ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1986.tb08972.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1986.tb08973.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1986.tb08974.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

ABSTRACTIn order to avoid after‐effects during the day, slowly eliminated hypnotic agents should not be used in the treatment of sleep disorders. It has become customary to separate long‐acting from short‐acting benzodiazepines and to use the (terminal) half‐life as the principle of classification. This approach is only justified, however, in the case of quickly absorbed benzodiazepines that have no pharmacologically active metabolites and that exhibit one‐compartment disposition kinetics. In contrast, the duration of action of benzodiazepines characterized by marked two‐compartment disposition kinetics can only be estimated correctly when the potency and all relevant kinetic parameters of the drug preparation and its pharmacologically active metabolites are

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1986.tb08975.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

ABSTRACTWhen the various benzodiazepine hypnotics are studied, large differences are seen with regard to their pharmacokinetic properties and metabolism in man. Some are eliminated from the body at a relatively slow rate (e.g. nitrazepam), others are metabolized rather rapidly (temazepam, triazolam). Some benzodiazepine hypnotics have major active metabolites that are slowly eliminated (flurazepam, quazepam), while others have non‐active metabolites (temazepam, lormetazepam). In hypnotic treatment, the duration of drug action should be restricted to the duration of the night, hence a compound with a relatively short elimination half‐life may represent a more rational choice.An overview is given of the pharmacokinetics of the currently available benzodiazepine hypnotics with emphasis on temazepam and other hydroxylated benzodiazepi

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1986.tb08976.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

ABSTRACTBenzodiazepines are the drugs of choice when initiating hypnotic therapy. Though the mechanism of benzodiazepine action in the central nervous system is similar for all drugs in this class, differences in absorption and pathway of elimination are associated with differences in observed clinical effect. After single‐dose administration, onset of hypnotic effect is most closely related to rate of drug absorption and duration of effect is more closely associated with extent of drug distribution. Relative affinity of the individual benzodiazepine for the specific central nervous system binding site may also determine duration of action. During multiple‐dose chronic therapy, route of metabolic biotransformation and elimination half‐life assume more importance. An increased incidence of adverse drug effects due to high doses of accumulating benzodiazepines may be seen in the elderly and patients with central nervous system deficits or chronic liver disease. Benzodiazepine metabolic biotransformation and clearance is broken into three groups. Group 1—oxidative biotransformation; Group 2—high clearance drugs; Group 3—drug conjugation. Groups 1 and 2 are implicated in a number of drug‐disease and drug‐drug interactions. Group 3 drugs have little change in patients with liver disease or when administered with inhibitors of drug biotransformation. Clinical implications of these metabolic interactions are variable, but inhibition of Group 1 and 2 benzodiazepine clearance has been associated with increased sedation and psychom

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1986.tb08977.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1986.tb08978.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

ABSTRACTThere are three fundamental principles for understanding sleep; (1) the sleeping brain is not a resting brain, (2) the sleeping brain functions in a different manner from the waking brain and (3) the activity and work of the sleeping brain are purposeful. The sleeping brain does fail and this failure is mainfest in a variety of clinical symptoms; all sleep complaints should be taken seriously and investigated. Transient insomnia is uniformly associated with objective sleep disturbances which have been documented following phase shifts of the major sleep period such as that caused by transmeridian travel. However, the degree to which the individual responds to these factors is variable. There is a consensus that sleep medications are indicated for transient and short‐term insomnia. Benzodiazepine hypnotics are commonly used to induce and maintain sleep, and improve daytime alertnes

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1986.tb08979.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

ABSTRACTResidual sedative effects seem to be intrinsic properties of effective hypnotic agents. Residual effects are dose related and more likely if the elimination half‐life is greater than 12 hours. In two separate studies, investigations into effects on performance were carried out using a series of psychometric tests. In the first, a group of skilled radar operators working a shift system were given a pre‐sleep administration of temazepam 20 mg and measurements were made of any residual effects. In the second clinical study, general practice patients suffering from idiopathic insomnia were randomized onto either temazepam 20 mg, triazolam 0.25 mg, nitrazepam 5 mg, flurazepam 15 mg, or placebo. Assessments were made using the Leeds Psychomotor Tester to measure Choice Reaction Time and Critical Flicker Fusion. In a separate test, digit substitution was used to measure sensory processing ability. In addition, the Leeds Sleep Evaluation Questionnaire was completed by each patient in the clinical study to provide a subjective evaluation of ease of getting to sleep, ease of awakening and behaviour after awakening. Neither study showed a residual activity that was likely to impair performance following temazepam 20 mg indicating the usefulness of this drug in the management of idiopathic insomnia and sleep difficulties introduced by changes in scheduling of sleep, i.e. intercontinental travel or shift w

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1986.tb08980.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

ABSTRACTAn hypnotic should be used only when there is evidence of sleep disturbance. The wide range of sleep disorders (e.g. delayed sleep onset or problems of sleep maintenance) and the added complication that the patient may be involved subsequently in skilled work demand that the pharmacokinetics of various hypnotics must be understood before the correct hypnotic can be chosen. Impaired performance is more severe and persists far longer with compounds that are slowly eliminated and with the use of higher doses. The particular situations of aircrew and mountaineers have been studied in detail. Caution must be exercised in the management of aircrew coping with irregularity of rest and work. Temazepam has been used for aircrew for over 10 years and the absence of adverse effects ensures that it remains the recommended hypnotic in this area of medical practice. The relationship of insomnia with the hypoxic environment is undetermined. To investigate this, sleep was studied in six individuals during an expedition to the Himalayas. At altitude, temazepam led to less wakefulness and to drowsy sleep ‐ there were no prolonged sleep latencie

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1986.tb08981.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY