Flurazepam (marketed under the brand names
Dalmane and
Dalmadorm) is a drug which is a
benzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
derivative. It possesses
anxiolyticAn anxiolytic is a drug used for the treatment of symptoms of anxiety. Anxiolytics have been shown to be useful in the treatment of anxiety disorders, as have antidepressants such as the selective serotonin reuptake inhibitors .Though not anxiolytics, beta-receptor blockers such as propranolol and...
,
anticonvulsantThe 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. The goal of an anticonvulsant is to suppress the rapid and...
,
sedativeA sedative is a substance that induces sedation by reducing irritability or excitement.At higher doses it may result in slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes...
and skeletal muscle relaxant properties. It produces a metabolite with a very long
half-lifeHalf-life is the period of time, for a substance undergoing decay, to decrease by half. The name originally was used to describe a characteristic of unstable atoms , but may apply to any quantity which follows a set-rate decay....
(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 (marketed under the brand names
Dalmane and
Dalmadorm) is a drug which is a
benzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
derivative. It possesses
anxiolyticAn anxiolytic is a drug used for the treatment of symptoms of anxiety. Anxiolytics have been shown to be useful in the treatment of anxiety disorders, as have antidepressants such as the selective serotonin reuptake inhibitors .Though not anxiolytics, beta-receptor blockers such as propranolol and...
,
anticonvulsantThe 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. The goal of an anticonvulsant is to suppress the rapid and...
,
sedativeA sedative is a substance that induces sedation by reducing irritability or excitement.At higher doses it may result in slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes...
and skeletal muscle relaxant properties. It produces a metabolite with a very long
half-lifeHalf-life is the period of time, for a substance undergoing decay, to decrease by half. The name originally was used to describe a characteristic of unstable atoms , but may apply to any quantity which follows a set-rate decay....
(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. Effects start approximately 1/2 to 1 hour after oral administration.
Indications
It is used for short-term treatment of patients with
insomniaInsomnia is a symptom of any of several sleep disorders, characterized by persistent difficulty falling asleep or staying asleep despite the opportunity. Insomnia is a symptom, not a stand-alone diagnosis or a disease. By definition, insomnia is "difficulty initiating or maintaining sleep, or both"...
. 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.
loprazolamLoprazolam 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 1mg tablets...
,
lormetazepamLormetazepam is available as a generic or available under the following trade or brand names and is also sometimes known as methyllorazepam, is a drug which is a benzodiazepine derivative...
,
temazepamTemazepam is an intermediate-acting 3-hydroxy benzodiazepine. It is generally prescribed for the short-term treatment of sleeplessness in patients who have difficulty maintaining sleep. Temazepam is not effective for induction of 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 is a neurological sign and symptom consisting of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of 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.
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 is a drug which is a benzodiazepine derivative which is used to treat anxiety disorders. 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.Fosazepam is of relatively low potency...
, and
nitrazepamNitrazepam 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 effectRebound effect is the tendency of a medication, when discontinued, to cause a return of the symptoms being treated to be more severe than before...
or
benzodiazepine withdrawal syndromeBenzodiazepine 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 reduces the dosage too rapidly...
may occur about four days after discontinuation of medication.
Elderly
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
nonbenzodiazepineThe nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs whose pharmacological actions are similar to those of the benzodiazepines, but are structurally distant or unrelated to the benzodiazepines on a chemical level...
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 amnesiaAnterograde amnesia is a loss of the ability to create memories after the event that caused the amnesia occurs. Anterograde amnesia and retrograde amnesia, where memories created prior to the event are lost, can occur together in the same patient...
), 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 , first marketed as Valium by Hoffmann-La Roche, is a benzodiazepine derivative drug. It possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnestic properties. It is commonly used for treating anxiety, insomnia, seizures, muscle spasms, restless legs...
,
clonazepamClonazepam is a benzodiazepine derivative with highly potent anticonvulsant, muscle relaxant, and anxiolytic properties. It is marketed by Roche under the trade-names Klonopin in the United States, and Ravotril in Chile. Other names like Rivotril or Rivatril are known throughout the large majority...
,
oxazepamOxazepam , is a drug which is a benzodiazepine derivative...
,
lorazepamLorazepam, initially marketed under the brand names Ativan and Temesta, is a benzodiazepine drug with short to medium duration of action. It has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant and muscle relaxant...
,
nitrazepamNitrazepam 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...
,
bromazepamBromazepam is a benzodiazepine derivative drug, developed in the 1970s...
and
clorazepateClorazepate , is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Clorazepate was discontinued in February 2006 in the United Kingdom. Clorazepate is a prodrug for desmethyldiazepam which is rapidly produced as...
. 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
lipophilicLipophilicity, , 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 GABA
A receptor via binding to the benzodiazepine site on the GABA
A receptor causing an increase influx of chloride ions into the GABA
A neuron. Flurazepam is a unique benzodiazepine in that it is a
partial agonistPartial 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 milkHuman breast milk refers to the milk produced by a mother to feed her baby. It provides the primary source of nutrition for newborns before they are able to eat and digest other foods; older infants and toddlers may continue to be breastfed...
.
Drug misuse
Flurazepam is a drug with the potential for misuse. Two types of drug misuse can occur either recreational misuse is 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 SubstancesThe Convention on Psychotropic Substances is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, and psychedelics. During the 1960 such drugs became widely available. Government authorities opposed this for numerous reasons, arguing that along with...
.
http://www.incb.org/pdf/e/list/green.pdf
External links