DOCSLIB.ORG

Effects of Lormetazepam and of Flurazepam on Sleep

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Effects of Lormetazepam and of Flurazepam on Sleep Br. J. clin. Pharmac. (1984), 17, 531-538 Effects of lormetazepam and of flurazepam on sleep KIRSTINE ADAM & I. OSWALD University Department of Psychiatry. Royal Edinburgh Hospital, Edinburgh EH 10 5HF 1 Nine poor sleepers of mean age 61 years took part in a double-blind, balanced order study in which, during three periods of 3 weeks, each took lormetazepam 1 mg, lormetaze- pam 2.5 mg, and flurazepam 30 mg. 2 Using electrophysiological measures, sleep was found to increase by 0.75 h with each treatment condition, mainly through more of stage 2 sleep. The treatments reduced the delay to sleep and led to fewer and shorter awakenings, with little difference among the three treatments. Slow-wave sleep was reduced by flurazepam and by lormetazepam 2.5 mg. 3 After flurazepam intake ceased, there was evidence of persisting drug effects for as long as 7 nights. In contrast, when lormetazepam 2.5 mg ceased, there was significant rebound reduction of sleep duration below baseline for up to 3 withdrawal nights, and there was a similar though non-significant trend after lormetazepam 1 mg had ceased. 4 Wakefulness in the final 2 h of nocturnal recording during the third week of drug intake was significantly reduced below baseline by flurazepam, but was little affected by lormetazepam. 5 The differences among the treatment conditions could be attributed to the long- persistence of flurazepam vs the more rapid elimination of lormetazepam. Keywords lormetazepam flurazepam sleep Introduction Lormetazepam and flurazepam are benzodia- design included 3 weeks of regular intake, to see zepine derivatives in use as hypnotics, and if tolerance and withdrawal effects could be differing sharply in their persistence in the body. measured. Lormetazepam has an elimination half-life of Seven women (aged 54, 54, 60, 60, 63, 65, 66 about 10 h in young adults, and 20 h in the elderly years) and two men (57, 62 years), mean age 61 (Humpel et al., 1979, 1980). Flurazepam, years, chosen because they considered them- through its principal active metabolite, has an selves to be poor sleepers, and to be of the age elimination half-life of the order of 100 h even in and sex distribution of those who commonly take young adults (Breimer & Jochemsen, 1983). We hypnotic drugs, took part. They had taken no sought to measure and to compare their effects CNS drugs in the preceding months, they were on sleep. asked not to take other drugs or alcohol. The It may be assumed that an hypnotic should study was approved by the Royal Edinburgh increase the time spent asleep, and reduce the Hospital Ethics Committee and each subject amount of wakefulness interrupting sleep, gave informed consent. though it is uncertain to what degree there is a Each subject participated in three sequences, correlation between duration of sleep, its sub- each of 6 weeks, with 4-week intervals between jective quality and its presumptive restorative the first and second and between the second and value (Adam, 1979). Hypnotic drugs are third. Throughout each sequence the subjects commonly taken for weeks or more and so the took matching capsules every night at bedtime 531 532 Kirstine Adam & I. Oswald and during the first 2 weeks these were placebo used, and this was used for sleep latency, capsules, during the next 3 weeks they contained measures of wakefulness and amounts of slow active drug, and in the sixth week placebos again wave sleep. Where analysis of variance proved were taken. During each 3-week period of active significant, correlated t-tests or the Wilcoxon drug, the same preparation was taken each signed-ranks test were used. In the t-tests night, and during one 3-week period the subject degrees of freedom were 8, and in the Wilcoxon took lormetazepam 1 mg, in another 3-week generally 9, depending on the number of non- period the subject took lormetazepam 2.5 mg zero differences. A further analysis of variance and during the other 3-week period the subject was carried out to determine whether there were took flurazepam 30 mg. The order of admin- any differences among the drugs during drug- istration of drug was by a latin square design, taking periods. The data used in these analyses with 'single-blind' conditions for the placebo were the differences from the baseline means. A periods and 'double-blind' conditions for the drug term (df = 2,16) referred to differences active drug periods. Subjects attended the sleep among the three drugs, additionally a night term laboratory on a total of 14 nights during each 6 (df = 1,8), indicated any consistent difference weeks. In the first week of placebos there were 2 between the early and late drug periods nights at the sleep laboratory for adaptation and irrespective of the drug being taken and a drug x in the second week 2 nights for the recording of night interaction term revealed any difference baseline values. The first and fourth nights of the among the treatments in the pattern of change subsequent week gave 'early drug' data. At the between the early and late drug periods. There- end of the fourth week there was a further after, correlated t-tests between pairs of con- adaptation night and in the fifth week (the third ditions were carried out to compare the drugs, week of active drug) the nineteenth and twenty- particularly during the early and late drug first nights on the drug gave 'late drug' data. In periods, using the differences from the baseline the final week the first, second, third, fifth and means. seventh nights provided withdrawal data. To see if the withdrawal of any one of the On all nights the electroencephalogram, eye drugs led to greater disturbance of sleep, further movements and submental muscle tone were analysis of variance was carried out in which recorded. Lights-out was at approximately 22.30 three different withdrawal periods (drug term) at h, and 8 h 45 min was recorded each night. five levels (night term) were compared, using Subjects slept in comfortable, air-conditioned differences from the baseline means. The drug bedrooms. Ultimately the records were coded term could thereby reveal differences among the and scored 'blind' into the different stages of drugs upon withdrawal. The night term could sleep and wakefulness (Rechtschaffen & Kales show if there was a significant change across the 5 1968). Thereafter the code was broken, and the individual nights following withdrawal and the raw data analyzed by a computer programme, drug x night interaction term could reveal any and finally by use of the BMDP statistical inter-dependence. When appropriate, correlated packages of the Health Sciences Computing t-tests were subsequently employed using Facility, University of California. differences from baseline means to compare, for In the statistical analysis, the mean of the 2 example, the effect of withdrawal of flurazepam baseline nights, the mean of the 2 early drug 30 mg with the effect of withdrawal of one of the nights, and the mean of the 2 late drug nights doses of lormetazepam on a specified night. were determined for each individual for each of 33 different sleep measures and these means have been used in the analysis of results, Results together with the individual values for each of In Tables 1, 2 and 3 are summarized the data of the 5 withdrawal nights. In the first place, each of principal interest and we elaborate below the the three drug sequences was treated separately main findings. by an analysis of variance with repeated measures to determine whether any of the Sleep duration increased individual drugs had an effect on the particular measure of sleep. Here the degrees of freedom Subjects slept about 0.75 h longer with any of the were always 7,56. The individual withdrawal three treatments, mainly through increased nights were used rather than the means because duration of stage 2 sleep. Making comparisons mean values could conceal systematic changes with the baseline means for total sleep, and using with time following the withdrawal. Where, for t-tests, for all three treatments the early drug any measure, the co-efficient of variation was mean and the late drug mean were both signifi- consistently above 0.50, the non-parametric cantly lengthened at the P < 0.05 criterion or Friedman's analysis of variance by ranks was better. The same was true when sleep duration Lormetazepam, flurazepam and sleep 533 .t st el*|tf kt^°o N b $zQ 00 0 0 £ b ^ N 0 11o _ o cq en worl W)On 0e 0 0 e 0 1. cq (ON tn en 'ICNo0 n C1* 'I cq}N _ 00x oo 't cn 00 +1N N '+l +l eq +l +l 00 O' 00 a) r- en en 'I - 00 en t,oo00 oio 0; C£c4£ en 25e n " W) tz +l N~~~~~~~ +l " +l X ttoo-^N+l +l O r0 00 0N Nt r1 'I W) cq r-t O 00'I 'I 08t U) tnO 'I r1 N t cq+ +l +l cq +l +l W Q m b -0s 0 sO ^ F t - o O N - CsO e0rIC .Y; ~~~~~en+1 +1 rq +1 +1 m ON Q _ sCM oy~~~-I - oen 'ItU'I CN W) cn ;~~~~~~~~~~~~~~~~t cn °NN+C) un 1£0 t-N = <~~~~~~'~ +l +l rq +l +l = z z o ts xo 'It£ enrl o00 't ON No Y < > l- N N ~~~~~00st-1-01en <2-0 +1 L_ +I +n1o^O.Ot+1 en +1 mt Q~~~~~~~r CZ 00 ON IC't_- 'I It W-'I +l W) q QE CC t v} +l) *e t- -) +l st +l tj Oo +1 +1 'rz X N r a E9 ;2 _ _ _ _ A=tt_* 534 Kirstine Adam & l.
Load more

Recommended publications
  • Uso Adecuado De BZD En Insomnio Y Ansiedad.Pdf
    Vol. 6 Nº 1 · OCTUBRE 2014 BOLETÍN CANARIO DE USO RACIONAL DEL MEDICAMENTO DEL SCS Uso adecuado de BENZODIAZEPINAS en insomnio y ansiedad. SUMARIO PERFIL FARMACOLÓGICO DE LAS BZD (Tabla 1). - INTRODUCCIÓN 1 - PERFIL FARMACOLÓGICO DE LAS BENZODIAZEPINAS 1 No todas las BZD son iguales, ni tienen las mismas indicaciones. - BENZODIAZEPINAS EN EL INSOMNIO 2 Conocer algunos aspectos sobre su perfil farmacológico es esencial para realizar una prescripción adecuada y segura. - BENZODIAZEPINAS EN LA ANSIEDAD 4 - RECOMENDACIONES PARA SUSPENDER 5 Por lo general las BZD se absorben muy bien por vía oral, mientras TRATAMIENTOS CON BZD que la vía intramuscular presenta una absorción lenta e irregular, por - BIBLIOGRAFÍA 7 lo que no suele ser muy recomendada. En situaciones de emergencia (convulsiones) es preferible utilizar la vía endovenosa. INTRODUCCIÓN Inicio de acción y vida media: el inicio de acción es distinto según el principio activo y constituye un criterio fundamental en la selección de Las benzodiazepinas (BZD) son psicofármacos que actúan aumentan- las BZD. Puede ser: de inicio rápido (0,5-1 h), de utilidad en el insomnio do la acción del ácido gammaaminobutírico (GABA), principal neuro- de conciliación y en crisis de ansiedad; de inicio intermedio (1-3 h) o transmisor inhibidor del sistema nervioso central. Tienen indicaciones de inicio lento (> 3 h), preferibles en insomnio de mantenimiento o terapéuticas diversas, y auque su uso más habitual es en el tratamien- despertar precoz y en la ansiedad generalizada. to de la ansiedad e insomnio, también se utilizan en la inducción a la anestesia, en el tratamiento de las crisis comiciales, en el síndrome La vida media de las BZD es otro de los criterios de selección y puede 5 de abstinencia alcohólica, como tratamiento coadyuvante de de dolor ser : corta (< 6 h); intermedia (6-24 h) y larga (> 24 h).
    [Show full text]
  • Early Morning Insomnia, Daytime Anxiety, and Organic Mental Disorder Associated with Triazolam
    Early Morning Insomnia, Daytime Anxiety, and Organic Mental Disorder Associated with Triazolam Tjiauw-Ling Tan, MD, Edward 0. Bixler, PhD, Anthony Kales, MD, Roger J. Cadieux, MD, and Amy L. Goodman, MD Hershey, Pennsylvania A psychiatric syndrome characterized by agita­ Sleep Disorders Clinic. He began taking triazolam tion, paranoid ideation, depersonalization, and de­ at bedtime in a 0.5-mg dose eight months before pression, as well as paresthesias and hyperacusis, his referral. Although the drug was effective ini­ has been attributed to administration of triazolam tially, tolerance developed, causing the patient to (Halcion).1 The occurrence of these reactions led gradually increase the dosage until eventually he to the removal of the drug from the market in the was taking a total of 1.5 mg nightly. Netherlands. Isolated behavioral side effects that The physical examination revealed no contribu­ include amnesia2-4 and hallucinations5 have also tory conditions. However, assessment of the pa­ been reported with administration of triazolam. tient’s mental status revealed that he was extreme­ Rebound insomnia6 and early morning insom­ ly guarded and suspicious and preoccupied with nia,7 both associated with increases in daytime his sleeplessness to the degree that this hypochon­ anxiety,7,8 are withdrawal syndromes known driacal concern had a delusional quality. He also to occur with rapidly eliminated benzodiazepine described two episodes indicating memory impair­ hypnotics such as triazolam. Rebound insomnia ment; both incidents occurred in the late afternoon consists of a marked increase in wakefulness and involved preparing to eat certain foods, which above baseline levels following drug withdrawal.
    [Show full text]
  • Withdrawing Benzodiazepines in Primary Care
    PC\/ICU/ ADTiriC • CNS Drugs 2009,-23(1): 19-34 KtVltW MKIIWLC 1172-7047/I»/O(X)1«119/S4W5/C1 © 2009 Adis Dato Intocmation BV. All rights reserved. Withdrawing Benzodiazepines in Primary Care Malcolm Luder} Andre Tylee^ and ]ohn Donoghue^ 1 Institute of Psychiatry, King's College London, London, England 2 John Moores University, Liverpool, Scotland Contents Abstract ' 19 1. Benzodiazepine Usage 22 2. Interventions 23 2.1 Simple interventions 23 2.2 Piiarmacoiogicai interventions 25 2.3 Psychoiogical Interventions 26 2.4 Meta-Anaiysis ot Various interventions 27 3. Outcomes 28 4. Practicai Issues 29 5. Otiier Medications 30 5.1 Antidepressants 30 5.2 Symptomatic Treatments 30 6. Conciusions 31 Abstract The use of benzodiazepine anxiolytics and hypnotics continues to excite controversy. Views differ from expert to expert and from country to country as to the extent of the problem, or even whether long-term benzodiazepine use actually constitutes a problem. The adverse effects of these drugs have been extensively documented and their effectiveness is being increasingly questioned. Discontinua- tion is usually beneficial as it is followed by improved psychomotor and cognitive functioning, particularly in the elderly. The potential for dependence and addic- tion have also become more apparent. The licensing of SSRIs for anxiety disorders has widened the prescdbers' therapeutic choices (although this group of medications also have their own adverse effects). Melatonin agonists show promise in some forms of insomnia. Accordingly, it is now even more imperative that long-term benzodiazepine users be reviewed with respect to possible discon- tinuation. Strategies for discontinuation start with primary-care practitioners, who are still the main prescdbers.
    [Show full text]
  • Residual Effects of Sleep Medication on Driving Ability
    Sleep Medicine Reviews (2004) 8, 309–325 www.elsevier.com/locate/smrv CLINICAL REVIEW Residual effects of sleep medication on driving ability Joris C. Verster*, Dieuwke S. Veldhuijzen, Edmund R. Volkerts Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, PO Box 80082, 3508 TB, Utrecht, The Netherlands KEYWORDS Summary Most patients using hypnotics are ambulatory and presumably have a job and Zaleplon; Zolpidem; drive a car. Since driving a car is one of the most common but potentially dangerous Zopiclone; daily activities, hypnotics should act rapidly when needed, but daytime sleepiness and Benzodiazepine; other residual effects that may impair performance are unwanted. This review Hypnotics; Insomnia; summarizes the effects of hypnotics on driving ability as determined with the on-the- Driving; Sedation road driving test during normal traffic. Supportive evidence from epidemiological data, and results from driving simulators and closed-road studies are also considered. On-the-road studies revealed that benzodiazepine hypnotics significantly impaired driving ability the morning following bedtime administration. Impairment was sometimes also significant in the afternoon (16–17 h after administration). Similar driving impairment was observed with zopiclone. However, the magnitude of impairment depends on various factors including the half-life and dosage of the drug, and the time after administration. The results from on-the-road driving studies are supported by evidence obtained in driving simulators and laboratory tests. Epidemiological data and on-the-road studies show that tolerance develops to the impairing effects of hypnotics. However, this is a slow process, and impairment may persist. Patients treated with benzodiazepine hypnotics or zopiclone should be cautioned when driving a car.
    [Show full text]
  • 124.210 Schedule IV — Substances Included. 1
    1 CONTROLLED SUBSTANCES, §124.210 124.210 Schedule IV — substances included. 1. Schedule IV shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. 2. Narcotic drugs. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation containing any of the following narcotic drugs, or their salts calculated as the free anhydrous base or alkaloid, in limited quantities as set forth below: a. Not more than one milligram of difenoxin and not less than twenty-five micrograms of atropine sulfate per dosage unit. b. Dextropropoxyphene (alpha-(+)-4-dimethylamino-1,2-diphenyl-3-methyl-2- propionoxybutane). c. 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol, its salts, optical and geometric isomers and salts of these isomers (including tramadol). 3. Depressants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation: a. Alprazolam. b. Barbital. c. Bromazepam. d. Camazepam. e. Carisoprodol. f. Chloral betaine. g. Chloral hydrate. h. Chlordiazepoxide. i. Clobazam. j. Clonazepam. k. Clorazepate. l. Clotiazepam. m. Cloxazolam. n. Delorazepam. o. Diazepam. p. Dichloralphenazone. q. Estazolam. r. Ethchlorvynol. s. Ethinamate. t. Ethyl Loflazepate. u. Fludiazepam. v. Flunitrazepam. w. Flurazepam. x. Halazepam. y. Haloxazolam. z. Ketazolam. aa. Loprazolam. ab. Lorazepam. ac. Lormetazepam. ad. Mebutamate. ae. Medazepam. af. Meprobamate. ag. Methohexital. ah. Methylphenobarbital (mephobarbital).
    [Show full text]
  • S1 Table. List of Medications Analyzed in Present Study Drug
    S1 Table. List of medications analyzed in present study Drug class Drugs Propofol, ketamine, etomidate, Barbiturate (1) (thiopental) Benzodiazepines (28) (midazolam, lorazepam, clonazepam, diazepam, chlordiazepoxide, oxazepam, potassium Sedatives clorazepate, bromazepam, clobazam, alprazolam, pinazepam, (32 drugs) nordazepam, fludiazepam, ethyl loflazepate, etizolam, clotiazepam, tofisopam, flurazepam, flunitrazepam, estazolam, triazolam, lormetazepam, temazepam, brotizolam, quazepam, loprazolam, zopiclone, zolpidem) Fentanyl, alfentanil, sufentanil, remifentanil, morphine, Opioid analgesics hydromorphone, nicomorphine, oxycodone, tramadol, (10 drugs) pethidine Acetaminophen, Non-steroidal anti-inflammatory drugs (36) (celecoxib, polmacoxib, etoricoxib, nimesulide, aceclofenac, acemetacin, amfenac, cinnoxicam, dexibuprofen, diclofenac, emorfazone, Non-opioid analgesics etodolac, fenoprofen, flufenamic acid, flurbiprofen, ibuprofen, (44 drugs) ketoprofen, ketorolac, lornoxicam, loxoprofen, mefenamiate, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, pranoprofen, proglumetacin, sulindac, talniflumate, tenoxicam, tiaprofenic acid, zaltoprofen, morniflumate, pelubiprofen, indomethacin), Anticonvulsants (7) (gabapentin, pregabalin, lamotrigine, levetiracetam, carbamazepine, valproic acid, lacosamide) Vecuronium, rocuronium bromide, cisatracurium, atracurium, Neuromuscular hexafluronium, pipecuronium bromide, doxacurium chloride, blocking agents fazadinium bromide, mivacurium chloride, (12 drugs) pancuronium, gallamine, succinylcholine
    [Show full text]
  • Calculating Equivalent Doses of Oral Benzodiazepines
    Calculating equivalent doses of oral benzodiazepines Background Benzodiazepines are the most commonly used anxiolytics and hypnotics (1). There are major differences in potency between different benzodiazepines and this difference in potency is important when switching from one benzodiazepine to another (2). Benzodiazepines also differ markedly in the speed in which they are metabolised and eliminated. With repeated daily dosing accumulation occurs and high concentrations can build up in the body (mainly in fatty tissues) (2). The degree of sedation that they induce also varies, making it difficult to determine exact equivalents (3). Answer Advice on benzodiazepine conversion NB: Before using Table 1, read the notes below and the Limitations statement at the end of this document. Switching benzodiazepines may be advantageous for a variety of reasons, e.g. to a drug with a different half-life pre-discontinuation (4) or in the event of non-availability of a specific benzodiazepine. With relatively short-acting benzodiazepines such as alprazolam and lorazepam, it is not possible to achieve a smooth decline in blood and tissue concentrations during benzodiazepine withdrawal. These drugs are eliminated fairly rapidly with the result that concentrations fluctuate with peaks and troughs between each dose. It is necessary to take the tablets several times a day and many people experience a "mini-withdrawal", sometimes a craving, between each dose. For people withdrawing from these potent, short-acting drugs it has been advised that they switch to an equivalent dose of a benzodiazepine with a long half life such as diazepam (5). Diazepam is available as 2mg tablets which can be halved to give 1mg doses.
    [Show full text]
  • The Emergence of New Psychoactive Substance (NPS) Benzodiazepines
    Issue: Ir Med J; Vol 112; No. 7; P970 The Emergence of New Psychoactive Substance (NPS) Benzodiazepines. A Survey of their Prevalence in Opioid Substitution Patients using LC-MS S. Mc Namara, S. Stokes, J. Nolan HSE National Drug Treatment Centre Abstract Benzodiazepines have a wide range of clinical uses being among the most commonly prescribed medicines globally. The EU Early Warning System on new psychoactive substances (NPS) has over recent years detected new illicit benzodiazepines in Europe’s drug market1. Additional reference standards were obtained and a multi-residue LC- MS method was developed to test for 31 benzodiazepines or metabolites in urine including some new benzodiazepines which have been classified as New Psychoactive Substances (NPS) which comprise a range of substances, including synthetic cannabinoids, opioids, cathinones and benzodiazepines not covered by international drug controls. 200 urine samples from patients attending the HSE National Drug Treatment Centre (NDTC) who are monitored on a regular basis for drug and alcohol use and which tested positive for benzodiazepine class drugs by immunoassay screening were subjected to confirmatory analysis to determine what Benzodiazepine drugs were present and to see if etizolam or other new benzodiazepines are being used in the addiction population currently. Benzodiazepine prescription and use is common in the addiction population. Of significance we found evidence of consumption of an illicit new psychoactive benzodiazepine, Etizolam. Introduction Benzodiazepines are useful in the short-term treatment of anxiety and insomnia, and in managing alcohol withdrawal. 1 According to the EMCDDA report on the misuse of benzodiazepines among high-risk opioid users in Europe1, benzodiazepines, especially when injected, can prolong the intensity and duration of opioid effects.
    [Show full text]
  • Benzodiazepines Factsheet
    Benzodiazepines This factsheet gives information about benzodiazepine medication. This medication is sometimes used to treat anxiety. Your doctor may prescribe this medication if your anxiety has become severe or if you are very distressed. Benzodiazepines are a type of medication that are used to treat anxiety. You may get side effects from taking this kind of medication. If you get side effects that you are worried about, you should see your doctor. You can become addicted to benzodiazepines. Therefore, you should not take them for longer than one month. You may get withdrawal symptoms when you stop taking benzodiazepines. You should talk to your doctor before you stop taking them. Your doctor may gradually take you off your medication if you have been taking them for a long time. This factsheet covers: 1. What are benzodiazepines? 2. Are there different types of benzodiazepines? 3. Are there any side effects? 4. What if I want to I stop taking benzodiazepines? 5. Do benzodiazepines affect other medication? 6. Does alcohol affect my benzodiazepines? 7. Can I drive when taking benzodiazepines? 8. What else should I consider before taking benzodiazepines? 1 1. What are benzodiazepines? Your doctor may offer you benzodiazepines if you have symptoms of anxiety which are causing you a lot of distress or if you are having difficulty sleeping. Benzodiazepines are a type of sedative and are mostly used as short-term treatment. They work by making the calming chemicals released by your body more powerful. You should not take benzodiazepines for longer than one month. If you take them for longer, you can become tolerant to them (meaning you need more to have the same effect), and you may also become dependent (addicted) to them.
    [Show full text]
  • DBL Flumazenil Data Sheet
    NEW ZEALAND DATA SHEET 1. PRODUCT NAME DBL™ Flumazenil Injection 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Ampoules contain 0.1 mg/mL flumazenil in aqueous solution (for intravenous administration) and also the following ingredients: disodium edetate, acetic acid, sodium chloride, sodium hydroxide in water for injections adjusted to pH 4.0. DBL Flumazenil Injection is available as 0.5 mg/5 mL and 1 mg/10 mL ampoules. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM DBL Flumazenil Injection is a colourless to almost colourless clear liquid, adjusted to pH 4.0. Solution for injection. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications DBL Flumazenil Injection is indicated for use in hospitalised patients for the reversal of acute benzodiazepine effects (overdose or therapeutic). Hospitalised patients are patients admitted to hospital, inpatient care and under continued professional observation while under the influence of flumazenil. Not to be used in outpatients or short stay patients. Not to be used as a diagnostic. 4.2 Dose and method of administration DBL Flumazenil Injection should be administered intravenously by an anaesthetist or experienced physician. Dosage should be titrated for the intended effect. Since the duration of action of some benzodiazepines may exceed that of DBL Flumazenil Injection, repeated doses may be required if sedation recurs following awakening. The use of DBL Flumazenil Injection should be balanced against the risk of precipitating withdrawal symptoms (see section 4.4). The desirability of retaining a degree of sedation in the early postoperative period should be considered. DBL Flumazenil Injection may be diluted in glucose 5% in water or 0.9% NaCl for infusion and may also be used concurrently with other resuscitative procedures.
    [Show full text]
  • Zopiclone Produces Effects on Human Performance Similar to Flurazepam, Lormetazepam and Triazolam
    Br. J. clin. Pharmac. (1986), 21, 647-653 Zopiclone produces effects on human performance similar to flurazepam, lormetazepam and triazolam A. N. GRIFFITHS', D. M. JONES2 & A. RICHENS1 'Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff and 2Department of Applied Psychology, University of Wales Institute of Science and Technology, Cardiff 1 The cognitive function and psychomotor performance of 10 healthy male volunteers were measured following single oral doses of: zopiclone (7.5 mg), flurazepam (15 mg), lormetazepam (1 mg), triazolam (0.25 mg) and placebo. 2 The performance tests selected (stroop task, five choice serial reaction time, memory span, logical reasoning, mood and saccadic eye movement analysis) were thought to reflect aspects of normal daily activity. 3 The tests demonstrated a clear reduction of performance for all active treatments. No drug emerged as the most potent sedative overall, as each of the tests was affected to a different degree by each drug. 4 Drug effects were not qualitatively different between active treatments so that zopi- clone was indistinguishable from the three benzodiazepines with which it was compared. Keywords zopiclone benzodiazepines human performance saccadic eye movements Introduction Zopiclone is a cyclopyrrolone derivative which, (7.5 mg) has been shown to be effective as an although structurally unrelated to the benzodia- hypnotic (Wickstrom & Giercksky, 1980), zepines, shares their pharmacological profile. and furthermore, Lader & Denney (1983) Binding studies have shown that zopiclone binds reported this dose to be the preferred hypnotic to brain benzodiazepine receptors but is not dose. recognised by peripheral (renal) benzodiazepine The marketed benzodiazepines selected for receptors.
    [Show full text]
  • 1601 Gilhooly.Qxd
    Brief reports What happens when doctors stop prescribing temazepam? Use of alternative therapies THOMAS C GILHOOLY was followed up by the research nurse (MW) and invited to take part in a home interview. MARY G O WEBSTER NORMAN W POOLE Results Ninety-one patients were recruited: 46 were allocated to the anti- SUE ROSS histamine/chloral group, 45 to the benzodiazepine group. The characteristics of the study groups were similar at the time of SUMMARY recruitment (Table 1). A similar number of patients in each We investigated the withdrawal of temazepam in a single gen- group were interviewed: 36 (78%) of the antihistamine/chloral eral practice using two alternative prescribing policies: an alter- group, 38 (84%) of the benzodiazepine group. native benzodiazepine; or an alternative group of drugs recom- Of the antihistamine/chloral group, 32 (70%) were initially mended for short-term management of insomnia, including changed to one of the recommended antihistamines; 28 (62%) of sedative antihistamines and chloral hydrate. The study showed the benzodiazepine group were prescribed one of the recommend- that temazepam prescribing in general practice can be reduced ed benzodiazepines. Only eight out of 36 (22%) of the antihista- or stopped by using a simple intervention. An alternative benzo- mine/chloral group interviewed were satisfied with the initial diazepine is useful in helping patients to stop their use of hyp- change, compared with 21 out of 38 (55%) of the benzodiazepine notic agents. The use of antihistamines as substitute hypnotics group (χ2 = 8.47; df = 1; P = 0.004). The antihistamine/chloral is not advocated on the basis of our findings.
    [Show full text]