摘要:

Migraine is a prevalent condition worldwide. It has far-reaching individual and societal economic impact. Almost all migraineurs (95%) take medications for headache relief and the majority use over-the-counter (OTC) medications. OTC drugs are readily accessible, affordable and effective. These medications are commonly used without the advice of a healthcare professional, hence the potential for negative health outcomes due to improper use. To avoid these problems and their potentially harmful consequences (e.g. toxicity, adverse effects), major efforts should be directed towards educating the public about migraine and its treatment, including the appropriate use of OTC medications.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Leucocytes appear to potentiate stroke injury by clogging the microcirculation and infiltrating into the brain where they release free radicals and other substances that are toxic to neurons. Through the use of specific monoclonal antibodies directed against leucocyte adhesion receptors, both the microcirculation obstruction and the leucocyte infiltration can be decreased. Experimental studies have found reduced stroke damage through the use of antibodies that bind to either the CD18 leucocyte adhesion receptor or the corresponding endothelial cell receptor, intercellular adhesion molecule-1 (ICAM-1). These studies have shown the most benefit when anti-adhesion monoclonal antibodies are used in experimental models in which reperfusion follows an initial period of ischaemia. Based on these encouraging experimental results, a clinical trial using an anti-ICAM-1 adhesion agent has just been completed, with final results expected soon.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Psychotic disorders in childhood are rare conditions, although there are no reliable epidemiological data that could be looked upon as representative. This may be due to the fact that different investigators have used different definitions, and several heterogeneous disorders have been subsumed under the heading of ‘psychoses in childhood’. Nevertheless, it is assumed that only 0.1 to 1% of all schizophrenic psychoses manifest themselves before the age of 10 years; however, after the age of 13 years, a remarkable increase in the occurrence of schizophrenia can be observed.The prognosis, course and outcome of the very early-onset psychoses, as well as the manifestation of the disorder in adolescence, seem to be less favourable as compared with adult-onset schizophrenia. The data so far available demonstrate that premorbid personality and adaptation, the occurrence or absence of developmental delays, age at onset, gradual or acute onset, impairment of cognitive functions, and the predominance of negative symptoms along with a high load of premorbid introverted symptomatology (e.g. shyness, social withdrawal, overanxiousness) are of special relevance to the course and outcome of childhood schizophrenia.Comparable with other fields of child psychopharmacology, the treatment of young patients with psychoses is characterised by a paucity of empirical studies evaluating the efficacy and safety of drug treatments. Despite the proven efficacy of conventional antipsychotics in the short term and maintenance treatment of schizophrenia, a high proportion (about 30 to 40%) of patients with early-onset and adolescent schizophrenia are initial nonresponders to this treatment. For these patients, a trial of atypical antipsychotics such as clozapine can be considered. if strict guidelines for clinical management are followed. In childhood and adolescence, the treatment of psychoses involves a multidimensional approach, including psychopharmacological therapy, psychotherapeutic modalities, family interventions and special rehabilitation measures.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Epilepsy is the most common serious neurological condition. Overdoses with anticonvulsants are common and produce major morbidity, in many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are uncommon. Management in most cases centres on supportive measures. In general, with perhaps the exception of valproic acid (sodium valproate) and carbamazepine, the effects seen in overdose tend to be exacerbations of the adverse effects observed with lower doses of these drugs.The drugs used to treat epilepsy are diverse and come from several classes. With acute phenytoin ingestion, the predominant effects include ataxia, lethargy and nystagmus. Cardiovascular toxicity is rare after oral ingestion and patients do not require routine cardiac monitoring.Clinical signs and symptoms in overdoses of valproic acid are believed to be a combination of the effects of the parent drug and the metabolite 2-en-valproic acid. Prominent effects may include lethargy, coma, cerebral oedema, thrombocytopenia and metabolic acidosis. Cerebral oedema typically becomes clinically apparent 2 to 3 days after overdose, while the nadir of the haematological injury tends to be 3 to 5 days after overdose. Most patients who have taken an overdose of valproic acid will do well with gastrointestinal decontamination and aggressive supportive care only. Haemodialysis use must be weighed against its risks, but may prevent cerebral oedema, thrombocytopenia and prolonged coma.In overdose with carbamazepine, many of the effects seen may be related to mechanisms secondary to the tricyclic structure that the drug shares with the cyclic antidepressants. The main risks are coma, seizures, depression of respiratory drive (requiring mechanical ventilation) and ventricular arrhythmias. The management of patients with carbamazepine overdose is primarily supportive. Large overdoses may require intubation and mechanical ventilation. The risks involved in haemoperfusion suggest that this procedure is warranted only in patients with ventricular dysrhythmia or unstable cardiac status that has not responded to conventional therapies.Overdose with the succinimides is rare. The effects seen include lethargy, coma and respiratory depression. The treatment of an overdose of the succinimide derivatives is primarily supportive.Symptoms of phenobarbital (phenobarbitone) overdose are generally exacerbations of the CNS depressant effects seen with therapeutic concentrations, i.e. slurred speech, somnolence, ataxia, obtundation and coma. With severe intoxication, hypotension and depressed cardiac output may be seen. In most cases of phenobarbital overdose, the patient will do well with gastrointestinal decontamination and aggressive supportive care only. Multiple-dose activated charcoal has been shown to reduce serum drug concentrations; however, no clear improvement in clinical effects has been shown. Haemoperfusion can restore haemodynamic stability and improve the level of consciousness. However, due to the usual successful outcome of supportive therapies, the risks involved in haemoperfusion appear warranted only in patients with unstable cardiac status that has not responded to conventional therapies.The predominant toxic effects of benzodiazepines include sedation, ataxia, dizziness, slurred speech, confusion and ataxia. Significant effects, such as respiratory depression and death, are most likely to occur in the setting of co-ingestants or parenteral administration. The management of benzodiazepine overdose is primarily supportive. Routine flumazenil use in such patients should be avoided.There are limited data on the effects of the newer anticonvulsants, felbamate, gabapentin and lamotrigine, in overdose. Felbamate has produced only mild effects of agitation, ataxia and somnolence after ingestion of 10 times the recommended daily dose. Overdoses of gabapentin have produced dizziness and diarrhoea, and those of lamotrigine lethargy, ataxia and nystagmus. Clinically insignificant, but mild, cardiovascular toxicity of sinus tachycardia and widened QRS interval has also been reported with lamotrigine overdose. The treatment of the newer anticonvulsants in overdose is essentially supportive after decontamination with activated charcoal.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

The negative symptoms of schizophrenia comprise one of several identified symptom clusters associated with the disorder. Although consensus on the precise components of the negative syndrome and on definitions for specific negative symptoms have not been reached, for the purpose of this review, negative symptoms include blunted affect, poverty of thought content and speech, apathy, social withdrawal and anergia. Negative symptoms are among the most disabling and treatment-resistant symptoms of schizophrenia, and various approaches to treatment have been taken, including augmentation of conventional antipsychotic treatment with antidepressants.Assessment of the effect of treatments on negative symptoms can be problematic and, therefore, clinical trials need to be of adequate duration and systematic attempts need to be made to rule out secondary causes of negative symptoms that may mimic or exacerbate them.Placebo-controlled studies of fluoxetine and fluvoxamine, which controlled for secondary negative symptoms, have demonstrated substantial improvement in negative symptoms compared with placebo. Significant exacerbation in psychotic symptoms was not reported in these controlled trials. This, therefore, represents a promising clinical option for treating negative symptoms.It appears that the maximum benefit of antidepressant augmentation may not be achieved until at least 12 weeks after initiation of therapy. Therefore, trials of shorter duration may understate the potential efficacy of this combination.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

This review provides a comparison of conventional [phenobarbital (phenobarbitone), phenytoin, primidone, carbamazepine, ethosuximide and valproic acid (sodium valproate)] and newer (felbamate, oxcarbazepine, zonisamide, vigabatrin, gabapentin and lamotrigine) anticonvulsants.The advantages and disadvantages of the older agents are well documented, because they have been administered to large numbers of patients for prolonged periods of time. A complete assessment of the adverse effects of the newer agents is not yet possible because of the relative lack of experience with them, such that the potential for infrequent adverse reactions or reactions occurring only after long term use is unknown.Common early adverse effects (i.e. acute toxicity) mainly affect the CNS. Sedation or drowsiness are associated with phenobarbital, primidone and zonisamide, and sometimes with vigabatrin and gabapentin, usually transiently with the latter 2 drugs. Dizziness, vertigo, diplopia and motor incoordination characterise the acute toxicity of phenytoin and carbamazepine, and can occur when lamotrigine is coadministered with carbamazepine. Drug-induced stupor or coma is a rare adverse effect of valproic acid and vigabatrin. The initiation of treatment with several anticonvulsants can be followed by an increase in seizure frequency. However, true drug-induced seizures tend to only occur in patients with particular epileptic syndromes.Gastrointestinal disturbances are more frequent after initiation of primidone, valproic acid and ethosuximide than other anticonvulsants. Leucopenia and increases in liver enzyme levels are frequent with all anticonvulsants, but usually are without clinical significance.Rare early adverse reactions mainly involve a hypersensitivity syndrome, most often limited to a skin rash. Skin eruptions have been reported to occur with all the anticonvulsants, and are probably benign in most cases. However, potentially fatal reactions are possible. Toxic acute fulminant liver failure has been associated with exposure to valproic acid, mainly in polymedicated infants with particular epilepsies, and to felbamate.CNS effects after long term administration of anticonvulsants are common. Sedation, drowsiness, fatigue and dizziness are common consequences of phenobarbital, primidone and zonisamide therapy. Other anticonvulsants usually produce minimal sedation. Lamotrigine may cause insomnia in adults. Phenytoin may slow motor functioning. Occasionally, phenytoin and valproic acid have been responsible for a subacute encephalopathy presenting as a reversible dementia. Movement disorders of various types are also a rare adverse reaction to all conventional anticonvulsants, although only valproic acid-induced tremor is of clinical significance. Behavioural changes and acute psychosis may result from the use of barbiturates, valproic acid and vigabatrin.Anticonvulsant-related leucopenia has various significance. Aplastic anaemia has been reported secondary to many conventional drugs and to felbamate, usually in polymedicated patients. Thrombocytopenia or platelet dysfunction has only been associated with valproic acid. Connective tissue disorders are a possible consequence of prolonged exposure to barbiturates or phenytoin. They have not been reported with carbamazepine or the new drugs.Increases in bodyweight are a prevalent adverse effect of valproic acid and vigabatrin, and have also been noted in patients exposed to gabapentin. Immunological disorders have to date not been associated with the newer drugs, but this may be a result of the limited experience with these agents.Phenobarbital, primidone, phenytoin and carbamazepine have been reported to induce clinical, and more often biological, signs of osteomalacia, while oxcarbazepine has not. Hyponatraemia may be a complication of carbamazepine and oxcarbazepine therapy. The other older and newer anticonvulsants do not modify electrolyte levels.All conventional anticonvulsants are metabolised in the liver, which leads to numerous more or less clinically significant drug-drug interactions. Phenytoin, phenobarbital, primidone and carbamazepine are enzyme-inducers, and valproic acid is an enzyme-inhibitor. Phenytoin and valproic acid are also highly proteinbound. Obviously, the newer agents will be easier to prescribe because of no or minimal drug-drug interactions.The older anticonvulsants are also all weak teratogenic agents. No conclusions can be drawn concerning the teratogenic potential of the newer drugs in humans, although animal data suggest that they are devoid of this effect.To date, there has been insufficient experience with new drugs in elderly patients to compare their tolerability with that of conventional agents in this patient population. Elderly patients often receive multiple medications for systemic illnesses. Therefore, they may benefit greatly from drugs, such as vigabatrin and gabapentin, that are unlikely to cause drug interactions, as well as from drugs with moderate protein binding, such as lamotrigine. Limited data suggest that the newer drugs are well tolerated in this age group, even in the presence of some decrease in hepatic or renal function.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS