Goa K L
ADIS Drug Information Service, Auckland, New Zealand.
Drugs. 1988;36 Suppl 5:51-61. doi: 10.2165/00003495-198800365-00011.
The development of topical corticosteroids since the 1950s has opened new doors for dermatologists previously faced with treating intractable dermatoses, so that the pharmacology of topically applied corticosteroids is now reasonably well described. Manipulation of the steroid molecule has produced compounds with greater lipophilicity, fewer mineralocorticoid properties and high potency. Potency is determined through various techniques, notably the vasoconstrictor assay as well as the mitotic index suppression method and atrophogenic potential assay. The mechanism of activity of corticosteroids is thought to result, at least in part, from binding of the drug to steroid receptors, with resultant effects on the synthesis of proteins responsible for specific effects. Corticosteroids are proposed to alter the inflammatory response, and thus provide therapeutic benefits, via actions on mediator release and function, inflammatory cell function and release of lysosomal enzymes. Disadvantages of corticosteroid activity include the possibility of adrenal suppression, epidermal and dermal thinning, and local effects such as purpura, striae, and steroid-induced rosacea and perioral dermatitis. The cutaneous pharmacokinetics, particularly of absorption of topical corticosteroids, must be examined in parallel with their pharmacodynamic effects to gain a more complete understanding of activity. Many factors can affect percutaneous steroid absorption: drug lipophilicity and solubility, drug concentration, anatomical site, age of the patient, presence of skin disease and use of occlusive dressings will each influence the degree to which topically applied corticosteroids achieve their intended therapeutic results. Cutaneous metabolism is a poorly understood process at present, but one which is acknowledged to have some impact on the biotransformation of corticosteroids applied topically. Thus, although some gaps still persist in present knowledge of the pharmacology and pharmacokinetics of this important class of drugs, there can be no denying the contribution of topical corticosteroids to the therapy of dermatoses.
自20世纪50年代以来，局部用皮质类固醇的发展为以前面临治疗顽固性皮肤病的皮肤科医生打开了新的大门，因此现在对局部应用皮质类固醇的药理学已有相当充分的描述。对类固醇分子的操控产生了亲脂性更强、盐皮质激素特性更少且效力更高的化合物。效力通过各种技术来确定，尤其是血管收缩试验以及有丝分裂指数抑制法和致萎缩潜力试验。皮质类固醇的活性机制被认为至少部分是由于药物与类固醇受体结合，从而对负责特定效应的蛋白质合成产生影响。有人提出皮质类固醇通过对介质释放和功能、炎症细胞功能以及溶酶体酶释放的作用来改变炎症反应，从而提供治疗益处。皮质类固醇活性的缺点包括肾上腺抑制、表皮和真皮变薄的可能性，以及紫癜、萎缩纹和类固醇性酒渣鼻及口周皮炎等局部效应。必须将皮肤药代动力学，尤其是局部用皮质类固醇的吸收情况，与其药效学效应一并进行研究，以便更全面地了解其活性。许多因素会影响经皮类固醇吸收：药物的亲脂性和溶解性、药物浓度、解剖部位、患者年龄、皮肤病的存在以及闭塞性敷料的使用，都会影响局部应用皮质类固醇达到预期治疗效果的程度。皮肤代谢目前是一个了解甚少的过程，但人们承认它对局部应用的皮质类固醇的生物转化有一定影响。因此，尽管目前对这类重要药物的药理学和药代动力学的认识仍存在一些空白，但不可否认局部用皮质类固醇对皮肤病治疗的贡献。
