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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Rim}}
|QuestionAuthor= {{SSK}} {{Alison}} (Reviewed by Serge Korjian)
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Pharmacology
|MainCategory=Pharmacology
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|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=Neurology
|SubCategory=Neurology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
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|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=Neurology
|SubCategory=Neurology
|Prompt=A 28 year old male patient who is previously healthy is brought to the emergency department for excessive somnolence, impaired balance, and impaired motor function.  The physician suspects a benzodiazepine overdose.  Flumazenil is quickly administered at the appropriate dose and infusion rate.  A few seconds after administration of flumazenil, the patient’s wife arrives to the emergency department and tells the physician that her husband attempted suicide and in fact ingested excessively two drugs: A benzodiazepine and a tricyclic antidepressant.  Which of the following symptoms will the patient most likely experience following administration of flumazenil in this case of co-ingestion of benzodiazepine and tricyclic antidepressant?
|Prompt=A 28-year-old man is brought to the emergency department for excessive somnolence and impaired motor function.  Suspecting a benzodiazepine overdose, flumazenil is immediately administered.  A few seconds following the administration of flumazenil, the patient’s wife arrives to the emergency department and confirms that her husband likely attempted suicide by ingesting a handful of her anxiety pills which include lorazepam and fluoxetine.  Which of the following symptoms will the patient most likely experience following the administration of flumazenil?
|Explanation=[[Flumazenil]] should be used carefully in patients who have a previous history of [[seizures]], such as a past medical history of [[epilepsy]], or when there is suspicion of mixed [[overdose]]. In the case when [[benzodiazepine]] ([[BZD]]) is co-ingested with [[tricyclic antidepressants]] ([[TCA]]), the use of flumazenil as an antidote to benzodiazepine to reverse the sedative effects of benzodiazepines can actually expose or unmask the side effect of tricyclic antidepressants, such as seizures, that can occur within only a few minutes of administration of flumazenil.  The seizure is not believed to be a side effect of flumazenil itself, but rather an unmasking of the side effect of the tricyclic antidepressant that is apparent only when the effect of benzodiazepine is reversed by flumazenil.
|Explanation=[[Flumazenil]] is a  GABA<sub>A</sub> receptor antagonist used primarily for the treatment of benzodiazepine overdoses. Flumazenil should be used carefully in patients who have a history of seizures, such as epilepsy, or when there is suspicion of a mixed overdose. The use of flumazenil, when a benzodiazepine is co-ingested with tricyclic antidepressants (TCA), often manifests with seizures, a side effect of TCAs.  The seizure is not believed to be a side effect of flumazenil itself, rather one of TCAs that occurs when the effect of the benzodiazepine is reversed but that of the TCA is not.
 
As a result, seizure risk must always be assessed in patients who require flumazenil use and a risk-to-benefit ratio in those patients must always be considered as to whether flumazenil is to be administered or not.  
 
Educational Objective:
In the case when benzodiazepine (BZD) is co-ingested with tricyclic antidepressants (TCA), the use of flumazenil as an antidote to benzodiazepine to reverse the sedative effects of benzodiazepines can actually unmask the side effect of tricyclic antidepressants, such as seizures, that can occur within a few minutes of administration of flumazenil. 
 
References:
Spivey WH. Flumazenil and seizures: analysis of 43 cases. Clin Ther. 1992; 14(2):292-305.
 
Haverkos GP, DiSalvo RP, Imhoff TE. Fatal seizures after flumazenil administration in a patient with mixed overdose. Ann Pharmacother. 1994;28(12):1347-9.
 
|AnswerA=Seizure
|AnswerA=Seizure
|AnswerAExp=Seizure is a potential adverse event in the case of flumazenil antidote of when co-ingestion of BZD and TCA.
|AnswerAExp=The use of flumazenil, when a benzodiazepine (BZD) is co-ingested with TCA, often manifests with seizures.
|AnswerB=Chest pain
|AnswerB=Chest pain
|AnswerBExp=Chest pain is not an adverse effect of flumazenil use in this case.
|AnswerBExp=Chest pain is not an adverse effect of flumazenil use in this scenario.
|AnswerC=Excessive sedation
|AnswerC=Excessive sedation
|AnswerCExp=Flumazenil is expected to reverse the excessive sedation that is caused by BZD.
|AnswerCExp=Flumazenil is expected to reverse the excessive sedation that is caused by benzodiazepines.
|AnswerD=Renal failure
|AnswerD=Renal failure
|AnswerDExp=Renal failure is not an adverse effect of flumazenil use in this case.
|AnswerDExp=Renal failure is not an adverse effect of flumazenil use in this scenario.
|AnswerE=Acalculous cholecystitis
|AnswerE=Acalculous cholecystitis
|AnswerEExp=Acalculous cholecystitis is not an adverse effect of flumazenil use in this case.
|AnswerEExp=Acalculous cholecystitis is not an adverse effect of flumazenil use in this scenario.
|EducationalObjectives=The use of flumazenil, when a benzodiazepine is co-ingested with tricyclic antidepressants (TCA), often manifests with seizures.  The seizure is not believed to be a side effect of flumazenil itself, rather one of tricyclic antidepressants that occurs when the effect of a benzodiazepine is reversed.
|References=Spivey WH. Flumazenil and seizures: analysis of 43 cases. Clin Ther. 1992; 14(2):292-305.<br>
Haverkos GP, DiSalvo RP, Imhoff TE. Fatal seizures after flumazenil administration in a patient with mixed overdose. Ann Pharmacother. 1994;28(12):1347-9.
|RightAnswer=A
|RightAnswer=A
|WBRKeyword=benzodiazepine, tricyclic, antidepressant, flumazenil, seizure, adverse, drug, reaction, side, effect, coingestion, mixed, overdose
|WBRKeyword=Benzodiazepine, Tricyclic antidepressant, Flumazenil, Seizure, Mixed overdose, Suicide
|Approved=No
|Approved=Yes
}}
}}

Latest revision as of 00:35, 28 October 2020
Author [[PageAuthor::Serge Korjian 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 28-year-old man is brought to the emergency department for excessive somnolence and impaired motor function. Suspecting a benzodiazepine overdose, flumazenil is immediately administered. A few seconds following the administration of flumazenil, the patient’s wife arrives to the emergency department and confirms that her husband likely attempted suicide by ingesting a handful of her anxiety pills which include lorazepam and fluoxetine. Which of the following symptoms will the patient most likely experience following the administration of flumazenil?]]
Answer A AnswerA::Seizure
Answer A Explanation AnswerAExp::The use of flumazenil, when a benzodiazepine (BZD) is co-ingested with TCA, often manifests with seizures.
Answer B AnswerB::Chest pain
Answer B Explanation AnswerBExp::Chest pain is not an adverse effect of flumazenil use in this scenario.
Answer C AnswerC::Excessive sedation
Answer C Explanation AnswerCExp::Flumazenil is expected to reverse the excessive sedation that is caused by benzodiazepines.
Answer D AnswerD::Renal failure
Answer D Explanation AnswerDExp::Renal failure is not an adverse effect of flumazenil use in this scenario.
Answer E AnswerE::Acalculous cholecystitis
Answer E Explanation AnswerEExp::Acalculous cholecystitis is not an adverse effect of flumazenil use in this scenario.
Right Answer RightAnswer::A
Explanation [[Explanation::Flumazenil is a GABAA receptor antagonist used primarily for the treatment of benzodiazepine overdoses. Flumazenil should be used carefully in patients who have a history of seizures, such as epilepsy, or when there is suspicion of a mixed overdose. The use of flumazenil, when a benzodiazepine is co-ingested with tricyclic antidepressants (TCA), often manifests with seizures, a side effect of TCAs. The seizure is not believed to be a side effect of flumazenil itself, rather one of TCAs that occurs when the effect of the benzodiazepine is reversed but that of the TCA is not.

Educational Objective: The use of flumazenil, when a benzodiazepine is co-ingested with tricyclic antidepressants (TCA), often manifests with seizures. The seizure is not believed to be a side effect of flumazenil itself, rather one of tricyclic antidepressants that occurs when the effect of a benzodiazepine is reversed.
References: Spivey WH. Flumazenil and seizures: analysis of 43 cases. Clin Ther. 1992; 14(2):292-305.
Haverkos GP, DiSalvo RP, Imhoff TE. Fatal seizures after flumazenil administration in a patient with mixed overdose. Ann Pharmacother. 1994;28(12):1347-9.]]

Approved Approved::Yes
Keyword WBRKeyword::Benzodiazepine, WBRKeyword::Tricyclic antidepressant, WBRKeyword::Flumazenil, WBRKeyword::Seizure, WBRKeyword::Mixed overdose, WBRKeyword::Suicide
Linked Question Linked::
Order in Linked Questions LinkedOrder::
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