Adverse reactions of externally applied drugs and inert substances.

The lack of a first-pass effect for locally-applied substances is often not considered. This is especially true for such central nervous system agents as salicylic acid, hexachlorophene or caffeine which have a relatively low toxicity when applied orally. Manifestation of dermal irritation, such as a beginning rash or inflammation, are often tolerated because the beneficial effects of some topically applied substances outweight the damage (Dithranol, 5-Fluorouracil). This applies to some anti-phlogistics as well, which may also cause skin irritation. Some substances, such as benzoyl peroxide, vitamin-A acid and beta-estradiol have direct or indirect desiccative effects so that skin irritations may occur. Other substances, such as tar, for example, are applied locally although they may have a carcinogenic potential when misused, or when contraindications for its use are disregarded. Local risks can be recognized in clinical-experimental and clinical testing of dermatological products. One must, however, look carefully for an intensification of possible risks related to the method of application, the condition of the skin, the site of application, supporting therapeutic measures or changes in the composition of the vehicle. Lanolin, cetyl alcohol and myristyl alcohol, sorbitol, isopropyl-myristate as well as polyethylene glycols (PEG) penetrate the skin like active substances. Some have been connected with skin allergies. In addition, some preservatives have mutagenic properties. Many vehicles cause dehydration of the horny layer and thus result in chronic surface damage. This is true for hygroscopic substances such as PEG as well as for liquid paraffins, lipid solvents (alcohol, acetone), solvents such as propylene glycol and for some O/W emulsifiers.