Flurazepam

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Flurazepam
Flurazepam.svg
Flurazepam3d.png
Systematic (IUPAC) name
7-Chloro-1-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one
Clinical data
Trade names Dalmane
AHFS/Drugs.com monograph
MedlinePlus a682051
Pregnancy
category
  • X (Contraindicated in pregnancy)
Legal status
Routes of
administration		 Oral
Pharmacokinetic data
Bioavailability 83%
Metabolism Hepatic
Biological half-life 40–250 hours
Excretion Renal
Identifiers
CAS Number 17617-23-1 YesY
ATC code N05CD01 (WHO)
PubChem CID: 3393
IUPHAR/BPS 7188
DrugBank DB00690 YesY
ChemSpider 3276 YesY
UNII IHP475989U YesY
KEGG D00329 YesY
ChEMBL CHEMBL968 YesY
PDB ligand ID FL7 (PDBe, RCSB PDB)
Chemical data
Formula C21H23ClFN3O
Molecular mass 387.88 g/mol
  • FC1=CC=CC=C1C2=NCC(N(CCN(CC)CC)C3=C2C=C(C=C3)Cl)=O
  • InChI=1S/C21H23ClFN3O/c1-3-25(4-2)11-12-26-19-10-9-15(22)13-17(19)21(24-14-20(26)27)16-7-5-6-8-18(16)23/h5-10,13H,3-4,11-12,14H2,1-2H3 YesY
  • Key:SAADBVWGJQAEFS-UHFFFAOYSA-N YesY
Physical data
Melting point 79.5 °C (175.1 °F)
  (verify)

Flurazepam[1] (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 produces a metabolite with a very long half-life (40–250 hours), which may stay in the bloodstream for up to four days.[2][unreliable source?] Flurazepam is therefore unsuitable as a sleeping medication for some individuals due to next-day sedation; however, this same effect may also provide next-day anxiety relief. For this reason it is sometimes utilized to treat anxiety-induced insomnia on the night before dental visits and other medical procedures, patients are usually instructed to have someone to drive them to and from the appointment when using flurazepam in this context.

Flurazepam was initially patented in 1963 and went on sale in the United States in 1970.[3]

Medical uses

Dalmane15mg.jpg

Flurazepam is officially indicated for mild to moderate insomnia and as such it is used for short-term treatment of patients with mild to moderate insomnia such as 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 (e.g. loprazolam, lormetazepam, temazepam). Hypnotics should only be used on a short term basis or in those with chronic insomnia on an occasional basis.[4]

Side effects

The most common adverse effects are dizziness, drowsiness, light-headedness, and ataxia. Flurazepam has abuse potential and should never be used with alcoholic beverages 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 and may increase during the initial phase of treatment as accumulation occurs until steady-state plasma levels are attained.

Tolerance, dependence and withdrawal

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Main article: Benzodiazepine withdrawal syndrome

A review paper found that long term use of flurazepam is associated with drug tolerance, drug dependence, rebound insomnia and CNS related adverse effects. Flurazepam is best used for a short time period and at the lowest possible dose to avoid complications associated with long term use. Non-pharmacological treatment options however, were found to have sustained improvements in sleep quality.[5] Flurazepam and other benzodiazepines such as fosazepam, and nitrazepam lost some of their effect after seven days administration in psychogeriatric patients.[6] Flurazepam shares cross tolerance with barbiturates and barbiturates can easily be substituted by flurazepam in those who are habituated to barbiturate sedative hypnotics.[7]

After discontinuation of flurazepam a rebound effect or benzodiazepine withdrawal syndrome may occur about four days after discontinuation of medication.[8]

Contraindications and special caution

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.[9]

Elderly

Flurazepam, similar to other benzodiazepines and nonbenzodiazepine hypnotic drugs causes impairments in body balance and standing steadiness in individuals who wake up at night or the next morning. Falls and hip fractures are frequently reported. The combination with alcohol increases these impairments. Partial, but incomplete tolerance develops to these impairments.[10] An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including flurazepam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy in elderly persons. Tolerability in elderly patients, however, is improved marginally in that benzodiazepines have moderately higher risks of falls, memory problems, and disinhibition ("Paradoxical agitation") when compared to non-benzodiazepine sedatives. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Chronic use of sedative-hypnotic drugs for the management of insomnia does not have an evidence base and has been discouraged due to concerns including potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of sedative hypnotics has been determined to be no better than placebo after 3 months of therapy and worse than placebo after 6 months of therapy. (NEJM, 1983, 1994, et seq.)[11]

Pharmacology

Flurazepam is a "classical" benzodiazepine; some other classical benzodiazepines include diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, bromazepam, and clorazepate.[12] Flurazepam generates an active metabolite with a very long elimination half-life of 40–250 hours.[2][unreliable source?] 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.[13]

Flurazepam is lipophilic, is metabolized hepatically via oxidative pathways. The main pharmacological effect of flurazepam is to increase the effect of GABA at the GABAA receptor via binding to the benzodiazepine site on the GABAA receptor causing an increase influx of chloride ions into the GABAA neuron.[14][15] Flurazepam is a unique benzodiazepine in that it is a partial agonist of benzodiazepine receptors whereas other benzodiazepines are full agonists of benzodiazepine receptors.[16]

Flurazepam is contraindicated in pregnancy. It is recommended to withdraw flurazepam during breast feeding, as flurazepam is excreted in breast milk.[17]

Society and culture

Drug misuse

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See also: Benzodiazepine drug misuse

Flurazepam is a drug with potential for misuse. Two types of drug misuse can occur, either recreational misuse where the drug is taken to achieve a high, or when the drug is continued long term against medical advice.[18]

Legal status

Flurazepam is a Schedule IV drug under the Convention on Psychotropic Substances.[19]

See also

References

  1. ↑ BE 629005 
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External links

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