- 著者
- Yukiko Yamazaki-Hashimoto Yuji Nakamura Hiroshi Ohara Xin Cao Ken Kitahara Hiroko Izumi-Nakaseko Kentaro Ando Hiroshi Yamazaki Takanori Ikeda Junichi Yamazaki Atsushi Sugiyama
- 出版者
- The Japanese Society of Toxicology
- 雑誌
- The Journal of Toxicological Sciences (ISSN:03881350)
- 巻号頁・発行日
- vol.40, no.1, pp.33-42, 2015-02-01 (Released:2014-12-18)
- 参考文献数
- 39
- 被引用文献数
- 9 11
Fluvoxamine is one of the typical selective serotonin-reuptake inhibitors. While its combined use with QT-prolonging drugs has been contraindicated because of the increase in plasma concentrations of such drugs, information is still limited whether fluvoxamine by itself may directly prolong the QT interval. We examined electropharmacological effects of fluvoxamine together with its pharmacokinetic profile by using the halothane-anesthetized dogs (n = 4). Fluvoxamine was intravenously administered in three escalating doses of 0.1, 1 and 10 mg/kg over 10 min with a pause of 20 min between the doses. The low dose provided therapeutic plasma drug concentration, whereas the middle and high doses attained approximately 10 and 100 times of the therapeutic ones, respectively. Supra-therapeutic concentration of fluvoxamine exerted the negative chronotropic, inotropic and hypotensive effects; and suppressed the atrioventricular nodal and intraventricular conductions, indicating inhibitory actions on Ca2+ and Na+ channels, whereas it delayed the repolarization in a reverse use-dependent manner, reflecting characteristics of rapidly activating delayed rectifier K+ current channel-blocking property. Fluvoxamine prolonged the terminal repolarization phase at 100 times higher concentration than the therapeutic, indicating its proarrhythmic potential. Thus, fluvoxamine by itself has potential to directly induce long QT syndrome at supra-therapeutic concentrations.
- 著者
- Tadashi Fujino Yukiko Yamazaki Takaya Tsubota Takanori Ikeda
- 出版者
- 一般社団法人 インターナショナル・ハート・ジャーナル刊行会
- 雑誌
- International Heart Journal (ISSN:13492365)
- 巻号頁・発行日
- vol.56, no.4, pp.459-461, 2015 (Released:2015-07-13)
- 参考文献数
- 10
A 67-year-old man who had cardiopulmonary arrest (CPA) at home was admitted to our institution. His spontaneous circulation was restored by bystander cardiopulmonary resuscitation (CPR) performed by his wife and an automated external defibrillator (AED). J waves were observed in the inferior leads of an electrocardiogram. We performed an implantable cardioverter defibrillator (ICD) implantation. After the ICD implantation, appropriate shocks due to ventricular fibrillation (VF) were observed on interrogation of the ICD at a frequency of twice a month. Most VF events occurred in the early morning between 1:00 to 6:00, and ventricular premature contractions (VPCs) were detected just before the occurrence of VF. Since the VF events always occurred in the early morning, we started long-acting disopyramide (150 mg/day, before bedtime), which has a muscarinic receptor blocking action. As a result, he has not received any appropriate ICD shocks for more than two years.