摘要:

The neurotransmitter &ggr;-aminobutyric acid (GABA) activates more than one receptor subtype, including the metabotropic receptor, GABAB. GABABreceptors are located at pre- and postsynaptic sites on central neurons and mediate changes in the membrane conductance of potassium and calcium ions. This influences transmitter release as well as affecting neuronal activity directly.The GABABsystem can be modified by receptor ligands. This is currently exploited clinically, within the spinal cord, with the use of the GABABagonist baclofen to treat spasticity and, to a lesser degree, trigeminal neuralgia. However, other potential uses of GABABligands may be on the horizon in relation to absence epilepsy, cognitive impairment and depression.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Opioid intoxication is one of the most common causes of drug-related emergency department visits in the developed world. Successful treatment requires the timely recognition of intoxication, early airway intervention and the judicious use of an antidote (usually naloxone), when appropriate.During the last decade, naloxone treatment strategies have undergone substantial evolution. This has resulted largely from the recognition that the treatment of the opioid intoxicated patient must differ from that of the patient recovering from physician-controlled anaesthesia in the operating room or procedure suite. The use of standard administration of naloxone by paramedics in the field or physicians in the emergency department is often either ineffective or produces unwanted opioid withdrawal in opioid-tolerant patients. Also, in the setting of polysubstance overdose or trauma, the use of naloxone may have deleterious effects. Current management strategies emphasise the need for individualised therapy for opioid-intoxicated patients.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Obsessions, compulsions and rituals have been recognised as abnormal cognitions and behaviours for several centuries. These symptoms and signs, which have been variously referred to in different ages and cultures, are encompassed under the present diagnosis of obsessive-compulsive disorder (OCD).OCD has been an elusive nosological entity, resistant to treatment until the last 30 years. In 1966, two distinct treatment modalities, a potent serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SRI) and behavioural therapy, were introduced. Today, SRIs and behavioural therapy remain important interventions in modern OCD management, underscoring the fact that more effective modes of treatment have not been developed. Despite recent advances in understanding the underlying neurobiology of OCD, its treatment remains a challenge.At present, the mainstay of treatment is a combination of pharmacotherapy and behavioural therapy. In terms of pharmacotherapy, the most effective class of medication remains the SRIs. Clomipramine and the selective SRIs fluoxetine, fluvoxamine, paroxetine and sertraline have all demonstrated efficacy and are regarded as first-line agents for monotherapy. If multiple trials of SRIs do not result in improvement, alternative monotherapy may be attempted with monoamine oxidase inhibitors, buspirone or clonazepam. If monotherapy achieves partial response, augmentation of SRIs or combinations of agents may be considered. Only haloperidol has demonstrated efficacy as an augmentation of an SRI in a controlled trial and only in patients with comorbid tic disorders. There is support from noncontrolled trials for some other augmenting agents.Of the psychotherapeutic techniques, only behavioural therapy in the form of exposure and response prevention (ERP) has demonstrated significant effectiveness. Optimal results in the management of OCD are often realised through a combination of ERP and pharmacological therapy, although the availability of behavioural therapy is limited.For the small proportion of patients who are severely disabled by prolonged treatment-resistant OCD, neurosurgery may be an effective treatment option.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Neurobiological and neuropharmacological theory and findings have encouraged trials of pharmacotherapies in the rehabilitation of patients with neurological and neuropsychological disorders. Among the latter, pharmacological enhancement of the rehabilitation of aphasia appears promising, as neurolinguistic research has provided clues to the functional-anatomical deficits underlying aphasic symptoms. At present, few clinical studies in this area have been conducted. Furthermore, most of those that have been performed were unblinded, involved only small numbers of patients, or were limited by deficits in patient description, group homogeneity, experimental design or evaluation.However, there is evidence that the use of central stimulants and piracetam may result in an enhancement or acceleration of improvement in addition to training. Bromocriptine, a dopaminergic agent, may improve nonfluency when it is combined with speech therapy. However, none of these effects can yet be considered as established. On the basis of modern neurolinguistics, target symptoms for investigations of symptom-specific pharmacological approaches can be defined.At present, antidepressant treatment can be recommended in aphasic patients who are clinically depressed, a significant minority of patients.Often, the choice of drug will be determined by the adverse effect profile. On the basis of animal models, certain drugs such as haloperidol and clonidine should be avoided in patients receiving neurological or neuropsychological rehabilitation.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

There is now considerable evidence that a number of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, are characterised by a chronic, but silent, inflammatory process in affected brain regions. There are also many epidemiological studies indicating that anti-inflammatory drugs may inhibit the onset and slow the progression of Alzheimer's disease.The cytokines are important modulators of inflammation, and evidence is beginning to accumulate that many occur at abnormal levels in brain regions affected by disease or injury. A number of cytokines, like many other inflammatory system proteins, are made by brain cells. At present, the available information is generally fragmentary, but the field of cytokines may offer new areas for therapeutic intervention in neurological diseases. Some success has already been reported in multiple sclerosis.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Iohexol is a water-soluble nonionic contrast medium, commonly used in diagnostic radiography of the brain and spinal cord. Although its diagnostic efficacy is similar to that of other iodinated contrast media, its tolerability profile is generally better than that of ionic and older nonionic media. Iohexol causes fewer neurotoxic events than ionic media and some nonionic agents (metrizamide) in patients undergoing myelography. Patient discomfort is, moreover, reduced after intravascular injection of iohexol compared with the ionic agents diatrizoate, metrizoate and iothalamate in neuroangiography. Iohexol has been used successfully in a small number of patients with previous anaphylactoid reactions without serious untoward effects.In common with other newer nonionic agents, iohexol is generally more expensive than conventional ionic media. Nonionic agents are, however, routinely used in myelography and neuroangiographic investigations, where the risk of attendant adverse events is especially high; ionic agents are no longer used in myelography.In conclusion, iohexol offers a similar diagnostic efficacy profile to that of other nonionic agents. Wider clinical experience is, however, required to determine whether tolerability differences exist between iohexol and other newer agents of this class. Nevertheless, iohexol should be considered a first-line contrast medium in neurological imaging procedures.Pharmacodynamic PropertiesIohexol is a water-soluble, low osmolality, nonionic iodinated contrast medium, routinely used in neurological imaging procedures of the brain and spinal cord. Adverse responses seen after intrathecal or intravascular injections of iohexol are thought to be governed by its chemical and physical properties. Osmolality, for example, plays an important role.Intrathecal injection.The development of nonionic contrast media (such as metrizamide and iohexol) brought about significant reductions in neurotoxicity compared with the older ionic agents, particularly after intrathecal use. Collective data fromin vitroandin vivoanimal studies suggest that iohexol is less likely to produce epileptogenic effects than ionic (diatrizoate, ioxaglate) and some nonionic agents (metrizamide and iopamidol). EEG abnormalities and detrimental changes in cognitive function and mood occurred less frequently in patients undergoing myelography with iohexol than with metrizamide. Iohexol produced no histological evidence of arachnoiditis in animals.Intravascular injection.All iodinated contrast media produce some form of haemodynamic or rheological change when injected. Iohexol causes less vasodilation than high osmolality ionic media; this generally manifests as warmth, heat or pain. Although red blood cell deformation has not been reportedin vitro,iohexol may cause erythrocyte aggregation. Leucocyte function may also be impaired. The anticoagulant effects of nonionic media are generally less pronounced than those of ionic agents. Nephrotoxicity is an important consideration in the elderly or in patients with underlying renal disease or diabetes mellitus undergoing neuroangiography.Pharmacokinetic PropertiesIohexol is absorbed from CSF into the systemic circulation after intrathecal injection. Peak iodine blood concentrations occur immediately after rapid intravenous injection and within 2 to 6 hours after intrathecal administration.Iohexol binds poorly to plasma proteins. Animal studies indicate that iohexol does not significantly cross the intact blood-brain barrier after intravascular administration. Some diffusion across the placental barrier probably occurs, although it is unclear to what extent iohexol is excreted in breast milk. Volume of distribution averages 0.56 L/kg after intrathecal administration and 0.17 L/kg after intravenous injection of iohexol.Iohexol is not significantly metabolised, deiodinated or biotransformed. It is eliminated by renal excretion; approximately 90% of an injected dose is excreted in urine within the first 24 hours after administration. The terminal elimination half-life of iohexol ranges from approximately 2 to 8 hours after an intrathecal dose. Vascular compartment half-life is approximately 20 minutes.Elimination of iohexol may be delayed in patients with renal impairment; extrarenal excretion (into bile) may occur in these individuals. Iohexol can be removed by haemodialysis.Diagnostic EfficacyRegardless of the procedure used (myelography or neuroangiography), iohexol produces excellent to good radiographic visualisation of the spinal cord/brain in >80% of patients. Similar findings have also been reported in a small number of children undergoing myelography. Nondiagnostic or suboptimal radiographs generally resulted from technical problems, underlying pathology or patient movement, rather than from the opacity of the contrast medium itself.Comparative studies demonstrate that the diagnostic efficacy of iohexol is similar to that of other ionic (diatrizoate, iothalamate, ioxaglate and metrizoate) and nonionic (iodixanol, iopamidol, iopromide, iotrolan and metrizamide) agents. Because of their neurotoxic effects, ionic agents are no longer used in myelography; both types of contrast medium may, however, be used in selected patients undergoing neuroangiography.TolerabilityNonionic agents produce fewer complications than ionic agents.Myelography.Headaches, mild to moderate pain (including backache), neckache and stiffness, and nausea and vomiting occur most frequently after intrathecal administration of iohexol. Symptoms generally occur within the first 24 hours after the procedure, are mild to moderate in severity and transient (usually disappearing within several days). Seizures have been reported rarely. The frequency and severity of adverse events appears to depend on several factors, including gender, age, radiographic technique, medical history and clinical findings. A similar profile of adverse events is seen in adults and children.Comparative data suggest that iohexol is generally better tolerated than metrizamide. Findings from other studies comparing iohexol with iotrolan or iopamidol are, however, inconclusive.Neuroangiography.Adverse events after intravascular administration of iohexol are usually mild to moderate, transient and occur within 24 hours of the procedure. Sensations of warmth are reported most frequently; other commonly described events include pain, visual disturbances, headaches and nausea. Cardiovascular and other CNS events (including paraesthesia, transient global amnesia and seizures) have also been documented in individual patients. Specific tolerability data in children undergoing neuroangiography are unavailable.Iohexol has been used successfully without serious untoward effects in a small number of patients who had previously experienced anaphylactoid reactions. These individuals should be pretreated with antihistamines or corticosteroids.Findings from comparative studies show that iohexol produces less patient discomfort (warmth) than diatrizoate, metrizoate and iothalamate. Results from studies investigating nonionic agents are, however, less conclusive.Dosage and AdministrationIohexol is available in solutions of varying iodine concentrations: 140, 180, 210, 240, 300 and 350 mg/ml. The volume and concentration of iohexol used for a diagnostic procedure depend on the degree and extent of contrast required for the examination and on the equipment and technique used.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS