An 8-year-old boy is brought to the office by his mother for a routine checkup. He was diagnosed with absence seizures a year ago and has been undergoing treatment with an appropriate antiepileptic agent. The mother says that the patient is doing well and has not had any seizures since starting the medication. His school performance has improved significantly, and he no longer gets in trouble for "staring off" in class. He eats a well-balanced diet and is at the 50th percentile for height and weight. Which of the following is the most likely mechanism of action of the medication used in this patient?

Question

An 8-year-old boy is brought to the office by his mother for a routine checkup.  He was diagnosed with absence seizures a year ago and has been undergoing treatment with an appropriate antiepileptic agent.  The mother says that the patient is doing well and has not had any seizures since starting the medication.  His school performance has improved significantly, and he no longer gets in trouble for "staring off" in class.  He eats a well-balanced diet and is at the 50th percentile for height and weight.  Which of the following is the most likely mechanism of action of the medication used in this patient?

Quizplus · Accepted Answer

11ec160b_3c1b_d170_9249_edcb0d242da0_MD0001_00 Ethosuximide is the first-line treatment for absence seizures. This drug blocks T-type Ca²⁺ channels that trigger and sustain rhythmical burst discharges in thalamic neurons. Side effects of this drug are minimal and include nausea, vomiting, fatigue, and hyperactivity. If ethosuximide is not tolerated due to these side effects, or if the drug is ineffective in suppressing seizure activity, valproic acid is used as a second-line treatment for absence epilepsy. Valproic acid is a broad-spectrum antiseizure drug that inhibits voltage-dependent Na⁺ channels and also causes a rise in GABA concentration. (Choice A) Benzodiazepines and barbiturates (eg, phenobarbital) bind to GABA receptors and allow an increased chloride current through the ion channel. This hyperpolarizes the cell membrane, which increases the threshold of excitability of the postsynaptic neuron. (Choice B) Levetiracetam binds to a synaptic vesicle protein (SV2A) to modulate the release of GABA and glutamate neurotransmitters. (Choice D) Phenytoin decreases the sodium current in cortical neurons by reducing the ability of sodium channels to recover from inactivation. This increases the refractory period of the neuron, inhibiting neuronal high-frequency firing. Carbamazepine and valproic acid have similar mechanisms of action. (Choice E) Increasing the levels of brain beta-hydroxybutyrate acid (ketone bodies) is the goal of the ketogenic diet. This high-fat, low-carbohydrate diet may benefit some patients with refractory epilepsy. Educational objective: Ethosuximide, the first-line treatment for absence seizures, prevents neuronal burst firing by blocking thalamic T-type Ca²⁺ channels. Phenytoin, carbamazepine, and valproic acid inhibit neuronal high-frequency firing by reducing the ability of Na⁺ channels to recover from inactivation. __________ References: T-type Ca2+ channels in absence epilepsy. (http://www.ncbi.nlm.nih.gov/pubmed/24519464)

An 8-Year-Old Boy Is Brought to the Office by His