Dermatological Pharmacology The Structure And Function Of Skin

A unique aspect of dermatological pharmacology is the direct accessibility of the skin as a target organ for diagnosis and treatment (Figure 62-1). The skin acts as a two-way barrier to prevent absorption or loss of water and electrolytes. The barrier resides in the outermost layer of the epidermis, the stratum corneum, as evidenced by approximately equal rates of penetration of chemicals through isolated stratum corneum or whole skin. Having lost their nuclei and cytoplasmic organelles, the corneocytes of the stratum corneum are nonviable. The cells are flattened, and the fibrous keratins are aligned into disulfide cross-linked macrofibers in association with filaggrin, the major protein component of the keratohyalin granule. Each cell develops a cornified envelope resulting from cross-linking of involucrin and keratohyalin, forming an insoluble exoskeleton that acts as a rigid scaffold for the internal keratin filaments. The intercellular spaces are filled with hydrophobic lamellar lipids derived from membrane-coating granules. The combination of hydro-philic cornified cells in hydrophobic intercellular material provides a barrier to both hydrophilic and hydrophobic substances. In dermatological diseases, the thickened epidermis may further diminish the penetration of pharmacological agents into the dermis.


Appropriate use of topical agents requires an appreciation of the factors that influence percutaneous absorption (see Chapter 1). Molecules can penetrate the skin by three routes: through intact stratum corneum, through sweat ducts, or through the sebaceous follicle. The surface of the stratum corneum presents more than 99% of the total skin surface available for percutaneous drug absorption. Passage through this outermost layer is the rate-limiting step for percutaneous absorption. The major steps involved in percutaneous absorption include the establishment of a concentration gradient, which provides the driving force for drug movement across the skin; release of drug from the vehicle (partition coefficient); and drug diffusion across the layers of the skin (diffusion coefficient). Preferable characteristics of topical drugs include low molecular mass (600 Da), adequate solubility in oil and water, and a high partition coefficient. Except for very small particles, water-soluble ions and polar molecules do not penetrate intact stratum corneum.


The viable epidermis contains a variety of enzyme systems capable of metabolizing drugs that reach this compartment, including CYPs, epoxide hydrolase, transferases such as N-acetyl-trans-ferases, and diverse enzymes including glucuronyl transferases and sulfatases. Transporter proteins that influence influx (OATP) or efflux (MDR and LRD) of certain xenobiotics are present in human keratinocytes. While substrate turnover is considerably less than that for hepatic CYPs, these enzymes influence concentrations of xenobiotics in the skin.

General Guidelines for Topical Therapy altered barrier function In many dermatological diseases, such as psoriasis, the stratum corneum is abnormal, and barrier function is compromised. In these settings, percutaneous absorption may be increased to the point that standard drug doses can result in systemic toxicity (e.g., hypothalamic-pituitary-adrenal axis suppression can result from systemic absorption of potent topical glucocorticoids).

hydration Drug absorption is increased with hydration. Methods of hydration include occlusion with an impermeable film, application of lipophilic occlusive vehicles such as ointments, and soaking dry skin before occlusion.

11 Habits To Make or Break For Soft Flawless Skin

11 Habits To Make or Break For Soft Flawless Skin

Habits to Break and Habits to Maintain for Dazzling Skin. As you all know, our skin is the obvious appearance of who or what we are, or perhaps would like to be. However, it is more than just a simple mask.

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