Wake Forest Institute for Regenerative Medicine,Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, USA.
Br J Clin Pharmacol. 2011 Aug;72(2):186-96. doi: 10.1111/j.1365-2125.2010.03813.x.
Antimuscarinic agents are the main drugs used to treat patients with the overactive bladder (OAB) syndrome, defined as urgency, with or without urgency incontinence, usually with increased daytime frequency and nocturia. Since the treatment is not curative and since OAB is a chronic disease, treatment may be life-long. Antimuscarinics are generally considered to be ‘safe’ drugs, but among the more serious concerns related to their use is the risk of cardiac adverse effects, particularly increases in heart rate (HR) and QT prolongation and induction of polymorphic ventricular tachycardia (torsade de pointes). An elevated resting HR has been linked to overall increased morbidity and mortality, particularly in patients with cardiovascular diseases. QT prolongation and its consequences are not related to blockade of muscarinic receptors, but rather linked to inhibition of the hERG potassium channel in the heart. However, experience with terodiline, an antimuscarinic drug causing torsade de pointes in patients, has placed the whole drug class under scrutiny. The potential of the different antimuscarinic agents to increase HR and/or prolong the QT time has not been extensively explored for all agents in clinical use. Differences between drugs cannot be excluded, but risk assessments based on available evidence are not possible.
抗毒蕈碱药物是治疗膀胱过度活动症(OAB)患者的主要药物,其定义为尿急,伴有或不伴有急迫性尿失禁,通常伴有日间尿频和夜尿增多。由于治疗不能治愈,并且 OAB 是一种慢性疾病,因此治疗可能是终身的。抗毒蕈碱药物通常被认为是“安全”的药物,但与它们的使用相关的更严重的问题之一是心脏不良事件的风险,特别是心率(HR)增加、QT 延长和诱发多形性室性心动过速(尖端扭转型室性心动过速)。静息心率升高与总发病率和死亡率增加有关,特别是在心血管疾病患者中。QT 延长及其后果与毒蕈碱受体的阻断无关,而是与心脏 hERG 钾通道的抑制有关。然而,曲司氯铵(一种引起尖端扭转型室性心动过速的抗毒蕈碱药物)的经验使整个药物类别受到审查。在临床使用的所有药物中,尚未广泛探索不同的抗毒蕈碱药物增加 HR 和/或延长 QT 时间的潜力。不能排除药物之间的差异,但基于现有证据进行风险评估是不可能的。