Shibao Cyndya, Raj Satish R, Gamboa Alfredo, Diedrich André, Choi Leena, Black Bonnie K, Robertson David, Biaggioni Italo
Department of Medicine, Division of Clinical Pharmacology, and the Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, TN 37212, USA.
Hypertension. 2007 Jul;50(1):47-53. doi: 10.1161/HYPERTENSIONAHA.107.089961. Epub 2007 May 21.
Atomoxetine, a selective norepinephrine transporter blocker, could increase blood pressure by elevating norepinephrine concentration in peripheral sympathetic neurons. This effect may be masked in healthy subjects by central sympatholytic mechanisms. To test this hypothesis we studied the pressor effect of 18 mg of atomoxetine (pediatric dose) in 21 patients with damage of the central (10 subjects) and peripheral (11 subjects) autonomic nervous system. Atomoxetine was administered in a randomized, crossover, placebo-controlled fashion, and blood pressure and heart rate were measured at baseline and for 60 minutes after drug intake. Atomoxetine acutely increased seated and standing systolic blood pressure in patients with central autonomic failure by 54+/-26 (mean+/-standard deviation; P=0.004) and 45+/-23 mm Hg (P=0.016), respectively, as compared with placebo. At the end of the observation period the mean seated systolic blood pressure in the atomoxetine group was in the hypertensive range (149+/-26, range 113 to 209 mm Hg). However, in patients with peripheral autonomic failure, atomoxetine did not elicit a pressor response; seated and standing systolic blood pressure increased by 4+/-18 mm Hg (P=0.695) and 0.6+/-8 mm Hg (P=0.546) with atomoxetine as compared with placebo. In conclusion, atomoxetine induces a dramatic increase in blood pressure in patients with central autonomic failure even at very low doses. These findings suggest that a functional central sympatholytic pathway is essential to avoid hypertension in patients treated with this drug. Caution should be exercised when this medication is used in patients with milder form of autonomic impairment.
托莫西汀是一种选择性去甲肾上腺素转运体阻滞剂，可通过提高外周交感神经元中的去甲肾上腺素浓度来升高血压。在健康受试者中，这种效应可能会被中枢性抗交感神经机制所掩盖。为了验证这一假设，我们研究了18毫克托莫西汀（儿童剂量）对21例中枢（10例受试者）和外周（11例受试者）自主神经系统受损患者的升压作用。托莫西汀采用随机、交叉、安慰剂对照的方式给药，并在基线以及服药后60分钟测量血压和心率。与安慰剂相比，托莫西汀使中枢自主神经功能衰竭患者的坐位和站立位收缩压分别急剧升高54±26（平均值±标准差；P = 0.004）和45±23毫米汞柱（P = 0.016）。在观察期结束时，托莫西汀组的平均坐位收缩压处于高血压范围（149±26，范围为113至209毫米汞柱）。然而，在外周自主神经功能衰竭患者中，托莫西汀未引起升压反应；与安慰剂相比，托莫西汀使坐位和站立位收缩压分别升高4±18毫米汞柱（P = 0.695）和0.6±8毫米汞柱（P = 0.546）。总之，即使在非常低的剂量下，托莫西汀也会使中枢自主神经功能衰竭患者的血压急剧升高。这些发现表明，功能性中枢抗交感神经通路对于避免使用该药物治疗的患者发生高血压至关重要。在患有较轻形式自主神经功能损害的患者中使用这种药物时应谨慎。
