A 17-year-old girl is brought to the emergency department after an episode of syncope. The patient was sitting on the couch watching television when she suddenly passed out. She had no symptoms prior to the event and regained consciousness spontaneously after approximately 2 minutes. Her family noticed a brief twitching while the patient was unconscious, but she had no tongue biting or bowel or bladder incontinence. The patient is taking an antimicrobial agent for a recent infection but has no other chronic medical conditions. Her uncle died suddenly 2 years ago. A detailed evaluation reveals a decrease-in-function mutation in the KCNH2 gene, which codes for a voltage-gated potassium channel that is active during the repolarization phase of cardiomyocyte action potential. The patient's medication was causing further impairment of the ion channel function, leading to the incident of syncope. This patient was most likely taking which of the following medications?

Question

A 17-year-old girl is brought to the emergency department after an episode of syncope.  The patient was sitting on the couch watching television when she suddenly passed out.  She had no symptoms prior to the event and regained consciousness spontaneously after approximately 2 minutes.  Her family noticed a brief twitching while the patient was unconscious, but she had no tongue biting or bowel or bladder incontinence.  The patient is taking an antimicrobial agent for a recent infection but has no other chronic medical conditions.  Her uncle died suddenly 2 years ago.  A detailed evaluation reveals a decrease-in-function mutation in the KCNH2 gene, which codes for a voltage-gated potassium channel that is active during the repolarization phase of cardiomyocyte action potential.  The patient's medication was causing further impairment of the ion channel function, leading to the incident of syncope.  This patient was most likely taking which of the following medications?

Quizplus · Accepted Answer

11ec160b_3b90_0c43_9249_4ba56f3103da_MD0001_00 A decrease-in-function mutation affecting the KCNH2 gene is one of the most common causes of congenital long QT syndrome (LQTS); it can be inherited in autosomal dominant (Romano-Ward syndrome) or autosomal recessive (Jervell and Lange-Nielsen syndrome) fashion. The mutation impairs the function of the voltage-gated potassium channels controlling the delayed rectifier potassium current that allows repolarization of the cardiomyocyte action potential. Delayed repolarization manifests as a prolonged QT interval on ECG and predisposes to the development of torsades de pointes (TdP) (a form of polymorphic ventricular tachycardia), which can cause syncope or sudden cardiac death. Most patients with underlying congenital LQTS do not develop TdP unless exposed to an external influence. Medications are the most common cause of acquired LQTS and the most important exacerbating factor in patients with congenital LQTS. Most medications that prolong the QT interval do so by delaying the repolarizing potassium current via blockade of the same voltage-gated potassium channels affected by the KCNH2 gene mutation. Macrolide antibiotics (eg, erythromycin, azithromycin) prolong the QT interval and increase the risk of TdP, especially in patients with underlying congenital LQTS. Other medications that prolong the QT interval include fluoroquinolone antibiotics (eg, ciprofloxacin, moxifloxacin) and many antipsychotics (eg, haloperidol, risperidone) and antiemetics (eg, ondansetron, metoclopramide). The coadministration of multiple QT-prolonging medications may precipitate TdP in patients without congenital LQTS. (Choice A) Some antiviral medications may prolong the QT interval-including protease inhibitors used in the treatment of HIV (eg, saquinavir, atazanavir)-however, acyclovir does not. (Choices B, C, and D) Penicillins (eg, amoxicillin), cephalosporins (eg, cephalexin), and tetracyclines (eg, doxycycline) have not been shown to prolong the QT interval. (Choice F) Azoles (eg, fluconazole, voriconazole) prolong the QT interval; however, most other antifungal medications, including terbinafine (a squalene epoxidase inhibitor), do not. Educational objective: Congenital long QT syndrome is commonly caused by a mutation that slows the delayed rectifier potassium current that repolarizes the cardiomyocyte action potential. Certain medications (eg, macrolide antibiotics, antipsychotics, antiemetics) also slow the potassium repolarization current and prolong the QT interval. Excessive QT prolongation can trigger serious cardiac arrhythmia (ie, torsades de pointes), resulting in syncope or sudden cardiac death.

A 17-Year-Old Girl Is Brought to the Emergency Department After