Singer Wolfgang, Sandroni Paola, Opfer-Gehrking Tonette L, Suarez Guillermo A, Klein Caroline M, Hines Stacy, O'Brien Peter C, Slezak Jeffrey, Low Phillip A
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Arch Neurol. 2006 Apr;63(4):513-8. doi: 10.1001/archneur.63.4.noc50340. Epub 2006 Feb 13.
Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension. By enhancing ganglionic transmission, pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension.
To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide, alone or in combination with a subthreshold (2.5 mg) or suprathreshold (5 mg) dose of midodrine hydrochloride, compared with placebo.
We report a double-blind, randomized, 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH. A total of 58 patients with neurogenic OH were enrolled. After 1 day of baseline measurements, patients were given 4 treatments (3 active treatments [60 mg of pyridostigmine bromide; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride] and a placebo) in random order on successive days. Blood pressure (BP) and heart rate were measured, both supine and standing, immediately before treatment and hourly for 6 hours after the treatment was given.
No significant differences were seen in the supine BP, either systolic (P = .36) or diastolic (P = .85). In contrast, the primary end point of the fall in standing diastolic BP was significantly reduced (P = .02) with treatment. Pairwise comparison showed significant reduction by pyridostigmine alone (BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo; P = .04) and pyridostigmine and 5 mg of midodrine hydrochloride (BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo; P = .002). Standing BP improvement significantly regressed with improvement in OH symptoms.
Pyridostigmine significantly improves standing BP in patients with OH without worsening supine hypertension. The greatest effect is on diastolic BP, suggesting that the improvement is due to increased total peripheral resistance.
盐酸米多君是唯一一种在安慰剂对照治疗试验中被证明可改善直立性低血压（OH）的药物，但它会显著加重卧位高血压。通过增强神经节传递，溴吡斯的明有可能改善OH而不加重卧位高血压。
评估单剂量60毫克溴吡斯的明单独使用或与亚阈值剂量（2.5毫克）或超阈值剂量（5毫克）的盐酸米多君联合使用与安慰剂相比的疗效。
我们报告了一项关于溴吡斯的明治疗神经源性OH的双盲、随机、四路交叉研究。共纳入58例神经源性OH患者。在进行1天的基线测量后，患者在连续几天内随机接受4种治疗（3种活性治疗[60毫克溴吡斯的明；60毫克溴吡斯的明和2.5毫克盐酸米多君；60毫克溴吡斯的明和5毫克盐酸米多君]和一种安慰剂）。在治疗前立即测量仰卧位和站立位的血压（BP）和心率，并在给药后每小时测量1次，共测量6小时。
仰卧位收缩压（P = 0.36）或舒张压（P = 0.85）均无显著差异。相比之下，治疗后站立位舒张压下降的主要终点显著降低（P = 0.02）。两两比较显示，单独使用溴吡斯的明时显著降低（血压下降27.6毫米汞柱，而安慰剂为34.0毫米汞柱；P = 0.04），以及溴吡斯的明与5毫克盐酸米多君联合使用时显著降低（血压下降27.2毫米汞柱，而安慰剂为34.0毫米汞柱；P = 0.002）。站立位血压改善与OH症状改善显著相关。
溴吡斯的明可显著改善OH患者的站立位血压，而不加重卧位高血压。对舒张压的影响最大，表明这种改善是由于总外周阻力增加所致。
