摘要:

In contrast to more traditional antipsychotic drugs such as haloperidol, atypical antipsychotics such as clozapine are characterised by low levels of extrapyramidal side effects (EPS) and improved clinical efficacy. This may result from increased binding to dopamine D4and serotonin 5-HT2Aand 5-HT2Creceptors concomitant with decreased dopamine D2receptor blockade, particularly of D2sites in the striatum where EPS are thought to originate.Although there is no genetic evidence for a direct role of variation in the D4receptor gene in schizophrenia, a role for variation in the 5-HT2Areceptor gene is supported by genetic and biochemical studies. This does not preclude the D4receptor as a major therapeutic target for antipsychotic drugs, especially since it is expressed predominantly in the cortex and limbic system, where the antipsychotic effects of drugs such as clozapine are thought to be mediated.As novel serotonin-dopamine receptor antagonists with defined pharmacological profiles become available, the careful analysis of the relationship between receptor binding profiles and efficacy will determine the most important receptor targets for improved antipsychotic action without the generation of EPS. Furthermore, the role of D4receptors as therapeutic targets will soon be determined by the use of selective ligands about to be introduced into clinical trials.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

This article provides guidelines on the treatment of nicotine dependence and tobacco addiction that are based on the recent US Agency for Health Care Policy and Research (AHCPR) Smoking Cessation Clinical Practice Guideline.Nicotine replacement therapy should be encouraged for most patients in the absence of specific contraindications, as it has been shown to be efficacious in increasing abstinence rates in smoking cessation. Although 4 types of nicotine replacement therapy (transdermal patch, polacrilex chewing gum, spray and inhaler) have been shown to be effective, the transdermal nicotine patch is associated with fewer patient compliance problems and/or adverse effects.Clinician-provided social support and skills-training/problem-solving techniques are also effective components of smoking cessation treatment. Smoking cessation interventions of this type that are as brief as 3 minutes are effective in producing both short and long term abstinence, although rates of quitting are higher with more frequent and intensive treatments.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Most of the adverse effects of opioid analgesics are related to effects on the CNS. This article reviews the causes and treatment of the most frequent CNS adverse effects of opioid analgesics prescribed for the relief of cancer-related pain. Such effects can occur during short term treatment of opioid-naive patients (e.g. sedation, nausea, vomiting, respiratory depression, mood changes, difficult micturition) and during long term treatment of patients in chronic pain (e.g. delirium, hyperalgesia, generalised myoclonus, tonic-clonic seizures), and can be classified according to their clinical relevance.The symptoms can be associated with high concentrations of opioids and their metabolites in CSF, but can also be caused by pharmacological interactions between opioids and other drugs commonly used in clinical practice. Moreover, they may be related to the accumulation of active metabolites in patients with renal impairment.Opioid rotation, hydration of the patient and suspension of drugs that can interfere with the pharmacokinetics of opioids are suggested approaches to treatment. Psychostimulants can be used to treat opioid-induced sedation. Naloxone can be used to reverse severe respiratory depression caused by high doses of opioids. Haloperidol and midazolam are useful for the treatment of opioid-induced hyperactive delirium.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Stroke prevention using antiplatelet agents is now a routine part of therapy in patients with transient ischaemic attack (TIA) or stroke. Aspirin (acetylsalicylic acid) is the most widely used agent. Other agents with clinically established efficacy are ticlopidine and dipyridamole.Despite its widespread use, the efficacy of aspirin is modest, being approximately 15 to 18% in major placebo-controlled trials of the prevention of stroke. The optimal antithrombotic dosage of aspirin for stroke prevention has not been established from a direct comparison of dosages in patients with TIA or stroke. At present, the most frequent recommendation is a dosage of between 100 and 300 mg/day. However, it has not been proven whether very low dosages (30 to 50 mg/day) or dosages as high as 1300 mg/day offer slight, marked or no major benefit with regard to the prevention of a first or recurrent stroke. There is some evidence indicating the lack of a relationship between aspirin dosage and gastrointestinal haemorrhages and haemorrhagic stroke, but a relationship does exists between dosage and gastrointestinal symptoms and withdrawals due to adverse effects.Ticlopidine has proven to be more effective than aspirin in reducing the risk of stroke in patients with TIA and stroke. Patients who do not tolerate aspirin because of allergic or gastrointestinal reactions are candidates for ticlopidine. The most commonly used dosage of ticlopidine is 250mg twice a day. A new derivative of ticlopidine, clopidogrel, seems to be as effective as ticlopidine and is free from the most harmful adverse effect of ticlopidine, i.e. neutropenia.Recent data indicate that the combined use of aspirin and dipyridamole has an additive effect in patients with TIA and stroke compared with either drug alone. This combination was stated as being twice as effective as either drug alone in the second European Stroke Prevention Study.Despite encouraging data on new alternatives, aspirin is still the most widely accepted first-line treatment for the secondary prevention of stroke.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

The frequency of adverse drug interactions increases disproportionately with the increase in the number of drugs given to patients. It was shown that 40% of patients given 16 drugs experienced an adverse drug interaction, compared with 5% of patients given fewer than 6 drugs. The magnitude of the drug interaction problem increases substantially in anaesthetised patients because of: (i) the increased use of multiple drugs in the preoperative and intraoperative periods; and (ii) the growing population of geriatric patients who, in addition to having diminished drug metabolising capacity, are often prescribed multiple medications for concomitant medical illness.Drug interactions with volatile and intravenous anaesthetics can be divided into those that are pharmacokinetic and pharmacodynamic in nature. Pharmacokinetic interactions occur when the absorption, distribution, metabolism or excretion of a drug is altered by the coadministration of a second drug. Pharmacodynamic interactions involve a change in the pharmacological effect of a drug as a result of the action of a second drug at receptor sites.An interaction between drugs, if not recognised and corrected, can result in decreased drug efficacy or serious toxicity. It is essential that careful scrutiny of the patient's drug history is an integral part of the preoperative assessment.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

▴ Entacapone is a potent, orally active, selective inhibitor of peripheral catechol-O-methyltransferase (COMT), which has therapeutic potential as an adjunct to levodopa therapy in patients with Parkinson's disease.▴ Entacapone decreases peripheral conversion of levodopa to 3-O-methyldopa and improves central uptake of levodopa.▴ Addition of entacapone to levodopa/carbidopa or levodopa/benserazide increased the duration of clinical response in patients with Parkinson's disease: the duration of ‘on’ time was increased and the duration of ‘off’ time was decreased.▴ Levodopa requirements were reduced in patients with Parkinson's disease who received adjunctive entacapone therapy.▴ Entacapone was generally well tolerated, with few reported adverse events.

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