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A 22-year-old woman presents with a complaint of worsening psoriasis. She has a strong family history of the disease and has had lesions on her scalp and elbows for several years. She recently noted new lesions developing on her knees and the soles of her feet. She has been using topical over-the-counter hydrocortisone cream but admits that this treatment does not seem to help. What therapeutic options are available for the treatment of this chronic disease?

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Diseases of the skin offer special opportunities to the clinician. In particular, the topical administration route is especially appropriate for skin diseases, although some dermatologic diseases respond as well or better to drugs administered systemically.

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The general pharmacokinetic principles governing the use of drugs applied to the skin are the same as those involved in other routes of administration (see Chapters 1 and 3). Although often depicted as a simple three-layered structure (Figure 61–1), human skin is a complex series of diffusion barriers. Quantitation of the flux of drugs and drug vehicles through these barriers is the basis for pharmacokinetic analysis of dermatologic therapy, and techniques for making such measurements are rapidly increasing in number and sensitivity.

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Figure 61–1
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Schematic diagram of percutaneous absorption. (Redrawn from Orkin M, Maibach HI, Dahl MV: Dermatology. Appleton & Lange, 1991.)

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Major variables that determine pharmacologic response to drugs applied to the skin include the following:

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  1. Regional variation in drug penetration: For example, the scrotum, face, axilla, and scalp are far more permeable than the forearm and may require less drug for equivalent effect.

  2. Concentration gradient: Increasing the concentration gradient increases the mass of drug transferred per unit time, just as in the case of diffusion across other barriers (see Chapter 1). Thus, resistance to topical corticosteroids can sometimes be overcome by use of higher concentrations of drug.

  3. Dosing schedule: Because of its physical properties, the skin acts as a reservoir for many drugs. As a result, the "local half-life" may be long enough to permit once-daily application of drugs with short systemic half-lives. For example, once-daily application of corticosteroids appears to be just as effective as multiple applications in many conditions.

  4. Vehicles and occlusion: An appropriate vehicle maximizes the ability of the drug to penetrate the outer layers of the skin. In addition, through their physical properties (moistening or drying effects), vehicles may themselves have important therapeutic effects. Occlusion (application of a plastic wrap to hold the drug and its vehicle in close contact with the skin) is extremely effective in maximizing efficacy.

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The skin reacts to many systemic medications with a variety of symptom-generating responses. In addition, some dermatologic medications themselves cause skin reactions. The major types of reactions are summarized in Table 61–1.

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Table 61–1 Local Cutaneous Reactions to ...

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