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figure 62-1 Skin as a pharmacological target. The skin is a multicellular organ containing numerous indigenous cells and structures as well as circulating cells that are potential targets for pharmacological intervention (black arrows). UVB, ultraviolet radiation (290-320 nm); PUVA, psoralen activated by UVA radiation (320-400 nm).

figure 62-1 Skin as a pharmacological target. The skin is a multicellular organ containing numerous indigenous cells and structures as well as circulating cells that are potential targets for pharmacological intervention (black arrows). UVB, ultraviolet radiation (290-320 nm); PUVA, psoralen activated by UVA radiation (320-400 nm).

vehicle Most topical medications are incorporated into bases or vehicles that are applied directly to the skin. The chosen vehicle can influence drug absorption and provide therapeutic efficacy; for example, an ointment is more occlusive and has superior emollient properties than a cream or a lotion base.

Newer vehicles include liposomes and microgel formulations. Liposomes are concentric spherical shells of phospholipids in an aqueous medium that may enhance percutaneous absorption. Variations in size, charge, and lipid content can influence liposome function substantially. Liposomes penetrate compromised epidermal barriers more efficiently. Microgels are polymers that may enhance solubilization of certain drugs, thereby enhancing penetration and diminishing irritancy.

Transfersomes are a drug-delivery technology based on highly deformable, ultraflexible lipid vesicles that penetrate the skin when applied nonocclusively. Finally, pressure waves generated by intense laser radiation can permeabilize the stratum corneum and may provide a novel system for transdermal drug delivery.

Children have a greater ratio of surface area to mass than adults, so a given amount of topical drug results in a greater systemic dose. Based on transepidermal water loss and percutaneous absorption studies, term infants seem to possess a stratum corneum with barrier properties comparable with adults.

Application Frequency

For certain drugs, once-daily application of a larger dose may be as effective as more frequent applications of smaller doses. The stratum corneum may act as a drug reservoir that allows gradual penetration into the viable skin layers over a prolonged period. Intermittent pulse therapy— treatment for several days or weeks alternating with treatment-free periods—may prevent development of tachyphylaxis associated with drugs such as topical glucocorticoids.

Intralesional Administration

Intralesional drug administration is used mainly for inflammatory lesions but also can be used for treatment of warts and selected neoplasms. Medications injected intralesionally have the advantages of direct contact with the underlying pathologic process, no first-pass metabolism, and the formation of a slowly absorbed depot of drug. In considering the use of intralesional medications, it is important to be cognizant of the possibility of systemic absorption of the medication.

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