Foley J E, Sigurdson M J, Conliffe T F, Fand R S, Anthonisen N R
Clin Pharmacol Ther. 1982 Aug;32(2):149-55. doi: 10.1038/clpt.1982.140.
After a 7-day lead-in period, one of three beta-adrenergic antagomists was taken for 2 wk by 10 healthy male subjects. The drugs were metoprolol (cardioselective) and propranolol and nadolol (both nonselective). Dosage was according to currently recommended regimens and was increased after the first week (50 to100 mg b.i.d., 20 to 40 mg q.i.d., and 80 to 160 mg q.d.). Pulmonary mechanics and density dependence (DD) of maximal expiratory flow were measured before and at the end of the placebo lead-in period and the low- and high-dose treatment weeks. Total lung capacity (TLC), residual volume (RV), and RV/TLC all rose (P less than 0.05) after high-dose nadolol. Forced vital capacity (FVC) and expiratory reserve volume fell (P less than 0.05) after high-dose nadolol. Forced vital capacity (FVC) and expiratory reserve volume fell (P less than 0.05) after high-dose metoprolol. There was no change in forced expiratory volume in 1.0 sec (FEV1), FEV1/FVC, maximal midexpiratory flow rate, or airway resistance with any of the beta-antagonists. Decreases (P less than 0.05) in maximal expiratory flow determined at 50% of the vital capacity occurred after propranolol and metoprolol, but not after nadolol. A dose-related decrease in DD at 50% of the vital capacity accompanied nadolol dosing, but was significant only after the high-dose regimen. The decreases in DD with nadolol, as well as its effect on RV/TLC, are consistent with small airway narrowing. The findings with metoprolol and propranolol suggest that they affect central as well as peripheral airways.
在为期7天的导入期后,10名健康男性受试者服用三种β-肾上腺素能拮抗剂之一,为期2周。药物分别为美托洛尔(心脏选择性)、普萘洛尔和纳多洛尔(均为非选择性)。剂量按照当前推荐方案给药,并在第一周后增加(美托洛尔50至100mg,每日两次;普萘洛尔20至40mg,每日四次;纳多洛尔80至160mg,每日一次)。在安慰剂导入期结束时以及低剂量和高剂量治疗周结束时,测量肺力学和最大呼气流量的密度依赖性(DD)。高剂量纳多洛尔治疗后,肺总量(TLC)、残气量(RV)和RV/TLC均升高(P<0.05)。高剂量纳多洛尔治疗后,用力肺活量(FVC)和呼气储备量下降(P<0.05)。高剂量美托洛尔治疗后,用力肺活量(FVC)和呼气储备量下降(P<0.05)。使用任何一种β受体拮抗剂后,1秒用力呼气量(FEV1)、FEV1/FVC、最大呼气中期流速或气道阻力均无变化。普萘洛尔和美托洛尔治疗后,在肺活量50%时测定的最大呼气流量降低(P<0.05),但纳多洛尔治疗后未出现这种情况。纳多洛尔给药后,肺活量50%时的DD呈剂量相关下降,但仅在高剂量方案后具有统计学意义。纳多洛尔导致的DD下降及其对RV/TLC的影响与小气道狭窄一致。美托洛尔和普萘洛尔的研究结果表明,它们对中央气道和外周气道均有影响。