Shenfield G M
Drugs. 1982 Nov;24(5):414-39. doi: 10.2165/00003495-198224050-00004.
Bronchodilators may be classified into 3 groups: anticholinergics, beta-adrenoceptor agonists and methylxanthines. These drugs act through related biochemical pathways and there are theoretical reasons for expecting beneficial additive or synergistic interactions between them. While there is in vitro evidence of synergistic interactions producing bronchodilatation, in vivo studies indicate that the interactions are additive rather than synergistic but still of therapeutic value. There have been no clinical studies on methylxanthines combined with anticholinergic drugs, but there is an extensive and growing literature on the other combinations. The majority show clear evidence of an additive bronchodilator effect when anticholinergics are combined with beta 2-adrenoceptor agonists, although atropine sulphate is less effective in this regard than atropine methylnitrate or ipratropium bromide. This type of combination has only been tested by inhalation and, because of the slower onset of action of the anticholinergic group, it is preferable that the beta 2-adrenoceptor agonist be inhaled first. There is no evidence for an additive interaction of the side effects of these drugs. In general, bronchitics respond better than asthmatics to anticholinergic drugs. Studies on methylxanthines (usually theophylline) and adrenoceptor agonists may be divided into 2 groups: those using ephedrine and those using more selective beta-adrenoceptor agonists. Ephedrine is a relatively ineffective bronchodilator and often fails to add any useful bronchodilatation to theophylline. Also, there does seem to be a synergistic increase in side effects of the two drugs and this combination is therefore undesirable. Ephedrine has now been superseded by the more selective beta 2-adrenoceptor agonist drugs all of which, whether given orally, intravenously or by inhalation, appear to have an additive effect with the methylxanthines. It is often possible to achieve the same therapeutic effect with half doses of drugs from 2 different groups as with a full dose of 1 drug. This may sometimes, but not always, reduce side effects. There is evidence that giving 2 drugs by different routes is a useful therapeutic procedure; for example, the addition of an inhaled beta 2-adrenoceptor agonist may improve upon the maximal bronchodilatation achieved with intravenous theophylline. When theophylline is administered plasma levels of the drug should be monitored and it is possible that, when used in combination with a beta 2-adrenoceptor agonist, a therapeutic range lower than that normally recommended may apply. There is no longer any place for fixed combination bronchodilators and, in spite of recent suggestions, there is no evidence that bronchodilator combinations are responsible for an increase in asthma mortality. Further studies to clarify some aspects of bronchodilator combinations are needed. The therapeutic use of various combinations is briefly discussed.
支气管扩张剂可分为3类：抗胆碱能药物、β肾上腺素受体激动剂和甲基黄嘌呤类药物。这些药物通过相关的生化途径发挥作用，理论上它们之间可能存在有益的相加或协同相互作用。虽然体外有证据表明协同相互作用可产生支气管扩张作用，但体内研究表明这种相互作用是相加性的而非协同性的，但仍具有治疗价值。目前尚无关于甲基黄嘌呤类药物与抗胆碱能药物联合使用的临床研究，但关于其他联合用药的文献广泛且不断增加。大多数研究表明，抗胆碱能药物与β2肾上腺素受体激动剂联合使用时，有明显的相加性支气管扩张作用，尽管硫酸阿托品在这方面不如硝酸甲基阿托品或异丙托溴铵有效。这种联合用药仅通过吸入进行了测试，由于抗胆碱能药物起效较慢，最好先吸入β2肾上腺素受体激动剂。没有证据表明这些药物的副作用存在相加性相互作用。一般来说，慢性支气管炎患者对抗胆碱能药物的反应比哮喘患者更好。关于甲基黄嘌呤类药物（通常是茶碱）与肾上腺素受体激动剂的研究可分为两组：一组使用麻黄碱，另一组使用更具选择性的β肾上腺素受体激动剂。麻黄碱是一种相对无效的支气管扩张剂，通常不能给茶碱增加任何有用的支气管扩张作用。此外，这两种药物的副作用似乎确实有协同性增加，因此这种联合用药不可取。麻黄碱现已被更具选择性的β2肾上腺素受体激动剂药物所取代，所有这些药物，无论是口服、静脉注射还是吸入给药，似乎都与甲基黄嘌呤类药物有相加作用。通常用来自两个不同组的半量药物就能达到与全量一种药物相同的治疗效果。这有时（但并非总是）可以减少副作用。有证据表明，通过不同途径给予两种药物是一种有用的治疗方法；例如，添加吸入性β2肾上腺素受体激动剂可能会改善静脉注射茶碱所达到的最大支气管扩张效果。使用茶碱时，应监测药物的血浆水平，并且当与β2肾上腺素受体激动剂联合使用时，可能适用低于通常推荐的治疗范围。固定复方支气管扩张剂已不再适用，尽管最近有一些建议，但没有证据表明支气管扩张剂联合用药会导致哮喘死亡率增加。需要进一步的研究来阐明支气管扩张剂联合用药的某些方面。本文简要讨论了各种联合用药的治疗应用。
