I Although diazepam has been the benzodiazepine of choice for status epilepticus, recent evidence indicates that lorazepam may be more beneficial because it provides longer control of seizures and produces less cardiorespiratory depression. Diazepam was approved by the FDA in November Phase III data for a rectal formulation of diazepam in the treatment of acute repetitive seizures was completed April The NDA for the rectal formulation Diastat is expected to be filed in Diazepam is a schedule IV controlled substance.
Benzodiazepines act at the level of the limbic, thalamic, and hypothalamic regions of the CNS, and can produce any level of CNS depression required including sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and coma. The action of these drugs is mediated through the inhibitory neurotransmitter gamma-aminobutyric acid GABA.
Central benzodiazepine receptors interact allosterically with GABA receptors, potentiating the effects of GABA and increasing the inhibition of the ascending reticular activating system.
Evidence suggests that GABA receptors are heterogeneous with many different subtypes, which may account for the various effects of GABA receptor agonists and benzodiazepines. Midazolam, for example, has twice the affinity for benzodiazepine receptors than diazepam. The antianxiety action of benzodiazepines may be a result of their ability to block cortical and limbic arousal following stimulation of the reticular pathways while muscle relaxation properties are mediated by inhibiting both mono-and polysynaptic pathways.
Benzodiazepine can also depress muscle and motor nerve function directly. Animal studies of the anticonvulsant actions suggest that benzodiazepines augment presynaptic inhibition of neurons, thereby limiting the spread of electrical activity, although they do not actually inhibit the abnormally discharging focus. Benzodiazepines may also have other actions.
For example, diazepam has been shown to counteract the cardiovascular toxicity of chloroquine. It is thought that diazepam increases the urinary clearance of chloroquine by improving electrocardiographic and hemodynamic function. Diazepam is administered orally and parenterally. A viscous solution intended for rectal administration in undergoing investigation. Diazepam is the most rapidly absorbed benzodiazepine following an oral dose; however, absorption following an IM injection is slow and erratic.
Anticonvulsant, skeletal muscle relaxant, and anxiolytic effects are usually evident after the first dose. The onset of action after an IV dose is minutes. The duration for some clinical effects e. Diazepam is widely distributed, with CSF levels similar to plasma levels. This benzodiazepine crosses the placenta and distributes into breast milk see Contraindications.
The disparity between elimination half-life and duration of action for some conditiona may be partially explained by rapid shifts in distribution of diazepam out of the CNS. The half-life of diazepam is hours. Not all this advertising is credible. No matter how highly regarded a website is, it often can't control the ads found on its site because those ads may be managed by a third party. So, be aware that you will have to determine the safety and legality of ordering from any of those companies that advertise, even on highly respected sites.
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