WBR1004

Author	[[PageAuthor::Vidit Bhargava, M.B.B.S [1] (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 5-year-old child is brought to the pediatrics clinic by concerned parents. He is reported to have occasional episodes of “staring into space” which last about 1-2 mins during which the child is unarousable even with painful stimuli but does not seem disoriented after he regains consciousness. The parents deny any jerky movements or tonic muscle spasms. Overnight monitoring with electroencephalogram demonstrates 3 Hz spike-and-slow wave complexes during one of the episodes. What is the mechanism of action of drug most commonly used to treat this condition?]]
Answer A	[[AnswerA::Blocking T-type Ca2+ channels]]
Answer A Explanation	[[AnswerAExp::Ethosuximide, the first line therapy for absence seizures, blocks T-type Ca2+ channels, decreasing membrane excitability of neurons.]]
Answer B	[[AnswerB::Decreasing influx of Na+ across cell membrane channels]]
Answer B Explanation	AnswerBExp::This is the most common mechanism of action by which a number of anti epileptic drugs act such as carbamazepine, phenytoin, fosphenytoin.
Answer C	AnswerC::Inhibiting GABA transaminase
Answer C Explanation	AnswerCExp::This is the main mechanism of action of vigabatrin.
Answer D	[[AnswerD::Decreasing influx of Na+ across cell membrane channels, and increasing the inhibitory activity of GABA]]
Answer D Explanation	AnswerDExp::This is the main mechanism of action of valproic acid. Although it is indicated for absence seizures, ethosuxamide is preferred.
Answer E	AnswerE::Antagonizing AMPA/kainate glutamate receptors
Answer E Explanation	AnswerEExp::Antagonism of AMPA/kainite receptors is one of the several mechanisms by which topiramate acts.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Absence seizures, also known as a staring spells or petit-mal seizures, are a form of epilepsy most commonly observed among children between the ages of 6 and 12. Absence seizures are characterized by brief episodes (classically a few seconds, may last up to 30 seconds) of impairment of consciousness associated with and interruption of activity and a blank stare that usually start and end very abruptly without a post-ictal phase of confusion. These episodes may go unnoticed and mistaken for attention deficit. Absence seizures may be diagnosed when working up a young child with learning disabilities. Definite diagnosis is by electroencephalogram (EEG) demonstrating typical 3 Hz spike-and-slow wave complexes during an absence episode. These seizures may be triggered by hyperventilation, which may be used in the clinic to aid the diagnosis. The first line therapy for absence seizures is ethosuximide. Ethosuxamide blocks T-type Ca2+ channel thus decreasing membrane excitability. Valproic acid is a second line option for patients who cannot tolerate ethosuxamide, or are not well controlled. Educational Objective: Ethosuximide, the first line therapy for absence seizures, blocks T-type Ca2+ channels, decreasing membrane excitability of neurons. References: First Aid Step 1 2013 p. 451]]
Approved	Approved::Yes
Keyword	WBRKeyword::Ethosuximide, WBRKeyword::Absence seizure, WBRKeyword::Petit mal, WBRKeyword::Valproic acid, WBRKeyword::Epilepsy, WBRKeyword::Anti-epileptics, WBRKeyword::Antiepileptics, WBRKeyword::Mechanism of action
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