hypothesis that potent 5-HT2Areceptor antagonism alone may contribute to the therapeutic action of several clinically effective antipsychotics that have reduced liability to induce EPS.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

▴ Talipexole is a dopamine D2receptor agonist, with activity at both pre- and postsynaptic D2receptors. The drug also has &agr;2-adrenoceptor agonist activity.▴ In a primate model of Parkinson's disease, talipexole dose-dependently improved motor activity and parkinsonian symptoms, and beneficial effects were additive when combined with levodopa.▴ Clinical trials with talipexole in patients with Parkinson's disease demonstrated statistically significant improvements from baseline for parkinsonian symptoms including akinesia, rigidity, tremor and gait disturbances.▴ In a large comparative trial in patients with Parkinson's disease, talipexole was associated with a higher response rate and a lower incidence of gastrointestinal adverse events than bromocriptine, although drowsiness was more common among talipexole recipients.▴ The most frequently reported adverse events associated with talipexole are drowsiness, dizziness, hallucinations and minor gastrointestinal complaints such as nausea, gastrointestinal discomfort and loss of appetite.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS