Jackson L D, Polygenis D, McIvor R A, Worthington I
Department of Pharmacy, Sunnybrook Health Science Centre, Toronto, Ontario.
Can J Clin Pharmacol. 1999 Spring;6(1):26-37.
Current guidelines emphasize the efficacy of inhaled corticosteroids for anti-inflammatory activity in asthma, and recommend higher doses and earlier initiation of therapy than previous guidelines. Concern over possible side effects with long term use has prompted an evaluation of the available literature to determine the optimal dose that may be administered without fear that significant side effects might occur (e.g., growth retardation in children, adrenal suppression, reduction in bone mineral density, cataract formation). Regular treatment with the following drugs in adults and children, respectively, is unlikely to result in any clinically significant effects on the above parameters: beclomethasone dipropionate less than 1500 micrograms and 400 micrograms, budesonide less than 1600 micrograms and 400 micrograms, flunisolide less than 2000 micrograms and 1000 micrograms, fluticasone propionate approximately 500 micrograms and 200 micrograms, and triamcinolone acetonide less than 1600 micrograms and 1200 micrograms. Systemic effects are influenced by potency and bioavailability. Inhaled corticosteroids owe their favourable safety profile to a high topical to systemic potency ratio compared with that of oral corticosteroids. In terms of relative topical potency, fluticasone propionate is more potent than budesonide, which is more potent than beclomethasone dipropionate, which is more potent than flunisolide and triamcinolone acetonide. The delivery device has an important influence on the amount of drug reaching the patient. A spacer device attached to a metered dose inhaler or a Turbuhaler reduces oropharyngeal deposition and increases lung deposition. As a result, a dosage reduction may be possible, and local side effects of dysphonia and oral candidiasis may be reduced. Patients requiring continued high doses by the inhaled route should be monitored for systemic effects and be considered for osteoporosis prevention therapy if appropriate.
当前指南强调吸入性糖皮质激素在哮喘抗炎治疗中的疗效，且与以往指南相比，推荐更高剂量并更早开始治疗。对长期使用可能产生的副作用的担忧促使人们对现有文献进行评估，以确定在不用担心出现显著副作用（如儿童生长发育迟缓、肾上腺抑制、骨矿物质密度降低、白内障形成）的情况下可使用的最佳剂量。分别对成人和儿童使用以下药物进行常规治疗，不太可能对上述参数产生任何具有临床意义的影响：二丙酸倍氯米松低于1500微克和400微克、布地奈德低于1600微克和400微克、氟尼缩松低于2000微克和1000微克、丙酸氟替卡松约500微克和200微克、曲安奈德低于1600微克和1200微克。全身效应受药物效力和生物利用度的影响。与口服糖皮质激素相比，吸入性糖皮质激素因其高局部与全身效力比而具有良好的安全性。就相对局部效力而言，丙酸氟替卡松比布地奈德更有效，布地奈德比二丙酸倍氯米松更有效，二丙酸倍氯米松比氟尼缩松和曲安奈德更有效。给药装置对到达患者体内的药物量有重要影响。连接到定量吸入器或都保的储雾罐可减少口咽部药物沉积并增加肺部药物沉积。因此，可能可以减少剂量，并且可以减少声音嘶哑和口腔念珠菌病等局部副作用。需要通过吸入途径持续高剂量用药的患者应监测全身效应，并在适当时考虑进行骨质疏松症预防治疗。
