摘要:

Tacrolimus (FK506) and cyclosporin (cyclosporin-A) are potent immunosuppressants which are presently in clinical use for the treatment of allograft rejection. Recent studies suggest that tacrolimus and cyclosporin may also be of therapeutic benefit for the treatment of neurodegenerative disorders, in particular those associated with acute brain ischaemia. At immunosuppressive doses, tacrolimus is a powerful neuroprotectant in many experimental models of cerebral ischaemia: reducing infarct volume and improving neurological outcome. In rat focal ischaemia models neuroprotection can be elicited by a single injection of tacrolimus given up to 72 hours before or up to 2 hours after the insult. A similar postocclusion window of efficacy has been reported in the gerbil forebrain ischaemia model. These neuroprotective properties are also shared by cyclosporin, although the poor penetration of cyclosporin across the blood-brain barrier necessitates the use of high doses (20 mg/kg) of this drug to achieve neuroprotection. The observation that sirolimus (rapamycin) is not neuroprotective in models of focal cerebral ischaemia, but can effectively inhibit the neuroprotective effects of tacrolimus, supports the view that the protective effects of tacrolimus are mediated via the inhibition of calcineurin.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Postdural puncture headache (PDPH) is an infrequent, but troubling, syndrome following therapeutic or diagnostic dural puncture. The classic feature of PDPH is its postural nature: worse when upright and relieved when supine. Other findings such as visual and auditory changes, nausea, vomiting, neck pain and cranial nerve palsies may occur. The syndrome typically occurs 1 to 3 days following dural puncture. The pathophysiology is related to leakage of CSF, with resultant cerebral traction and reflex vasodilation. PDPH is more common in young patients.Prevention is most important, and can be achieved by using the smallest possible noncutting spinal needles. Bed rest is not necessary following dural puncture as a preventative measure.Treatment options include bed rest, oral analgesics and epidural blood patch (EBP). Prompt use of EBP is usually warranted if no symptomatic relief is apparent within 48 to 72 hours. Prolonged symptoms, especially if the patient is unresponsive to EBP, should prompt consideration of other aetiologies of headache.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Lamotrigine has been used to treat over a million patients worldwide, including about 4000 adults and over 1000 children in clinical trials. It is a valuable broad spectrum drug that is well tolerated and has few adverse effects apart from skin rash. Most of the rashes are mild but some severe, life-threatening skin reactions have been reported. The available evidence does not indicate that either the mild or the severe skin rashes are any more common with lamotrigine than with carbamazepine, phenytoin or phenobarbital (phenobarbitone).In vitrolymphocyte transformation tests suggest that an immune mechanism is involved.The incidence of rash with lamotrigine can be reduced by using starting doses and dose-escalation rates that are no higher than those recommended, especially in patients who are receiving comedication with valproic acid (sodium valproate), which prolongs the half-life of lamotrigine. Consideration might be given to using even lower dose schedules than those currently recommended to reduce the incidence of rash further.Any patient who develops a rash or who becomes unwell in the first few weeks of treatment should be evaluated promptly by a physician. Lamotrigine should be stopped immediately if the rash or illness could be attributed to the drug. Reintroduction after initial rash has been achieved but is not recommended without close specialist supervision and should not be undertaken if the initial reaction was serious. Details of serious reactions should be reported to the appropriate national drug safety agency to provide information that will allow further improvements in the risk/benefit ratio.Extensive data have shown that lamotrigine is a valuable anticonvulsant drug that has few adverse effects if it is used correctly.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

The mesolimbic dopaminergic system functions as a major reward pathway in the CNS and is an appropriate target for antidepressant drugs. This review describes the principal features of drugs such as amfebutamone (bupropion) which activate the mesolimbic system without inducing strong neuroadaptation and are therefore useful in the treatment of retarded (or inhibited) depression. The short latency of clinical action makes these drugs particularly suitable for the treatment of patients with severe depression or those who are poorly compliant with other medications. Additional dopaminergic antidepressants include minaprine and amisulpride. The latter drug potentiates dopaminergic transmission through an atypical mechanism, i.e. the inhibition of dopamine autoreceptors controlling the synthesis and release of dopamine. Finally, a number of drugs that are not considered as classical ‘dopaminergic’ antidepressants, such as tricyclic antidepressants or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors, can also affect dopaminergic transmission, as indicated for example by their ability to induce changes in brain dopamine receptor density. This further supports the importance of central dopaminergic transmission in the pathophysiology of depression.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

As a consequence of its prevalence, early onset and chronicity, schizophrenia imposes clinical and economic impediments to healthcare practitioners. Among the armamentarium of agents available to treat the symptoms of this devastating illness, the atypical antipsychotics have received a great deal of attention. Although these agents have proven valuable, their use has often been limited as a result of high acquisition costs relative to the older conventional antipsychotics. This review examines the relevant literature concerning the pharmacoeconomics of clozapine, risperidone and olanzapine, and incorporates the findings into a discussion enveloping the general principles of pharmacoeconomics.Comparisons of the pharmacoeconomic studies of atypical antipsychotics often resulted in inconsistent findings because of differences in methodologies, outcome measurements and perspectives. While all 3 antipsychotics improved clinical outcomes, the literature suggests that clozapine is cost effective in patients with treatment-refractory symptoms, whereas risperidone and olanzapine may be cost neutral. One finding that emerged repeatedly with these drugs is that they consistently reduce hospitalisation costs as a result of a decrease in the rate of hospital admission and duration of stay (although this does not always translate into a reduction in overall costs).More than ever, healthcare practitioners and decision-makers alike are faced with the challenge of providing quality care while balancing fiscal responsibility. Further pharmacoeconomic studies on atypical antipsychotics are necessary to facilitate the practitioner in meeting these challenges.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS