Flurazepam
Encyclopedia
Flurazepam 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.http://www.non-benzodiazepines.org.uk/equivalents.html Flurazepam is therefore unsuitable as a sleeping medication for some individuals due to next day sedation.
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.
. Flurazepam has abuse potential and should never be used with alcohol or any other substance that can cause drowsiness. Additive 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.
, and nitrazepam
lost some of their effect after seven days administration in psychogeriatric patients. Flurazepam shares cross tolerance with barbiturates and barbiturates can easily be substituted by flurazepam in those who are habituated to barbiturate sedative hypnotics.
After discontinuation of flurazepam a rebound effect
or benzodiazepine withdrawal syndrome
may occur about four days after discontinuation of medication.
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. 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.)
, clonazepam
, oxazepam
, lorazepam
, nitrazepam
, bromazepam
and clorazepate
. Flurazepam generates an active metabolite with a very long elimination half-life of 40–250 hours. 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.
Flurazepam is lipophilic
, is metabolised 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. Flurazepam is a unique benzodiazepine in that it is a partial agonist
of benzodiazepine receptors whereas other benzodiazepines are full agonists of benzodiazepine receptors.
Flurazepam is contraindicated in pregnancy. It is recommended to withdraw flurazepam during breast feeding, as flurazepam is excreted in breast milk
.
.http://www.incb.org/pdf/e/list/green.pdf
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
derivative. It possesses anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
, anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
, sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
and skeletal muscle relaxant properties. It produces a metabolite with a very long half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
(40–250 hours), which may stay in the bloodstream for up to four days.http://www.non-benzodiazepines.org.uk/equivalents.html Flurazepam is therefore unsuitable as a sleeping medication for some individuals due to next day sedation.
Indications
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
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
Loprazolam
Loprazolam marketed under the brand names Dormonoct, Havlane, Sonin, Somnovit, is a drug which is an imidazole benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It is available in 1 mg tablets...
, lormetazepam
Lormetazepam
Lormetazepam Lormetazepam Lormetazepam (INN, or methyl-lorazepam, is a drug which is a short to intermediate acting 3-hydroxy benzodiazepine derivative. It possesses hypnotic, anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties....
, temazepam
Temazepam
Temazepam is an intermediate-acting 3-hydroxy benzodiazepine. It is mostly prescribed for the short-term treatment of sleeplessness in patients who have difficulty maintaining sleep...
). Hypnotics should only be used on a short term basis or in those with chronic insomnia on an occasional basis.
Side effects
The most common adverse effects are dizziness, drowsiness, lightheadedness, and ataxiaAtaxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
. Flurazepam has abuse potential and should never be used with alcohol or any other substance that can cause drowsiness. Additive 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 problems
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. Flurazepam and other benzodiazepines such as fosazepamFosazepam
Fosazepam is a drug which is a benzodiazepine derivative; it is a water soluble salt of diazepam. It has sedative and anxiolytic effects, and is a derivative of diazepam which has been substituted with a dimethylphosphoryl group to improve solubility in water....
, and nitrazepam
Nitrazepam
Nitrazepam is a type of benzodiazepine drug and is marketed in English-speaking countries under the following brand names: Alodorm, Arem, Insoma, Mogadon, Nitrados, Nitrazadon, Ormodon, Paxadorm, Remnos, and Somnite...
lost some of their effect after seven days administration in psychogeriatric patients. Flurazepam shares cross tolerance with barbiturates and barbiturates can easily be substituted by flurazepam in those who are habituated to barbiturate sedative hypnotics.
After discontinuation of flurazepam a rebound effect
Rebound effect
The rebound effect, or rebound phenomenon, is the tendency of some medications, when discontinued suddenly, to cause a return of the symptoms it relieved, and that, to a degree stronger than they were before treatment first began...
or benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms which appear when a person who has taken benzodiazepines long term and has developed benzodiazepine dependence stops taking benzodiazepine drug or during dosage reductions...
may occur about four days after discontinuation of medication.
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.Elderly
Flurazepam, similar to other benzodiazepines and nonbenzodiazepineNonbenzodiazepine
The nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs pharmacologically resembling the benzodiazepines, with similar benefits, side effects and risks, despite having dissimilar or entirely different chemical structures.-Classes:There are currently three...
hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
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. 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
Nonbenzodiazepine
The nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs pharmacologically resembling the benzodiazepines, with similar benefits, side effects and risks, despite having dissimilar or entirely different chemical structures.-Classes:There are currently three...
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
Anterograde amnesia
Anterograde amnesia is a loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. This is in contrast to retrograde amnesia, where memories...
), 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.)
Pharmacology
Flurazepam is a "classical" benzodiazepine, other classical benzodiazepines include; diazepamDiazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
, clonazepam
Clonazepam
Clonazepamis a benzodiazepine drug having anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. It is marketed by Roche under the trade name Klonopin in the United States and Rivotril in Australia, Brazil, Canada and Europe...
, oxazepam
Oxazepam
Oxazepam , is a drug which is a short to intermediate acting 3-hydroxy benzodiazepine derivative...
, lorazepam
Lorazepam
Lorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...
, nitrazepam
Nitrazepam
Nitrazepam is a type of benzodiazepine drug and is marketed in English-speaking countries under the following brand names: Alodorm, Arem, Insoma, Mogadon, Nitrados, Nitrazadon, Ormodon, Paxadorm, Remnos, and Somnite...
, bromazepam
Bromazepam
Bromazepam is a benzodiazepine derivative drug, patented by Roche in the 1963 and developed clinically in the 1970s...
and clorazepate
Clorazepate
Clorazepate , also known as clorazepate dipotassium, is a drug that is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative, hypnotic and skeletal muscle relaxant properties. Clorazepate is a prodrug for desmethyldiazepam, which is rapidly produced as an active metabolite...
. Flurazepam generates an active metabolite with a very long elimination half-life of 40–250 hours. 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.
Flurazepam is lipophilic
Lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...
, is metabolised 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. Flurazepam is a unique benzodiazepine in that it is a partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
of benzodiazepine receptors whereas other benzodiazepines are full agonists of benzodiazepine receptors.
Flurazepam is contraindicated in pregnancy. It is recommended to withdraw flurazepam during breast feeding, as flurazepam is excreted in breast milk
Breast milk
Breast milk, more specifically human milk, is the milk produced by the breasts of a human female for her infant offspring...
.
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.Legal status
Flurazepam is a Schedule IV drug under the Convention on Psychotropic SubstancesConvention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...
.http://www.incb.org/pdf/e/list/green.pdf