Etizolam
Encyclopedia
Etizolam is a thienodiazepine drug which is a benzodiazepine
analog. The etizolam molecule differs from most other benzodiazepines in that the benzene ring has been replaced by a thiophene
ring. It possesses amnesic, anxiolytic
, anticonvulsant
, hypnotic
, sedative
and skeletal muscle relaxant properties.
A 1mg dose of etizolam is approximately equivalent to that of 10mg of diazepam
, see List of benzodiazepines.
Very Rare
, including rebound insomnia. A neuroleptic malignant syndrome
, a rare event in benzodiazepine withdrawal has been documented in a case of abrupt withdrawal from etizolam.
alpha-hydroxyetizolam which has the same potency as etizolam is eliminated more slowly with a mean half life of just over 8 hours. So it can be classified as a short-medium action benzodiazepine
. Etizolam possesses potent hypnotic
properties. Etizolam acts as a full agonist at the benzodiazepine receptor to produce its range of therapeutic as well as adverse effects. Similar to other benzodiazepines etizolam binds unselectively to benzodiazepine receptor subtypes.
In addition etizolam unlike most other benzodiazepines (some of which can increase levels of estradiol) has prolactogenic effects leading to an increase in prolactin
blood levels.
According to the Italian P.I. sheet etizolam belongs to a new class of diazepine
s, thienotriazolodiazepines. This new class is easily oxidized, rapidly metabolized
, and has a lower risk of accumulation, even after prolonged treatment. Etizolam has an anxiolytic
action about 6 times greater than that of diazepam
. Etizolam produces, especially at higher dosages, a reduction in time taken to fall asleep, an increase in total sleep time and a reduction in the number of awakenings. During tests there were not substantial changes in deep sleep
. There is a reduction of REM sleep. In EEG
tests of healthy volunteers Etizolam showed some characteristics of tricyclic antidepressant
s.
and fluvoxamine
slow down the rate of elimination of etizolam leading to accumulation of etizolam and thus increased pharmacological effects. Carbamazepine
speeds up the metabolism of etizolam resulting in reduced pharmacological effects of etizolam.
. An overdose of etizolam can prove fatal. Although etizolam has a lower LD50 than certain benzodiazepines, the LD50 is still far beyond the prescribed or recommended dose. Many lethal etizolam overdoses were due to drug interactions.
studies.
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
analog. The etizolam molecule differs from most other benzodiazepines in that the benzene ring has been replaced by a thiophene
Thiophene
Thiophene is a heterocyclic compound with the formula C4H4S. Consisting of a flat five-membered ring, it is aromatic as indicated by its extensive substitution reactions. Related to thiophene are benzothiophene and dibenzothiophene, containing the thiophene ring fused with one and two benzene...
ring. It possesses amnesic, 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...
, 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...
, sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
and skeletal muscle relaxant properties.
Indications
- Short-term treatment of insomniaInsomniaInsomnia 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:...
- Short-term treatment of anxietyAnxietyAnxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
or panic attackPanic attackPanic attacks are periods of intense fear or apprehension that are of sudden onset and of relatively brief duration. Panic attacks usually begin abruptly, reach a peak within 10 minutes, and subside over the next several hours...
s, if a benzodiazepine is required
Dosage
- For anxiety: 0.50-1 mg two or three times per day (maximum 2 mg per day)
- For insomnia: 1-2 mg before bedtime
A 1mg dose of etizolam is approximately equivalent to that of 10mg of diazepam
Diazepam
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,...
, see List of benzodiazepines.
Side effects
- BlepharospasmBlepharospasmA blepharospasm , is any abnormal contraction or twitch of the eyelid....
s with long term use
Very Rare
- Erythema annulare centrifugumErythema annulare centrifugumErythema annulare centrifugum is a descriptive term for a skin lesion. The lesions form consists of redness in a ring form that spreads from the center . EAC was first described by Darier in 1916...
skin lesions
Tolerance, dependence and withdrawal
Abrupt or over rapid withdrawal from etizolam as with other benzodiazepines may result in the appearance of the benzodiazepine withdrawal syndromeBenzodiazepine 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...
, including rebound insomnia. A neuroleptic malignant syndrome
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...
, a rare event in benzodiazepine withdrawal has been documented in a case of abrupt withdrawal from etizolam.
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.Pharmacology
Etizolam a thienodiazepine benzodiazepine derivative, is absorbed fairly rapidly with peak plasma levels achieved between 30 minutes and 2 hours and has a mean elimination half life of about 3 and a half hours. However, its pharmacologically active metaboliteActive metabolite
- Prodrugs :Sometimes drugs are formulated deliberately so they will break down inside the body to form the active drug, these are called prodrugs. The reason for this may be because the drug is more stable during manufacture and storage as the prodrug form, or because the prodrug is better...
alpha-hydroxyetizolam which has the same potency as etizolam is eliminated more slowly with a mean half life of just over 8 hours. So it can be classified as a short-medium action benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
. Etizolam possesses potent 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...
properties. Etizolam acts as a full agonist at the benzodiazepine receptor to produce its range of therapeutic as well as adverse effects. Similar to other benzodiazepines etizolam binds unselectively to benzodiazepine receptor subtypes.
In addition etizolam unlike most other benzodiazepines (some of which can increase levels of estradiol) has prolactogenic effects leading to an increase in prolactin
Prolactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
blood levels.
According to the Italian P.I. sheet etizolam belongs to a new class of diazepine
Diazepine
1,2-Diazepine is a seven-membered heterocyclic compound with two nitrogen atoms and three double bonds.-External links:*...
s, thienotriazolodiazepines. This new class is easily oxidized, rapidly metabolized
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
, and has a lower risk of accumulation, even after prolonged treatment. Etizolam has an anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
action about 6 times greater than that of diazepam
Diazepam
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,...
. Etizolam produces, especially at higher dosages, a reduction in time taken to fall asleep, an increase in total sleep time and a reduction in the number of awakenings. During tests there were not substantial changes in deep sleep
Slow-wave sleep
Slow-wave sleep , often referred to as deep sleep, consists of stages 3 and 4 of non-rapid eye movement sleep, according to the Rechtschaffen & Kales standard of 1968. As of 2008, the American Academy of Sleep Medicine has discontinued the use of stage 4, such that the previous stages 3 and 4 now...
. There is a reduction of REM sleep. In EEG
Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...
tests of healthy volunteers Etizolam showed some characteristics of tricyclic antidepressant
Tricyclic antidepressant
Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
s.
Interactions
ItraconazoleItraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...
and fluvoxamine
Fluvoxamine
Fluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor . Fluvoxamine was first approved by the U.S. Food and Drug Administration in 1993 for the treatment of obsessive compulsive disorder . Fluvoxamine CR is approved to treat social anxiety disorder...
slow down the rate of elimination of etizolam leading to accumulation of etizolam and thus increased pharmacological effects. Carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
speeds up the metabolism of etizolam resulting in reduced pharmacological effects of etizolam.
Overdose
Etizolam has been used in cases of suicidal benzodiazepine overdoseBenzodiazepine overdose
Benzodiazepine overdose describes the ingestion of one of the drugs in the benzodiazepine class in quantities greater than are recommended or generally practiced. Death as a result of benzodiazepines is uncommon but does occasionally happen. Deaths after hospital admission are considered to be low...
. An overdose of etizolam can prove fatal. Although etizolam has a lower LD50 than certain benzodiazepines, the LD50 is still far beyond the prescribed or recommended dose. Many lethal etizolam overdoses were due to drug interactions.
Abuse
Etizolam is a drug of potential abuse. Etizolam has been shown to be able to substitute for the behavioural effects of barbiturates in primatePrimate
A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...
studies.
See also
- BrotizolamBrotizolamBrotizolam is a sedative-hypnotic thienodiazepine drug which is a benzodiazepine analog. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties, and is considered to be similar in effect to short-acting benzodiazepines such as triazolam...
- ClotiazepamClotiazepamClotiazepam is a thienodiazepine drug which is a benzodiazepine analog. The clotiazepam molecule differs from most other benzodiazepines in that the benzene ring has been replaced by a thiophene ring...
- BenzodiazepineBenzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
- Benzodiazepine dependenceBenzodiazepine dependenceBenzodiazepine dependence or benzodiazepine addiction is a condition during which a person is dependent on benzodiazepine drugs. Dependence can be either a psychological dependence, physical dependence, or a combination of the two...
- Benzodiazepine withdrawal syndromeBenzodiazepine 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 during dosage reductions...
- Long-term effects of benzodiazepines