摘要:

Recent evidence has been accumulating to suggest that the peptide &bgr;-amyloid may be implicated as a causative agent in Alzheimer's disease. This compound is known to accumulate in the cerebral plaques that are characteristic of the disease. Whether &bgr;-amyloid is toxicper seis yet to be established, but several options are available which may reduce the toxicity of the agent and, thus, have potential in the treatment of Alzheimer's disease.Prevention of the generation of &bgr;-amyloid from the amyloid precursor protein (APP) and inhibition of the possible neurotoxic effects of the compound are being explored. A recent finding that has gained much attention is that &bgr;-amyloid can form ion channels that are cation-specific. An increase in intracellular calcium levels can occur via these channels, which may be neurotoxic and cause inflammatory responses. The use of channel blocking agents, such as trometamol (tromethamine), may prevent neurotoxicity, while anti-inflammatory drugs may also prove to be useful therapeutic agents.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Today, benzodiazepines are the drugs most commonly involved in cases of self-poisoning. Fortunately, compared with several other drugs they are relatively safe in overdose, and symptoms of severe poisoning are rarely observed in young adults with pure benzodiazepine overdosage. However, respiratory depression, hypotension and prolonged coma are often seen in other patient groups with benzodiazepine overdosage, such as the elderly, children and patients with chronic pulmonary disease.Flumazenil, a specific benzodiazepine antagonist, is a valuable and safe diagnostic and therapeutic tool in the short term management of drug poisoning with involvement of benzodiazepines. Its use should therefore be considered in all unconscious patients admitted because of benzodiazepine overdosage.In self-poisoning, the drugs ingested are frequently a mixture of several compounds and their identity is often unknown. Flumazenil can also be used diagnostically in cases of unclear multiple drug poisoning or coma of unknown aetiology.During use of flumazenil, consideration should be paid to a few contraindications, including patients with epilepsy who are receiving long term benzodiazepine medication. Moreover, some precautions should be taken during administration, such as individual titration of the dosage to minimise the risk of inducing benzodiazepine withdrawal syndrome or unmasking toxic effects of other concurrently ingested drugs. A normal electrocardiogram recording before the antidote is given will imply a minimal risk of any adverse reactions in cases of combined intake of benzodiazepine and antidepressants. Further, the short half-life of flumazenil necessitates a period of careful supervision after its administration.Supportive care in a patient with benzodiazepine overdose includes close monitoring, preferably in the drainage position. If hypotension or prolonged CNS depression occurs, intravenous fluids should be administered. Occasionally, gastric lavage and administration of activated charcoal is indicated, but only if the patient is awake and potentially sensitive to benzodiazepines and if a large dose has been ingested within the last 1 to 2 hours.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Recent advances in the treatment of bacterial meningitis have reduced the morbidity and mortality associated with this disease. These advances include the introduction of highly active and safe extended-spectrum cephalosporins and initial adjunctive therapy with dexamethasone. For such a life-threatening illness it is obvious that rapid diagnosis and optimum supportive care are of equal importance to antibacterial and anti-inflammatory therapies. Also, prevention by active immunisation represents an attractive strategy to reduce further the impact of purulent meningitis.Third-generation cephalosporins, such as ceftriaxone and cefotaxime, are now preferred for initial therapy in most cases of bacterial meningitis. However, these agents are not active against listeria or enterococci. Moreover, pneumococcal strains resistant to both penicillin and extended-spectrum cephalosporins are becoming more prevalent.The results of recent prospective, double-blind trials of dexamethasone adjunctive therapy show that this anti-inflammatory measure improves outcome from bacterial meningitis in infants and children, and should therefore be routine. For bacterial meningitis in neonatal and adult patients final recommendations for adjunctive therapy with dexamethasone must await results of ongoing studies.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Wilson's disease results from an inherited deficit in copper metabolism. This causes a reduction of copper excretion in the bile, storage of copper in the liver, and secondary diffusion of toxic copper to the entire body. The accumulation of copper leads to the wide spectrum of clinical features of the disease, including neurological dysfunction.The role of copper in the aetiology of the disorder has been known since 1948. However, it is only recently that descriptions of candidates for a gene for Wilson's disease have been presented. It has been demonstrated that the Wilson's disease gene encodes for a copper-transporting ATPase. Other important pathophysiological findings include the demonstration that selective basal ganglia impairment may result from oxidant stress.Fortunately, effective copper-trapping therapy using chelating agents such as penicillamine and trientine, and the blockade of copper uptake by zinc and trientine were developed on the basis of clinical experience well before the pathogenesis of Wilson's disease was known in detail. Therefore, we now have 40 years of experience with drug therapy in Wilson's disease.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Approximately 20 to 30% of patients with newly diagnosed epilepsy do not have their seizures controlled with currently available antiepileptic drugs. The clinical need for new antiepileptic drugs is therefore clear.In recent years, as our understanding of the molecular basis of epilepsy has unfolded, several novel candidate antiepileptic drugs have become available for clinical evaluation. The major emphasis has been on the development of more potent and effective antiepileptic drugs, and also drugs with fewer adverse effects than existing therapies. This has resulted in 7 new drugs being licenced around the world in the last 5 years (felbamate, gabapentin, lamotrigine, oxcarbazepine, piracetam, vigabatrin and zonisamide). In addition, 7 other promising drugs are in various stages of development [eterobarb, fosphenytoin, levetiracetam (ubc L059), remacemide, stiripentol, tiagabine and topiramate].Numerous advantages over existing antiepileptic drugs can be identified for some of these new drugs. A mechanism of action has been determined for lamotrigine, tiagabine and vigabatrin. This may prove particularly useful therapeutically since it allows a more rational treatment strategy. Eterobarb, fosphenytoin, oxcarbazepine and remacemide are prodrugs. This is a particular advantage for fosphenytoin, which is metabolised to phenytoin. Gabapentin, piracetam and topiramate are not metabolised and vigabatrin is minimally metabolised. These drugs do not exhibit significant binding to blood proteins. Therefore, these drugs are not susceptible to significant pharmacokinetic drug interactions. Oxcarbazepine also exhibits minimal drug interactions. This is in contrast to felbamate, lamotrigine and stiripentol, drugs with which pharmacokinetic interactions can be clinically problematic.All drugs, with the exception of piracetam, are effective treatments for partial or secondarily generalised seizures. Piracetam and zonisamide are effective in myoclonus, and felbamate has been licenced for use in children with Lennox-Gastaut syndrome. All 14 drugs have the potential to induce adverse effects, mostly CNS-related. Whilst treatment recommendations can be made for some of the drugs, these cannot be considered definitive since they are based largely on data from controlled clinical studies in highly selected patients. Further treatment recommendations for different seizure types and epilepsy syndromes will inevitably develop as clinical experience with the drugs increases.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Adverse sexual effects of psychiatric medication can cause considerable distress to patients and so lead to noncompliance. Despite the clinical importance of psychotropic-induced sexual dysfunction, there is relatively little systematic research on its incidence and treatment. Investigation is complicated by the fact that sexual dysfunction may predate the onset of medication or may be secondary to the presenting illness. In addition, objective measures of sexual dysfunction have been difficult to construct. Few studies have attempted to combine phenomenological and physiological measures of sexual dysfunction.Nevertheless, studies suggest that sexual dysfunction is commonly seen in association with the major classes of psychotropic medication. Disturbances of erection and ejaculation are the most frequently reported sexual adverse effects of dopamine blocking antipsychotics. Antidepressant medications often lead to sexual dysfunction, with serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors commonly resulting in anorgasmia. On the other hand, certain serotonergic agents (e.g. 5-HT1Aagonists) may lead to improvement in sexual symptoms, pointing to the complexity of serotonergic mediation of sexual function.Treatment of sexual dysfunction induced by psychiatric drugs commonly involves attempting to titrate dosage, or switching from one medication to another. Certain psychotropics, such as amfebutamone (bupropion), may have few adverse sexual effects. Reversal of the dopaminergic effects of antipsychotics or the serotonergic effects of antidepressants are other strategies that may be useful. Finally, there is good evidence that adrenergic receptors mediate erection and ejaculation. As a result, there is increasing research on the efficacy of agents such as yohimbine, an &agr;2-noradrenergic antagonist, for the treatment of sexual adverse effects.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS