A 5-year-old boy is brought to the emergency department due to recurrent, generalized tonic-clonic seizures over the past 24 hours. The patient has been having high fever and flulike symptoms for the past 3 days. He has a past medical history of febrile seizures at age 6 months. He takes no medications and has no family history of epilepsy. The patient's temperature is 39.4 C (103 F), blood pressure is 110/70 mm Hg, pulse is 112/min, and respirations are 10/min. He appears lethargic and does not follow simple commands consistently. His neck is supple. During the examination, the patient suddenly develops sustained, generalized tonic-clonic convulsions without fully regaining consciousness between episodes. Which of the following describes the mechanism of action of the most appropriate initial therapy for his seizures?

Question

A 5-year-old boy is brought to the emergency department due to recurrent, generalized tonic-clonic seizures over the past 24 hours.  The patient has been having high fever and flulike symptoms for the past 3 days.  He has a past medical history of febrile seizures at age 6 months.  He takes no medications and has no family history of epilepsy.  The patient's temperature is 39.4 C (103 F), blood pressure is 110/70 mm Hg, pulse is 112/min, and respirations are 10/min.  He appears lethargic and does not follow simple commands consistently.  His neck is supple.  During the examination, the patient suddenly develops sustained, generalized tonic-clonic convulsions without fully regaining consciousness between episodes.  Which of the following describes the mechanism of action of the most appropriate initial therapy for his seizures?

Quizplus · Accepted Answer

This patient has status epilepticus, possibly due to complex febrile seizures or infectious meningitis/encephalitis. Regardless of etiology, the initial drug of choice for treating status epilepticus is an intravenous benzodiazepine (eg, lorazepam), due to its efficacy and rapid onset of action. Benzodiazepines enhance the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) at the GABA-A receptor, a ligand-gated ion channel. Allosteric attachment of benzodiazepines to the GABA-A receptor causes increased influx of negatively charged chloride ions in response to GABA binding. This leads to hyperpolarization of the postsynaptic neuron and suppression of action potential firing (anticonvulsant effect). (Choices A and E) Presynaptic voltage-gated calcium channels mediate the influx of calcium into the axon terminal, promoting vesicle fusion and neurotransmitter release into the synaptic cleft. Gabapentin is an anticonvulsant that works by blocking voltage-gated calcium channels, thereby attenuating excitatory neurotransmitter release. (Choice B) Presynaptic voltage-gated sodium channels open when the cell becomes sufficiently depolarized, triggering an action potential that propagates down the axon. Phenytoin blocks presynaptic voltage-gated sodium channels and can be used to prevent recurrence of status epilepticus due to its long duration of action. However, it has a slow onset of action, and patients in status epilepticus should be given a rapid-acting benzodiazepine first. (Choice D) Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are examples of medications that prevent presynaptic neurotransmitter reuptake. They are typically used to treat depression and anxiety disorders. Educational objective: Intravenous benzodiazepines (eg, lorazepam) are the initial drug of choice for status epilepticus. They work by enhancing the effect of gamma-aminobutyric acid (GABA) at the GABA-A receptor, leading to increased chloride influx and suppression of action potential firing. __________ References: Benzodiazepine pharmacology and central nervous system-mediated effects. (http://www.ncbi.nlm.nih.gov/pubmed/23789008) Pharmacotherapy for Status Epilepticus. (http://www.ncbi.nlm.nih.gov/pubmed/26310189)

A 5-Year-Old Boy Is Brought to the Emergency Department Due