indication

For the treatment of anxiety disorders and alcohol withdrawal.

pharmacology

Oxazepam is believed to stimulate GABA receptors in the ascending reticular activating system. Since GABA is inhibitory, receptor stimulation increases inhibition and blocks both cortical and limbic arousal following stimulation of the brain stem reticular formation.

mechanism of action

Similar to other benzodiazepines, oxazepam exerts its anxiolytic effects by potentiating the effect of gamma-aminobutyric acid (GABA) on GABA-A receptors through a cooperative mechanism of action. GABA receptors are ionotropic chloride-linked channel receptors that produce inhibitory postsynaptic potentials. When activated by GABA, the GABA receptor/chloride ionophore complex undergoes a conformational change that allows the passage of chloride ions through the channel. Benzodiazepines are believed to exert their effect by increasing the effect of GABA at its receptor. Benzodiazepine binding increases chloride conductance in the presence of GABA by increasing the frequency at which the channel opens. In contrast, barbiturates increase chloride conductance in the presence of GABA by prolonging the time in which the channel remains open. There are 18 subtypes of the GABA receptor subunits. The α₂ subunit of the α₂β₃γ₂ receptor complex is thought to mediate anxiolytic effects while the α₁ subunit of the α₁β₂γ₂ receptor complex is thought to mediate sedative, anticonvulsant and anterograde amnesia effects.

toxicity

Symptoms of overdose include confusion, drowsiness, and lethargy.

biotransformation

No active metabolites. Metabolized via conjugation prior to elimination.

absorption

Well absorbed from the gastrointestinal tract following oral administration. Time to peak concentration = 2-4 hours. Onset of action is slow, > 3 hours, following oral administration.

half life

5-15 hours

route of elimination

This product has a single, major inactive metabolite in man, a glucuronide excreted in the urine.

drug interactions

Clozapine: Increased risk of toxicity

Kava: Kava may increase the effect of the benzodiazepine, oxazepam.

Triprolidine: The CNS depressants, Triprolidine and Oxazepam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.