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A patient arrives in the ED via EMS having a grand mal seizure. The ED physician...

A patient arrives in the ED via EMS having a grand mal seizure. The ED physician instructs the RN to give 10 milligrams of Diazepam IV X1 dose STAT. The patient’s seizure breaks within 2 minutes of the Diazepam being administered. The mechanism by which this medication causes rapid resolution of seizure activity is via which receptor type (effector pathway/receptor subtype)

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Answer #1

Benzodiazepines exert their effects by facilitating the activity of GABA at various sites. Specifically, benzodiazepines bind at an allosteric site at the interface between the alpha and gamma subunits on GABA-A receptor chloride ion channels. The allosteric binding of diazepam at the GABA-A receptor leads to an increase in the frequency at which the chloride channel opens, leading to an increased conductance of chloride ions. This shift in charge leads to a hyperpolarization of the neuronal membrane and reduced excitability of the neuron.[3]

Specifically, the allosteric binding within the limbic system leads to the anxiolytic effects seen with diazepam. Allosteric binding within the spinal cord and motor neurons is the primary mediator of the myorelaxant effects seen with diazepam. Mediation of the sedative, amnestic, and anticonvulsant effects of diazepam is through receptor binding within the cortex, thalamus, and cerebellum.[4]

Once in the body, diazepam is mostly broken down by the CYP2C19 and CYP3A4 enzymes to several active metabolites, mainly desmethyldiazepam. Other minor active metabolites include oxazepam and temazepam. The average half-life of oral diazepam and desmethyldiazepam are about 46 hours and 100 hours, respectively. Potent inhibition of the 2C19 enzyme by certain drugs (fluoxetine and chloramphenicol) and 3A4 enzymes by certain medications (ketoconazole, protease inhibitors, erythromycin) may cause increased levels of diazepam, while inducers of 2C19 (rifampicin and prednisone) and 3A4 (carbamazepine, topiramate, phenytoin, St. John's wort, rifampin, or barbiturates) may cause lower levels. Metabolites of diazepam are conjugated with glucuronide and excreted almost entirely in the urine.
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