Jansen W, Meyer L, Tauchert M
Medizinische Klinik 1 Kardiologie, Städtisches Krankenhaus, Leverkusen, Federal Republic of Germany.
Am J Cardiol. 1988 Mar 25;61(9):31E-35E. doi: 10.1016/0002-9149(88)90087-2.
The optimal dose of nitrates is still controversial, as chronic usage of too high a dose may result in a decrease in vascular response. The dose should be determined to reduce preload acutely, and not to decrease the activity during chronic therapy. To determine this dose, 50 patients with angiographically confirmed coronary artery disease were studied. The effects on heart rate and mean systemic and pulmonary arterial pressures at rest and during exercise, and work capacity and duration were measured. The patients were classified into 5 groups, receiving placebo or isosorbide-5-mononitrate, 5, 10, 20 and 50 mg, respectively, as a single oral dose. Placebo had no effect on the measured parameters. All doses of isosorbide-5-mononitrate reduced mean pulmonary arterial pressure: 10 mg--by 16% at rest and 24% during exercise; 20 mg--24% and 34%, respectively (a near maximal effect); and 50 mg--27% and 38%. Similar results were found also for work capacity: 10 mg increased work capacity by 33%; 20 mg--79%; and 50 mg--56%. Thus, the therapeutically optimal single dose is about 20 mg. Higher doses produce no additional benefit and increase the risk for tolerance development.
硝酸盐的最佳剂量仍存在争议，因为长期使用过高剂量可能会导致血管反应降低。剂量的确定应旨在急性降低前负荷，而非在长期治疗期间降低活性。为确定该剂量，对50例经血管造影证实患有冠状动脉疾病的患者进行了研究。测量了静息和运动期间对心率、平均体循环和肺动脉压的影响以及工作能力和持续时间。患者被分为5组，分别接受安慰剂或单硝酸异山梨酯，单次口服剂量分别为5、10、20和50毫克。安慰剂对所测参数无影响。所有剂量的单硝酸异山梨酯均降低了平均肺动脉压：10毫克——静息时降低16%，运动时降低24%；20毫克——分别降低24%和34%（接近最大效应）；50毫克——降低27%和38%。工作能力方面也发现了类似结果：10毫克使工作能力提高33%；20毫克——提高79%；50毫克——提高56%。因此，治疗的最佳单次剂量约为20毫克。更高剂量不会带来额外益处，反而会增加耐受性发展的风险。
