QUAZEPAM

Absorption

The half-life of absorption following oral administration is approximately 30 minutes. Peak plasma concentration (Cmax) is approximately 20 ng/mL and occurs around 2 hours following administration.

Toxicity

Benzodiazepine overdose is typically characterized by central nervous system depression ranging from mild drowsiness to coma. Mild-to-moderate cases may involve relatively minor symptoms like drowsiness, dysarthria, confusion, and ataxia, while severe cases may lead to respiratory depression and coma. In rare cases, paradoxical disinhibitory reactions (e.g. agitation, violent behaviour, impulsivity) may occur.
The management of benzodiazepine overdose should involve general supportive measures as clinically indicated. Flumazenil is a benzodiazepine receptor antagonist which is indicated for the complete or partial reversal of benzodiazepine-induced sedation, although its appropriateness is highly dependent on the clinical status and history of the patient. The use of flumazenil can lead to withdrawal and significant adverse reactions (e.g. seizures), especially in the context of mixed overdoses and in long-term benzodiazepine users with an established physical dependency, and its use is contraindicated in patients using benzodiazepines for potentially life-threatening conditions (e.g. status epilepticus). If the decision is made to use flumazenil, it should be used as specified in its prescribing information and as an adjunct alongside general supportive management.

Description

Quazepam is a rapidly acting, short term hypnotic reported to exhibit a low incidence of side effects.

Originator

Schering (USA)

The Uses of QUAZEPAM

Quazepam is a benzodiazepine derivative drug and is known to bind nonspecifically to benzodiazepine receptors, which affects muscle relaxation, anticonvulsant activty, motor coordination and memory. Quazepam is known to induce motor impairment and exerts hypnotic properties. Quazepam is often used for the treatment of insomina.

Background

Quazepam is a trifluoroethyl benzodiazepine derivative. It was first approved in the US in 1985 and is used as a hypnotic for the treatment of insomnia.
It appears to be unique amongst other benzodiazepine derivatives in its relatively high affinity for sleep-promoting α1 subunit-containing GABAA receptors and low affinity for other receptors.

Indications

Quazepam is indicated for the treatment of insomnia characterized by difficulty falling asleep, frequent nocturnal awakenings, and/or early morning awakenings.

Definition

ChEBI: Quazepam is a benzodiazepine.

brand name

Doral (Questcor).

General Description

Quazepam (Doral) and its active metabolitesreportedly are relatively selective for the benzodiazepinemodulatory site on GABA_A receptors with α1 subunitand are hypnotic agents. Quazepam is metabolized by oxidation to the 2-oxo compound and then N-dealkylation.Both metabolites are active; the first reportedly is the morepotent and selective. Thereafter, 3-hydroxylation and glucuronidationoccur.

Pharmacokinetics

Benzodiazepines, including quazepam, exert their sedative and anxiolytic effects by potentiating the effects of endogenous GABA, the primary inhibitory neurotransmitter in the central nervous system.

Metabolism

Quazepam undergoes extensive hepatic metabolism, primarily via CYP3A4 and to a lesser extent via CYP2C9, CYP2C19, and FMO1. Quazepam is first metabolized to 2-oxoquazepam, which is then further metabolized to both N-desalkyl-2-oxoquazepam (norflurazepam) and 3-hydroxy-2-oxoquazepam. Both 2-oxoquazepam and N-desalkyl-2-oxoquazepam exert CNS depressant activity.