Serial plasma and urine measurements of a patient with acute intoxication of zolpidem and flunitrazepam resulting in QT prolongation and ventricular tachycardia

Ahn, Hong Joon; Jeong, Wonjoon; Kim, Kwan Jae; Kim, Sun Cheun; Kim, Dong Woo; Chang, Hye Jin; Kang, Changshin; Oh, Se Kwang; Cho, Sung Uk; Min, Jin Hong; Cho, Yong Chul; Park, Jung Soo; Ryu, Seung Ho; You, Yeon Ho; Lee, Jing Woong; Kim, Min Su

doi:10.1080/15563650.2019.1663206

Cited by 6 publications

(2 citation statements)

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“…Arrhythmia is also a side effect of zolpidem, but rarely reported. There have been reports of zolpidem causing QT prolongation and provoking ventricular brillation [7,8]. However, atrial brillation (AF) as a side effect of zolpidem use has not been reported yet.…”

Section: Introductionmentioning

confidence: 99%

Zolpidem-triggered atrial fibrillation in a patient with cardiomyopathy: a case report

Li,

Jin

2023

Preprint

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Background: Zolpidem is a non-benzodiazepine hypnotics widely used to manage insomnia. Zolpidem-triggered atrial fibrillation (AF) in patients with cardiomyopathy has never been reported before. Case presentation: A 40-year-old man with Duchenne muscular dystrophy-related cardiomyopathy attempted suicide and developed new-onset AF after zolpidem overdose. One year before admission, the patient visited our clinic due to chest discomfort and fatigue after daily walks for 1 month; both electrocardiography (ECG) and 24-hour Holter ECG results did not detect AF. After administration of cardiac medication (digoxin 0.125 mg/day, spironolactone 40 mg/day, furosemide 20 mg/day, bisoprolol 5 mg/day, sacubitril valsartan sodium tablets 25 mg/day), he felt better. AF had never been observed before this admission via continuous monitoring during follow-up. Sixteen days before admission, the patient saw a sleep specialist and started on zolpidem tartrate tablets (10 mg/day) due to insomnia for 6 months; ECG results revealed no obvious change. The night before admission, the patient attempted suicide by overdose with 40 mg of zolpidem after an argument, which resulted in severe lethargy. At admission, his ECG revealed new-onset AF, so zolpidem was stopped immediately. 9 hours into admission, AFspontaneously terminated into normal sinus rhythm. Results from the ECG on the following days and the 24-hour Holter ECG at 1-month follow-up showed that no AF was detected. Conclusions: Zolpidem is a frequent first choice of medication for insomnia. However, this case suggests zolpidem overdose could increase the risk of AF in patients with cardiomyopathy. Zolpidem could have caused AF via respiratory depression, which leads to acute atrial distension and hypercapnia. These acute transient arrhythmogenic changes during zolpidem overdose can increase vulnerability to AF in patient with pre-existing cardiomyopathy. Thus, the heart rhythm should be monitored when zolpidem is prescribed in patients with cardiomyopathy.

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Section: Introductionmentioning

confidence: 99%

Zolpidem-triggered atrial fibrillation in a patient with cardiomyopathy: a case report

Li,

Jin

2023

Preprint

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“…Tramadol and zolpidem are well-known analgesics and hypnotics widely used to treat pain or insomnia. Recently, cardiac safety concerns regarding administration of zolpidem have been raised by a case of long QT syndrome complicated by torsade de pointes tachyarrhythmia [1]. QT prolongation is a wellknown complication that occurs when tramadol is ingested in large amounts acutely.…”

Section: Introductionmentioning

confidence: 99%

Serial Blood and Urine Drug Concentration Measurement in a Patient Withacute Intoxication Bytramadoland Zolpidem Resulting in Qt Prolongation: Case Report

Lee

Park

Kim

et al. 2020

Preprint

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Background: QT prolongation is a well-known complication when tramadol or zolpidem is ingested in large amounts acutely. However, the blood drug concentration resulting in QT prolongation or tachyarrhythmia when tramadol and zolpidem are ingested simultaneously in large amounts has not yet been reported. We report a case of acute intoxication by tramadol and zolpidem resulting in QT prolongation in a patient in whomserial blood and urine tramadol and zolpidemconcentrationswere determined.Case presentation:A 38-year-old male patient presented tothe emergency medical centrebecause ofpoisoning from 3 g of tramadol and 50 mg of zolpidemat 3 h before hisemergency department(ED) visit.During supportive treatment, he developed QT prolongation without clinical manifestations. He was discharged five days after admission without any sequelae. We measured the blood and urine concentrations of tramadol and zolpidemat various time points, which revealed ablood tramadol concentration-dependent change in QTc intervals and increasing blood tramadol concentration at 8 h after the ED visit,with a sustainedlow zolpidem concentration.Tramadol and zolpidem are metabolized by the same enzyme, cytochrome P450 3A4.Therefore, competitive inhibition bya P450 3A4isoenzyme may lead to increases indrugtoxicity. The QT interval in patients acutely intoxicated bytramadol should be evaluated carefully, particularlywhen tramadol is co-ingested with other drugs.Conclusions:Considering the half-life of tramadolor zolpidem and potential for continued absorption of drugs remaining in the gastrointestinal tract, it is necessary to observe patients viacardiac monitoring for more than 36 hafteracute intoxication.The blood concentration of tramadol may increaseand result in QT prolongationeven afterappropriate initial treatment.

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Potentiation of the depressant effect of alcohol by flunitrazepam in rats: an electrocorticographic, respiratory and electrocardiographic study

Freitas,

Amaral,

Conceição

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Serial plasma and urine measurements of a patient with acute intoxication of zolpidem and flunitrazepam resulting in QT prolongation and ventricular tachycardia

Cited by 6 publications

References 4 publications

Zolpidem-triggered atrial fibrillation in a patient with cardiomyopathy: a case report

Zolpidem-triggered atrial fibrillation in a patient with cardiomyopathy: a case report

Serial Blood and Urine Drug Concentration Measurement in a Patient Withacute Intoxication Bytramadoland Zolpidem Resulting in Qt Prolongation: Case Report

Potentiation of the depressant effect of alcohol by flunitrazepam in rats: an electrocorticographic, respiratory and electrocardiographic study

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