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|QuestionAuthor={{Rim}}
|QuestionAuthor= {{YD}} {{Alison}} (Reviewed by Serge Korjian)
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Pharmacology
|MainCategory=Pharmacology
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|Prompt=A 10 year old boy is brought by his mother to the physician's office for recurrent abrupt transient loss of consciousness and a blank stare. Following appropriate work-up, the patient is diagnosed with absence seizure.  The patient is started on a new medication to treat his condition.  Which of the following best describes the mechanism of action of the prescribed medication?
|Prompt=A 10-year-old boy is brought to the pediatrician's office for declining school performance and poor concentration. The mother explains that her child is a day dreamer and is concerned about his recurrent blank stares. She is fearful that her son has attention deficit disorder (ADD). Following an extensive work-up, the patient is diagnosed with seizure disorder and treatment is initiated.  Which of the following mechanisms of action corresponds to the medication prescribed to this patient?
|Explanation=Ethosuximide is a succinimide antiepileptic drug that is considered the first line treatment for absence seizure (petit mal). It is a low voltage-activated thalamic T-type calcium channel blocker.   
|Explanation=[[Absence seizures]] are described as episodes of succint lapse of consciousness or “blanking out”. Simple absence seizures are often very short in duration that they may be undetectable without electroencephalography (EEG) and may be easily confused with daydreaming or lack attention and concentration. Absence seizures do not have a post-ictal phase; patients usually continue the same activities they were performing prior to the seizure onset. Absence epilepsy (recurrent absence seizures) occurs most commonly among children aged 4-15 years. The EEG classically shows 3-Hz spike-and-slow-wave complexes after a seizure is triggered by hyperventilation. [[Ethosuximide]], a succinimide antiepileptic drug, is the first line treatment for absence seizure (petit mal). It is a low voltage-activated thalamic T-type calcium channel blocker.  Ethosuximide has a rare frequency of adverse drug reactions. The most common side effects include GI distress, fatigue, and headache. Valproic acid may also be used to treat absence seizures as second line therapy.
 
Ethosuximide has a relatively safe side effect profile with a rare frequency of adverse drug reactions. Most common side effects include GI distress, fatigue and headache. A less common, but more severe side effect is Stevens-Johnson syndrome, a dermatologic disorder characterized by fever, bullous formation, and necrosis with skin sloughing.
 
In addition to ethosuximide, valproic acid can often be used to treat absence seizures as well.
 
Educational Objective: Ethosuxamide is the first line treatment for absence seizures.  It is a thalamic T-type calcium channel blocker.
|AnswerA=Inactivation of dopamine receptors
|AnswerA=Inactivation of dopamine receptors
|AnswerAExp=Antipsychotics are used to treat psychiatric diseases, such as schizophrenia, act by inactivation of dopamine receptors.
|AnswerAExp=Antipsychotics used to treat psychiatric diseases such as schizophrenia act by inactivation of dopamine receptors.
|AnswerB=Inactivation of sodium channels but not effect on GABA
|AnswerB=Inactivation of sodium channels
|AnswerBExp=Phenytoin is not commonly used for absence seizures.  It is used, however, in tonic-clonic generalized seizure and partial seizures. Its mechanism of action is inactivation of sodium channels.  
|AnswerBExp=Phenytoin's mechanism of action is the inactivation of sodium channels. Although phenytoin is not commonly administered to treat absence seizures, it is used in tonic-clonic generalized seizures and partial seizures.
 
|AnswerC=Activation of GABA receptors
Also, carbamazepine is not first line treatment for absence seizures.  It is a first line treatment for partial seizures and tonic-clonic generalized seizures.  Similar to phenytoin, carbamazepine acts by inactivation of sodium channels.
|AnswerCExp=Topiramate activates GABA receptors. It is not commonly administered to treat absence seizures, but is effective in treating partial and tonic-clonic generalized seizures.
|AnswerC=Concomitant inactivation of sodium channels and activation of GABA
|AnswerCExp=Topiramate blocks sodium channels and increases the action of GABA. It is not commonly used in absence seizures.  It is effective in partial and tonic-clonic generalized seizures.
 
|AnswerD=Inactivation of thalamic T-type calcium channels
|AnswerD=Inactivation of thalamic T-type calcium channels
|AnswerDExp=Ethosuximide is considered first line treatment for absence seizures.  It blocks thalamic T-type calcium channels.
|AnswerDExp=Ethosuxamide, the first line treatment for absence seizures, is a thalamic T-type calcium channel blocker.
|AnswerE=Inhibition of GABA reuptake
|AnswerE=Inhibition of GABA reuptake
|AnswerEExp=Tiagabine is effective in partial seizures.  It acts by inhibition of GABA reuptake.  It is not usually used to treat absence seizures.
|AnswerEExp=Tiagabine, which acts by inhibition of GABA reuptake, is effective in partial seizures, but is not usually used to treat absence seizures.
|EducationalObjectives=[[Ethosuxamide]], the first line treatment for absence seizures, is a thalamic T-type calcium channel blocker.
|References=Glauser TA, Cnaan A, Shinnar S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med. 2010;362(9):790-9.
|RightAnswer=D
|RightAnswer=D
|WBRKeyword=absence, seizure, seizures, petit, mal, petit mal, ethosuximide, calcium, channel, blocker, t-type, t type, thalamic, mechanism, action
|WBRKeyword=Absence seizure, Seizure, Petit mal, Ethosuximide, Calcium channel blocker, T-type, Mechanism of action, Neurological,
|Approved=No
|Approved=Yes
}}
}}

Latest revision as of 00:53, 28 October 2020

 
Author [[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Alison Leibowitz) (Reviewed by Serge Korjian)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Pharmacology
Sub Category SubCategory::Neurology
Prompt [[Prompt::A 10-year-old boy is brought to the pediatrician's office for declining school performance and poor concentration. The mother explains that her child is a day dreamer and is concerned about his recurrent blank stares. She is fearful that her son has attention deficit disorder (ADD). Following an extensive work-up, the patient is diagnosed with seizure disorder and treatment is initiated. Which of the following mechanisms of action corresponds to the medication prescribed to this patient?]]
Answer A AnswerA::Inactivation of dopamine receptors
Answer A Explanation AnswerAExp::Antipsychotics used to treat psychiatric diseases such as schizophrenia act by inactivation of dopamine receptors.
Answer B AnswerB::Inactivation of sodium channels
Answer B Explanation AnswerBExp::Phenytoin's mechanism of action is the inactivation of sodium channels. Although phenytoin is not commonly administered to treat absence seizures, it is used in tonic-clonic generalized seizures and partial seizures.
Answer C AnswerC::Activation of GABA receptors
Answer C Explanation AnswerCExp::Topiramate activates GABA receptors. It is not commonly administered to treat absence seizures, but is effective in treating partial and tonic-clonic generalized seizures.
Answer D AnswerD::Inactivation of thalamic T-type calcium channels
Answer D Explanation AnswerDExp::Ethosuxamide, the first line treatment for absence seizures, is a thalamic T-type calcium channel blocker.
Answer E AnswerE::Inhibition of GABA reuptake
Answer E Explanation AnswerEExp::Tiagabine, which acts by inhibition of GABA reuptake, is effective in partial seizures, but is not usually used to treat absence seizures.
Right Answer RightAnswer::D
Explanation [[Explanation::Absence seizures are described as episodes of succint lapse of consciousness or “blanking out”. Simple absence seizures are often very short in duration that they may be undetectable without electroencephalography (EEG) and may be easily confused with daydreaming or lack attention and concentration. Absence seizures do not have a post-ictal phase; patients usually continue the same activities they were performing prior to the seizure onset. Absence epilepsy (recurrent absence seizures) occurs most commonly among children aged 4-15 years. The EEG classically shows 3-Hz spike-and-slow-wave complexes after a seizure is triggered by hyperventilation. Ethosuximide, a succinimide antiepileptic drug, is the first line treatment for absence seizure (petit mal). It is a low voltage-activated thalamic T-type calcium channel blocker. Ethosuximide has a rare frequency of adverse drug reactions. The most common side effects include GI distress, fatigue, and headache. Valproic acid may also be used to treat absence seizures as second line therapy.

Educational Objective: Ethosuxamide, the first line treatment for absence seizures, is a thalamic T-type calcium channel blocker.
References: Glauser TA, Cnaan A, Shinnar S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med. 2010;362(9):790-9.]]

Approved Approved::Yes
Keyword WBRKeyword::Absence seizure, WBRKeyword::Seizure, WBRKeyword::Petit mal, WBRKeyword::Ethosuximide, WBRKeyword::Calcium channel blocker, WBRKeyword::T-type, WBRKeyword::Mechanism of action, WBRKeyword::Neurological
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