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Pharmacology: Mechanism of Action: Betamethasone: Corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin) and stimulate transcription of messenger RNA (messenger RNA); and subsequent protein synthesis of various inhibitory enzymes responsible for the anti-inflammatory effects which include inhibition of early processes eg, edema, fibrin deposition, capillary dilatation movement of phagocytes into the area and phagocytic activities. Later processes eg, capillary production, collagen disposition and keloid formation also are inhibited by corticosteroids. The overall actions of topical corticosteroids are catabolic.
Factors that increase the clinical efficacy and potential for adverse effects of topical corticosteroids include enhancement of pharmacologic activity of the compound by altering molecular structure, increasing stratum corneum penetration of the compound, and increasing bioavailability of the compound from the vehicle.
The pharmacologic activity of topical corticosteroids is increased by several changes in molecular structure. Addition of 9-alpha-fluorine atom increases the anti-inflammatory glucocorticoid activity, but simultaneously increases undesired mineralocorticoid activity. Mineralocorticoid activity is diminished by addition of a 16-hydroxy group with longer side chains such as acetonide, propionate, or valerate increases lipophilicity and subsequently stratum corneum penetration.
Neomycin: Actively transported across the bacterial cell membrane, binds to a specific receptor protein on the 30S subunit of bacterial ribosomes and interferes with an initiation complex between mRNA (messenger RNA) and the 30S subunit, inhibiting protein synthesis. DNA may be misread, thus producing nonfunctional proteins; polyribosomes are split apart and are unable to synthesize protein.
Note: Aminoglycosides are bactericidal, while most other antibiotics that interfere with protein synthesis are bacteriostatic.
Pharmacokinetics: Absorption: Betamethasone: Absorbed systemically across the stratum corneum and penetration is primarily enhanced by increasing skin hydration and/or temperature or by changes in molecular structure of the compound. Hydrating the skin with occlusive dressings eg, plastic wrap, a tight fitting diaper or one covered with plastic pants, plastic tape or dermatological patches can increase corticosteroids penetration by up to 10-fold.
Absorption of topical corticosteroids has been greatly increased by altering the product vehicle or the drug substance itself. Vehicles containing substances that solubilize the corticosteroid enhance absorption. Increasing the concentration of the drug increases skin penetration but also may increase wastage of the drug. Decreasing drug particle size has been shown to increase topical bioavailability. Increased percutaneous absorption of corticosteroids also occurs when the skin mucosa is abraded or inflamed, when body temperature is elevated, with prolonged use, or with extensive use.
There is some systemic absorption of topical corticosteroids through the oral mucosa; absorption increases with increased potency and prolonged use.
Biotransformation: Primarily in skin; once absorbed systemically, in the liver. Corticosteroids that contain substituted 17-hydroxyl groups or that are fluorinated are resistant to local metabolism in the skin. Repeated application results in a cumulative depot effect in the skin, which may lead to a prolonged duration of action, increased side effects, and increased systemic absorption.
Neomycin: Although not absorbed through intact skin, topical neomycin is readily absorbed from large denuded, burned or granulated areas. Greater and more rapid absorption occurs with neomycin cream than with ointment.
