Drugs For Hyperkeratotic Disorders

Keratolytic agents—including lactic acid, glycolic acid, salicylic acid, urea, and sulfur—are employed to treat various forms of hyperkeratosis ranging from calluses and verrucae to severe xerosis. Lactic and glycolic acid are a-hydroxy acids that are thought to disrupt ionic bonds and thus diminish corneocyte cohesion.

Salicylic acid is a ^-hydroxy acid that is thought to function through solubilization of intercellular cement, again reducing corneocyte adhesion. It appears to eliminate the stratum corneum layer by layer from the outermost level downward. This contrasts with the a-hydroxy acids, which preferentially diminish cellular cohesion between the corneocytes at the lowest levels of the stratum corneum.

Urea is an antimicrobial agent that denatures and dissolves proteins and increases skin absorption and retention of water. Sulfur is antiseptic, antiparasitic, antiseborrheic, and keratolytic, accounting for its myriad uses in dermatology.

Keratolytics are available in numerous formulations for treating skin diseases. Prolonged use of salicylic acid preparations over large areas, especially in children and patients with renal and hepatic impairment, can result in salicylism (see Chapter 26). Irritation is a common side effect with higher concentrations. Lactic acid (lac-hydrin, others) is an emollient that contains 12% lactic acid that is an effective moisturizer indicated for the treatment of xerosis and ichthyosis vulgaris.

Glycolic acid is marketed in multiple cosmetic preparations (4-10%) and is used for the treatment of xerosis, ichthyosis, and photoaging.

Destructive Agents

Podophyllin (podophyllum resin) is a mixture of chemicals from the plant Podophyllum peltatum (mandrake or May apple). The major constituent of the resin is podophyllotoxin (podofilox). It binds to microtubules and causes mitotic arrest in metaphase. Podophyllum resin (10-40%) is applied and left in place for 2-6 hours weekly for the treatment of anogenital warts. Irritation and ulcerative local reactions are the major side effects. It should not be used in the mouth or during pregnancy. Podofilox (condylox, others) is available as a 0.5% solution for application twice daily for 3 consecutive days. Weekly cycles may be repeated.

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