摘要:

Cannabinoid receptors have recently been identified in both the CNS and the periphery, and endogenous ligands for these receptors (anandamides) have been found in the CNS. Both natural and synthetic cannabinoids have promising therapeutic effects in various clinical conditions, including neurological disorders such as multiple sclerosis and Huntington's chorea. As a result of these findings, rapid progress in this new and exciting field can be expected over the next few years. This will further the understanding of the physiological role of the anandamide-cannabinoid system and allow the development of new pharmacological tools and clinically useful drugs.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Results from experimental and clinical studies indicate that antidepressants have specific analgesic properties in chronic pain. The exact site of action of these drugs (spinal or supraspinal) has yet to be established. The most likely mechanism of action of antidepressants in pain relief is via effects on monoaminergic and opioidergic systems.The most frequently postulated mechanism of action is an effect on serotonergic mechanisms: however, data are equivocal. Some data suggest that antidepressants that inhibit both serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake are the most effective agents in relieving pain, suggesting that there may be some noradrenergic involvement.The analgesic effects of antidepressants are reversed by the opioid antagonist naloxone, and changes in opioid levels are induced by these compounds. Therefore, antidepressants may also act via the opioid system. Nevertheless, direct binding of antidepressants to opioid receptors seems unlikely. Other less validated hypotheses have also been proposed. Further clinical and experimental studies are needed to better elucidate the mechanism of action of antidepressants in pain relief.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The use of antiepileptic drugs (AEDs) is associated with a wide range of drug interactions. Many of these interactions are reciprocal, i.e. both drugs affect each other. The 3 most commonly occurring clinically significant pharmacokinetic drug interactions with AEDs are: (i) induction of hepatic liver enzymes; (ii) inhibition of hepatic liver enzymes; and (iii) protein binding displacement. Clinically relevant pharmacokinetic interactions can result in either loss of efficacy or signs of toxicity.Prior to the introduction of valproic acid (sodium valproate), most of the classically used AEDs were enzyme inducers [e.g. phenobarbital (phenobarbitone), phenytoin and carbamazepine]. Valproic acid is both an inhibitor of drug metabolism and a protein binding displacer. These actions result in variable effects on other AEDs. Of the new AEDs, felbamate is an example of a drug that behaves in a similar manner to an enzyme inhibitor, but it may also have weak inducing properties. Lamotrigine has limited effects on other AEDs, but is strongly induced or inhibited by other AEDs. Oxcarbazepine, zonisamide, vigabatrin and gabapentin have either limited or no clinically significant drug interactions.As well as drug interactions between AEDs, AEDs can also interact with non-AEDs such as oral contraceptives, tricyclic antidepressants and &bgr;-adrenoceptor blockers.The time course of induction is generally gradual, as it depends on the rate of synthesis of the enzyme and the time taken to reach steady-state of the inducing drug. Drug interactions due to inhibition of hepatic drug metabolism tend to occur as soon as sufficient concentrations of the inhibitor appear in the liver, but are maximal when steady-state concentrations of the inhibitor are reached.Awareness of the potential for any drug interaction should enable the clinician to anticipate changes in patients' clinical condition that may warrant changes in therapy.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

It is generally accepted that catatonic symptoms are nonspecific and occur under different circumstances. The differential treatment of catatonic syndromes depends on their aetiology. Organic catatonia (due to an underlying neurological or metabolic condition, or intoxication), antipsychotic (neuroleptic)-induced catatonia (including neuroleptic malignant syndrome) and psychogenic catatonia (due to schizophrenia, affective disorder, neurosis or lethal catatonia) have to be distinguished.In all types of catatonia, the early detection of potentially life-threatening conditions is important. Benzodiazepines (such as lorazepam) are effective as short term treatment for symptoms associated with organic catatonia in many patients. Electroconvulsive therapy (ECT) is also effective, but limited by the attitude of the patients to this treatment and by its availability.ECT is strongly recommended in patients with lethal catatonia. The treatment of other types of psychogenic catatonia should follow the guidelines for the treatment of the underlying psychiatric condition. Antipsychotic-induced catatonia necessitates the use of anticholinergics, dose reduction of antipsychotics or change to clozapine. In patients with neuroleptic malignant syndrome, all antipsychotics must be discontinued immediately. Treatment with bromocriptine and/or dantrolene is frequently, but not unequivocally, recommended.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The optimal treatment of HIV-1-induced CNS neurological disease involves determining whether the neurological disturbance is related to HIV-1 disease itself or to an opportunistic complication. Neurological disorders associated with HIV-1 infection include AIDS dementia complex (ADC), aseptic meningitis, headache, seizures, stroke and spinal cord disease. Once the precise nature of the disturbance has been elucidated, specific treatment can be given.An important aspect of the treatment of HIV-1-related neurological diseases is that there may be a considerable time before a response is seen, usually at least several weeks. In the future, it is likely that treatment options will include more effective and less toxic antiretroviral agents. Treatment will be further enhanced by the identification of particular patients who are at risk of neurological complications of HIV-1 infection.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The intake of drugs used to treat psychiatric disorders has been used as a defence for individuals who have committed crimes. This defence has developed from the involuntary intoxication defence. Just as an individual drinking a ‘spiked’ beverage could not be held responsible for their actions while intoxicated, neither can the accused who is under the influence of prescription drugs. Because the effects of the drugs are largely unknown by the general public, their use affords such a defence.Use of drugs such as triazolam and fluoxetine has been raised as a successful defence to criminal acts, but scientific evidence appears unable to link either drug to actually causing crime. However, the use of the drug is able to negate the intent (ormens rea). With no criminal intent the accused may be able to raise a successful defence and reduce the charge and/or punishment. The Ilo Grundberg case is illustrative. Mrs Grundberg, under the influence of the benzodiazepine triazolam, murdered her mother. The defence of triazolam use succeeded, and Mrs Grundberg went on to sue the manufacturer of the drug for damages. The case was settled out of court for an undisclosed amount.A successful defence is complex and depends on many parameters, including the agent used, concomitant use of other medications, pre-existing medical conditions and the dosage of the drug(s) involved.For the accused and their legal counsel, drug-induced crime means a successful conclusion to a criminal charge. For drug manufacturers and prescribers, the relationship can lead to litigation.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

SynopsisSulpiride is a benzamide derivative, structurally distinct from other standard antipsychotics, which binds selectively to central and peripheral dopamine D2-and D3-receptors. In animals, sulpiride displays neuropharmacological and behavioural actions that are variously considered predictive of typical and atypical antipsychotic activity. Atypical properties include a lack of sedative and cataleptogenic effects and failure to antagonise apomorphine-induced stereotypy. In common with other dopamine D2-receptor antagonists, sulpiride has a pronounced prolactin-stimulating effect.Sulpiride displays an apparent spectrum of clinical activity which differs from that of conventional antipsychotics, with sedative effects predominating at higher doses and activating effects at lower doses. Antipsychotic activity occurs over a dosage range of 400 to 3200 mg/day, with negative symptoms responding best to low dosages (≤ 800 mg/day) and positive symptoms to higher dosages (≥ 1200 mg/day). In terms of its global antipsychotic efficacy, sulpiride compares similarly with most conventional antipsychotics. Extrapyramidal effects (akathisia, acute dystonia and parkinsonism) have been associated with sulpiride, occurring in 12.8% of patients receiving doses ≤ 1200 mg/day; tardive dyskinesia appears to be rare. Male impotence, galactorrhoea and amenorrhoea are presumably related to the hyperprolactinaemic effect of the drug.As a disinhibiting antipsychotic, sulpiride is indicated for the treatment of acute and chronic schizophrenia with prominent autistic and affective symptoms. The wide therapeutic dose range and lack of sedative effect of low dose sulpiride may be beneficial in maintenance therapy of remitted schizophrenic outpatients. With its relatively low propensity to cause extrapyramidal symptoms and tardive dyskinesia, sulpiride also offers advantages in the treatment of schizophrenic patients who are intolerant of conventional antipsychotics.Pharmacodynamic PropertiesIn contrast to the classical antipsychotic drugs such as haloperidol and chlorpromazine, sulpiride shows selective affinity for the dopamine D2- and D3-receptor subgroups, with little affinity for other brain receptors. Peripheral dopamine receptors in blood vessels and gastrointestinal smooth muscle are also antagonised by sulpiride. Pharmacodynamic properties distinguishing sulpiride as an atypical antipsychotic include lack of inhibition of dopamine-induced stimulation of adenylate cyclase, induction of weak catalepsy, weak antagonism of apomorphine-induced locomotion and lack of inhibition of apomorphine-induced behaviour in animal models. In humans, disinhibitory properties and lack of sedation are noted. As with other dopamine D2-receptor antagonists, sulpiride has a pronounced stimulatory effect on prolactin release from the pituitary gland.Sulpiride has stereoselective properties, andS-sulpiride appears to be the more active of the 2 enantiomers. However, racemic sulpiride is usually used for the treatment of schizophrenia.Pharmacokinetic PropertiesThe low oral bioavailability of sulpiride is probably due to its incomplete absorption from the gastrointestinal tract. Food tends to decrease the gastrointestinal absorption of sulpiride, as do drugs which increase gastric pH. Distribution and elimination follow linear pharmacokinetics. Sulpiride has low lipid solubility and penetrates the cerebrospinal fluid poorly. Very little metabolism occurs and renal clearance is high, resulting in accumulation of sulpiride in patients with renal dysfunction.The relationship between plasma sulpiride concentration and clinical efficacy is equivocal.Therapeutic EfficacyDose-finding studies suggest that sulpiride is partially selective towards the negative symptoms of schizophrenia at low dosages (400 to 1000 mg/day), with more overt activity against positive symptoms being apparent at higher dosages (> 1000 mg/day). The activating or disinhibitory effect ascribed to low dose sulpiride may be offset at higher doses by a possible deactivating effect.The antipsychotic efficacy of sulpiride 400 to 1400 mg/day has been established in a limited number of double-blind placebo-controlled comparisons of ≤ 3 months' duration in patients with chronic schizophrenia. In patients with prominent negative symptoms, sulpiride 400 mg/day improved affective blunting, poverty of speech and socially detrimental behaviour. When used prophylactically in remitted schizophrenic outpatients, sulpiride 100 to 600 mg/day extended the duration of remission and reduced the relapse rate over a 1-year period.In controlled clinical trials of 1 to 4 months' duration, sulpiride ≤ 3200 mg/day (usually ≤ 1200 mg/day) has shown comparable overall antipsychotic activity to bromperidol 7 to 36 mg/day, chlorpromazine 150 to 600 mg/day, haloperidol 3 to 40 mg/day, perphenazine 4 to 48 mg/day, trifluoperazine 15 to 45 mg/day and zuclopenthixol 25 to 150 mg/day in patients with acute or chronic schizophrenia. A moderate to marked improvement in global psychotic morbidity was reported in ≈ 30 to 50% of chronic schizophrenic patients receiving sulpiride in these trials.In hospitalised patients with either acute schizophrenic episodes or chronic schizophrenia, sulpiride 300 to 1200 mg/day tended to produce a greater improvement in global psychotic morbidity than chlorpromazine 150 to 600 mg/day. Although sulpiride was as active as chlorpromazine against positive psychotic symptoms in patients with acute schizophrenic episodes, it proved superior to the latter in ameliorating autistic symptoms. In hospitalised patients with paranoid or hebephrenic schizophrenia, the antipsychotic action of sulpiride 100 to 2300 (mean 1000) mg/day appeared to be more rapid and wider-ranging than that of haloperidol 0.5 to 10.5 (mean 5.0) mg/day, encompassing depressive and anxious as well as hostile-paranoid symptoms. Among patients with chronic schizophrenia and prominent negative symptoms of apathy and anergia, the response rates to sulpiride 300 to 1200 mg/day and perphenazine 12 to 48 mg/day were comparable; sulpiride, however, appeared to have the more rapid onset of action. Among patients with schizophrenic and schizoaffective psychoses, sulpiride 200 to 1800 mg/day was reported to show greater activity than perphenazine 8 to 80 mg/day against symptoms of depression, somatic concerns and psychomotor retardation.TolerabilityExtrapyramidal symptoms, believed to depend on the extent of dopamine D2-receptor occupancy, occurred in 12.8% of 2851 patients receiving sulpiride in 65 clinical studies. Tardive dyskinesia and neuroleptic malignant syndrome have rarely been associated with sulpiride therapy. Endocrine effects have been reported less often than expected from the pharmacodynamic data.Sulpiride has a low toxicity profile on overdose. Caution is advised in patients receiving sulpiride in conjunction with alcohol (ethanol), levodopa, antihypertensive agents or central depressants.Dosage and AdministrationThe dosage of sulpiride is adjusted according to the most prominent psychiatric symptoms in patients with acute or chronic psychosis: 200 to 600 mg/day in patients with predominantly negative symptoms and 800 to 1600 mg/day in those with mainly positive symptoms. Dosage adjustment is required in patients with severe renal failure.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS