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Flurazepam chemical structure
| CAS number |
| ATC code |
| PubChem |
| DrugBank |
|Molecular weight||387.88 g/mol|
|Elimination half-life||40–250 hours|
|Routes of administration||Oral|
Flurazepam (marketed under the brand names Dalmane and Dalmadorm) is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties.
It has the longest half-life of all of the benzodiazepines (40-250 hours), and may stay in the bloodstream for up to four days. Flurazepam is therefore unsuitable as a sleeping medication for some individuals due to next day sedation. However, some individuals benefit from next-day sedation in that they do not require an anxiolytic due to flurazepam therapy.
It is used for short-term treatment of patients with insomnia. Insomnia can be described as a difficulty falling asleep, frequent awakening, early awakenings or a combination of each. Flurazepam is a long acting benzodiazepine and is sometimes used in patients who have difficulty in maintaining sleep. Intermediate half life benzodiazepines are also useful for patients with difficulty in maintaining sleep eg loprazolam, lormetazepam, temazepam. Hypnotics should only be used on a short term basis or in those with chronic insomnia on an occasional basis.
The most common adverse effects are dizziness, drowsiness, lightheadedness and ataxia. Flurazepam has abuse potential and should never be used with alcohol or any other substance that can cause drowsiness. Addictive and possibly fatal results may occur. Flurazepam users should only take this drug strictly as prescribed, and should only be taken directly before the user plans on sleeping a full night. Next day drowsiness is common.
Flurazepam has a very long elimination half life of 40-250 hours, which means the effects of Flurazepam after nighttime administration persist throughout the next day. Residual 'hangover' effects after nighttime administration of flurazepam, such as sleepiness, impaired psychomotor and cognitive functions, may persist into the next day, which may impair the ability of users to drive safely and increase risks of falls and hip fractures.
There is preferential storage of flurazepam in some organs including the heart. Absorption by any administered route and the risk of accumulation is significantly increased in the neonate, and there is clinical justification to recommend the withdrawal of flurazepam during pregnancy and breast feeding, as flurazepam is excreted in breast milk.
A hangover-like effect occurs with flurazepam with impairment of mental arithmetic abilities. After discontinuation of flurazepam a rebound effect may occur about four days after discontinuation of medication. (See benzodiazepine withdrawal syndrome)
Tolerance, dependence and withdrawal problemsEdit
The Committee on the Review of Medicines
The Committee on the Review of Medicines (UK) carried out a review into benzodiazepines due to significant concerns of tolerance, drug dependence and benzodiazepine withdrawal problems and other adverse effects. The committee found that benzodiazepines do not have any antidepressant or analgesic properties and are therefore unsuitable treatments for conditions such as depression, tension headaches and dysmenorrhoea. Benzodiazepines are also not beneficial in the treatment of psychosis due to a lack of efficacy. The committee also recommended against benzodiazepines being used in the treatment of anxiety or insomnia in children. The committee was in agreement with the Institute of Medicine (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the National Institute on Drug Abuse (USA) that there was little evidence that long term use of benzodiazepine hypnotics were beneficial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tended to lose their sleep promoting properties within 3 - 14 days of continuous use and in the treatment of anxiety the committee found that there was little convincing evidence that benzodiazepines retained efficacy in the treatment of anxiety after 4 months continuous use due to the development of tolerance. The committee found that the regular use of benzodiazepines caused the development of dependence characterised by tolerance to the therapeutic effects of benzodiazepines and the development of the benzodiazepine withdrawal syndrome including symptoms such as anxiety, apprehension, tremor, insomnia, nausea, and vomiting upon cessation of benzodiazepine use. Withdrawal symptoms tended to develop within 24 hours on the cessation of a short acting benzodiazepine and within 3 - 10 days after the cessation of a more short acting benzodiazepine. Withdrawal effects could occur after treatment lasting only 2 weeks at therapeutic dose levels however withdrawal effects tended to occur with habitual use beyond 2 weeks and were more likely the higher the dose. The withdrawal symptoms may appear to be similar to the original condition. The committee recommended that all benzodiazepine treatment be withdrawn gradually and recommended that benzodiazepine treatment be used only in carefully selected patients and that therapy be limited to short term use only. It was noted in the review that alcohol can potentiate the central nervous system depressant effects of benzodiazepines and should be avoided. The central nervous system depressant effects of benzodiazepines may make driving or operating machinery dangerous and the elderly are more prone to these adverse effects. In the neonate high single doses or repeated low doses have been reported to produce hypotonia, poor sucking, and hypothermia in the neonate and irregularities in the fetal heart. Benzodiazepines should be avoided in lactation. Withdrawal from benzodiazepines should be gradual as abrupt withdrawal from high doses of benzodiazepines may cause confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal from lower doses may cause depression, nervousness, rebound insomnia, irritability, sweating, and diarrhoea.
- ↑ Rickels K. (1986). The clinical use of hypnotics: indications for use and the need for a variety of hypnotics.. Acta Psychiatr Scand Suppl. 332: 132-41.
- ↑ Vermeeren A. (2004). Residual effects of hypnotics: epidemiology and clinical implications.. CNS Drugs. 18 (5): 297-328.
- ↑ Oelschläger H. (4). [Chemical and pharmacologic aspects of benzodiazepines]. Schweiz Rundsch Med Prax. 78 (27-28): 766-72.
- ↑ Rooke KC. (1976). The use of flurazepam (dalmane) as a substitute for barbiturates and methaqualone/diphenhydramine (mandrax) in general practice.. J Int Med Res. 4 (5): 355-9.
- ↑ Olive G, Dreux C. (Jan 1977). Pharmacologic bases of use of benzodiazepines in peréinatal medicine.. Arch Fr Pediatr. 34(1): 74-89.
- ↑ Hindmarch I. (Nov 1977). A repeated dose comparison of three benzodiazepine derivative (nitrazepam, flurazepam and flunitrazepam) on subjective appraisals of sleep and measures of psychomotor performance the morning following night-time medication.. Acta Psychiatr Scand. 56 (5): 373-81.
- ↑ Viukari M, Linnoila M, Aalto U. (Jan 1978). Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients.. Acta Psychiatr Scand. 57 (1): 27-35.
- ↑ Committee on the Review of Medicines (29). Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines.. Br Med J. 280 (6218): 910-2.
Benzodiazepines (N05BA, N05CD)
Bromazepam • Camazepam • Carburazepam • Chlordiazepoxide • Cinolazepam • Clonazepam • Clorazepate • Cyprazepam • Delorazepam • Demoxepam • Diazepam • Doxefazepam • Elfazepam • Ethyl carfluzepate • Ethyl dirazepate • Ethyl loflazepate • Fletazepam • Fludiazepam • Flunitrazepam • Flurazepam • Flutemazepam • Flutoprazepam • Fosazepam • Gidazepam • Halazepam • Iclazepam • Lopirazepam • Lorazepam • Lormetazepam • Meclonazepam • Medazepam • Menitrazepam • Metaclazepam • Motrazepam • Nimetazepam • Nitrazepam • Nitrazepate • Nordazepam • Nortetrazepam • Oxazepam • Phenazepam • Pinazepam • Pivoxazepam • Prazepam • Proflazepam • Quazepam • QH-II-66 • Reclazepam • Sulazepam • Temazepam • Tetrazepam • Tolufazepam • Tuclazepam • Uldazepam