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Description

Phenazepam is a benzodiazepine with an anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnestic properties. Its action is mediated by the enhancement of the activity of gamma-aminobutyric acid (GABA).

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. GABA’s functions within the CNS include involvement in sleep induction and in the control of neuronal excitability, epilepsy, anxiety, memory, and hypnosis. Two subtypes of GABA receptors have been identified: A and B. Benzodiazepines interact with GABAA receptors to produce their sedative, hypnotic, anxiolytic, anticonvulsant, and antinociceptive effects. The GABAA receptors within the CNS are composed of different subunits, 4 of which have been described: a, b, g, and d. These subunits combine to form macromolecular complexes, which include a chloride ion channel and regions to which GABA receptor and benzodiazepines bind, as well as binding sites for other substances. The different types of a subunit comprising the GABAA receptor determine its activity. The presence of a g subunit confers benzodiazepine sensitivity and it is the type of a subunit(s) present that determines whether the benzodiazepines activity is mainly anxiolytic or mainly sedative. Two types of benzodiazepine receptor are suggested: type I, found throughout the brain and in large concentrations in the cerebellum and type II found mainly in the cerebral cortex, spinal cord, and hippocampus. It is the benzodiazepine type I receptors that are thought to be responsible for the anxiolytic actions of benzodiazepines. The possibility of different types of GABA receptor associated with different functions remains to be fully exploited with the development of a benzodiazepine specially selected for its anxiolytic effect and lacking sedative and muscle relaxant activity.

Phenazepam is used in the short-term treatment of severe anxiety disorders, as a hypnotic in the short-term management of insomnia, as a sedative and premedicant, as an anticonvulsant (particularly in the management of status epilepticus and febrile convulsions), in the control of muscle spasm, and in the management of withdrawal symptoms.

Phenazepam is administered orally with the risk of dependence very much influencing the dose and duration of treatment. Doses should be the lowest that can control symptoms and courses of treatment should be short, not normally exceeding 4 weeks, with Phenazepam being withdrawn gradually. Elderly and debilitated patients should be given not more than one-half the usual adult dose. Dosage reduction may also be required in patients with liver or kidney dysfunction.

Phenazepam may be given for severe anxiety in oral doses of 0.25 to 0.5 mg 2-3 times daily to a maximum of 10 mg daily (for adults).

Benzodiazepines have a limited role in insomnia and Phenazepam is used for the short-term management of insomnia associated with anxiety in a dose of 0. 25 – 2.5 mg be mouth at bedtime.

Phenazepam is used in a variety of seizures.It is given by mouth as an adjunct in some types of epilepsy; for this purpose, 2 to 10 mg may be given daily in divided doses.

Symptoms of the alcohol withdrawal syndrome may be controlled by Phenazepam given by mouth in a dose of 2.5 to 5 mg daily.

Drowsiness, sedation, muscle weakness, and ataxia are the most frequent adverse effects of Phenazepam use. They generally decrease on continued administration and are a consequence of CNS depression. Less frequent effects include vertigo, headache, confusion, depression, slurred speech or dysarthria, changes in libido, tremor, visual disturbances, urinary retention or incontinence, gastrointestinal disturbances, changes in salivation, and amnesia. Some patients may experience a paradoxical excitation, which may lead to hostility, aggression, and disinhibition. Jaundice, blood disorders, and hypersensitivity reactions have been reported rarely. Raised liver enzyme values have occurred.

Overdosage can produce CNS depression and coma or paradoxical excitation. However, fatalities are rare when taken alone.

Use of Phenazepam in the first trimester of pregnancy has occasionally been associated with congenital malformations in the infant but no clear relationship has been established. Administration of Phenazepam in late pregnancy has been associated with the intoxication of the neonate.

Treatment of adverse effects

The treatment of benzodiazepine overdosage is generally symptomatic and supportive. Activated charcoal may be given to those patients who have taken more than 1 mg per kg body-weight of Phenazepam and who present within 1 hour. Gastric lavage is generally not advocated in overdoses of benzodiazepines alone. The specific benzodiazepine antagonist, flumazenil, is rarely required; if used expert advice is essential since serious adverse effects may occur in patients dependent on benzodiazepines. It should be used with extreme caution, if at all, in multiple drug overdoses or for the differential diagnosis of unclear cases of overdose.

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