摘要:

The history of monoamine oxidase (MAO) inhibitors (MAOIs) is full of controversy, due to their interactions with certain foodstuffs and other drugs.The most feared interaction of MAOIs is the interaction with tyramine, a compound contained in a number of foods and beverages. This interaction may lead to hypertensive crises, the so-called ‘cheese reaction’. According to studies in healthy volunteers, selective reversible inhibitors of MAO-A (RIMAs) interact less with tyramine than nonselective irreversible MAOIs. Furthermore, the risk of interaction between tyramine and RIMAs seems to be lower than that between tyramine and irreversible MAOIs. In addition, the tyramine content of foods and beverages is lower than has previously been thought.Because no systematic clinical or naturalistic assessment of risk has been performed, the results of studies of food (and drug) interactions with MAOIs in healthy volunteers must be interpreted with caution. In patients with high individual sensitivity to the pressor effect of tyramine, or in those who consume large amounts of tyramine-containing foods and beverages, the cheese reaction may occur even with RIMAs. Dietary restriction of the type and amount of some foods and beverages may be necessary in elderly patients and in patients with cardiovascular diseases.As with the irreversible MAOIs, RIMAs may interact with over-the-counter remedies (containing dextromethorphan, phenylephrine and ephedrine). However, because of the more selective effects of RIMAs. theoretically, these interactions may be less frequent and less severe than those with other MAOIs. RIMAs may have the advantage in anaesthesia that discontinuation of these drugs 2 weeks before surgery may not be necessary.Despite the data accumulated to date, an accurate assessment of food and drug interactions with RIMAs requires more widespread use of the drugs. As such, the real risk of interactions may not be known with certainty for some time.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Recent clinical and epidemiological studies have estimated that 20 to 58% of patients with schizophrenia also have a diagnosis of substance abuse (i.e. have a ‘dual diagnosis’). In these patients, alcohol (ethanol), cannabis and psychostimulants are the drugs that are preferentially abused. Compared with other schizophrenic patients, those with a dual diagnosis were found to show more positive symptoms, and to have a higher risk for psychotic relapse and noncompliance with drug treatments.Benzodiazepines, and possibly carbamazepine, are recommended for detoxification in patients with dual diagnosis. In the initial treatment of psychosis in these patients, potent antipsychotics that have few anticholinergic adverse effects, such as haloperidol, should be given. For long term treatment, depot antipsychotics can be used to increase compliance rates. Since patients with a dual diagnosis are especially susceptible to tardive dyskinesia, clozapine is a possible alternative to other antipsychotics. Antiparkinsonian medication and antidepressants are other drugs to be considered.There is some evidence that flupenthixol (not available in the US) counteracts both psychosis and the craving for alcohol and cocaine. Disulfiram should be avoided for relapse prevention because of the risk of exacerbation of psychosis. Methadone or specific anticraving drugs such as naltrexone may be used in some patients.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Narcolepsy is a lifelong neurological sleep/wake disorder with a strong psychosocial impact. It is characterised by excessive daytime sleepiness and recurrent daily sleep attacks, and cataplexy (i.e. the loss of motor control upon experiencing strong emotions). This review summarises the current management options for narcolepsy, focusing on medication. It is, however, important to also consider nonpharmacological treatment aspects in order to achieve optimal results.The majority of patients need medication for the 2 main symptoms. Drugs with CNS stimulating effects, mostly of the amphetamine-type, are used to alleviate excessive sleepiness and sleep attacks. The resulting increased level of vigilance also decreases or abolishes cataplexy in a number of patients. If this is not achieved, tricyclic antidepressants, in the first instance, and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors, in the second instance, can be used to control cataplexy and other rapid eye movement (REM) sleeprelated symptoms.The number of effective medications for the treatment of narcolepsy has significantly increased during the last decades. Nevertheless, many of these are far from satisfactory. The therapeutic index of the preparations used is narrow and the responses are highly variable. However, it has been estimated that up to 80% of patients may significantly benefit from an adequate treatment.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Amyotrophic lateral sclerosis (ALS) is a degenerative neurological disorder that is manifested clinically by muscle weakness, wasting, spasticity and bodyweight loss, typically resulting in death from debilitating disease within 2 to 5 years of the onset of symptoms. Pathologically, there is degeneration and loss of the motor neurons in the spinal cord, brainstem and cerebral cortex. Over 90% of ALS cases occur sporadically (i.e. ‘primary’ ALS). The cause is unknown. There is, however, evidence that abnormalities of the excitatory amino acid glutamate are present in patients with ALS, and the possibility exists that the synaptic action of glutamate is abnormally potentiated causing excitotoxic degeneration of motor neurons. Hence, attenuation of glutamatergic transmission may provide the means for therapeutic intervention in ALS.In line with this hypothesis, several strategies for the treatment of ALS have been proposed. These include: (i) the modification of excitatory transmission mediated by glutamate using agents that can interact specifically with subtypes of glutamate receptors; and (ii) modulation of presynaptic glutamatergic mechanisms by, for example, decreasing glutamate release from nerve endings, enhancing removal of glutamate from the synapse, and augmenting glutamate metabolism by synaptic astrocytes.Some of the newer anticonvulsants can attenuate excitatory transmission by decreasing glutamate release and, therefore, these agents have therapeutic potential in ALS. Of these, riluzole has been tested in a sizeable number of patients and found to be effective in prolonging their survival by 2 to 3 months.These results raise the cautious optimism that this strategy may lead to further therapeutic gains in the near future. However, it is presently unclear whether abnormalities of glutamate are a contributing rather than a causative factor in the pathophysiology of ALS, and, as such, a better understanding of the extent of glutamatergic dysfunction in ALS neurodegeneration may lead to improved rational therapies for this disorder.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

An increased understanding of the pathophysiological consequences of stroke and, in particular, the notion of an ischaemic penumbra in acute cerebral infarction has led to the development of novel neuroprotective treatments. These act at different stages of the pathophysiological cascade that leads to ischaemic neuronal damage.A bewildering number of potentially neuroprotective treatments are currently in preclinical and clinical development. This article systematically reviews all the completed and ongoing randomised controlled trials evaluating the effect of the more recently developed neuroprotective agents on clinical outcomes in patients with acute stroke. These agents are focused on because more detailed quantitative meta-analyses are available for many of the earlier neuroprotective agents.A simple classification of all the current neuroprotective agents on the basis of common potential mechanisms of action is presented. The agents are classified into 8 major groups: modulators of excitatory amino acids, modulators of calcium influx, metabolic activators, antioedema agents, inhibitors of leucocyte adhesion, free radical scavengers, promoters of membrane repair and those with an unknown mechanism of action.The data emerging from clinical trials of currently available neuroprotective therapies have not provided clear evidence of the benefit of this type of treatment. Further large randomised trials involving patients with both ischaemic and haemorrhagic stroke are required before the routine use of neuroprotective therapy in clinical practice can be recommended.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

▴ Tolcapone is an orally active specific inhibitor of peripheral catechol-O-methyltransferase (COMT), which has therapeutic potential as an adjunct to levodopa in the treatment of patients with Parkinson's disease.▴ Accumulation of 3-O-methyldopa, the inactive metabolite of levodopa formed by COMT, has been associated with reduced transport of levodopa into the brain and also with the ‘wearing-off’ phenomenon.▴ Plasma levodopa concentrations are increased, and 3-O-methyldopa concentrations are decreased, when tolcapone is coadministered with levodopa/carbidopa, levodopa/benserazide or levodopa alone.▴ Coadministration of tolcapone and levodopa (in most instances plus benserazide or carbidopa) increased the duration of ‘on’ time in patients with Parkinson's disease.▴ Tolcapone allowed the dose and frequency of administration of levodopa (alone or with carbidopa) to be reduced.▴ Preclinical studies indicate that tolcapone may have antidepressant activity.▴ Tolcapone was generally well tolerated, with few reported adverse events.

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