Dermatological pharmacology

Introduction

The skin consist of layers called the epidermis and certain appendages such as sweat glands, sebaceous glands (which secrete an oily substance), hair, and nails. There also exists a subcutaneous layer beneath the dermis. The outermost layer of the epidermis is termed the stratum corneum. It consist principally of dead epithelial cells that are filled with a protein, keratin, which waterproofs and toughens the skin. Underlying the stratum corneum are layers comprising granular spinous cells, keratinocytes, melanocytes, and Langhans cells. The dermis, which is below the epidermis, comprises connective tissue and a number of different cell types, it maintains and nourishes the epidermis through its network of capillaries and lymphatic vessels, sweat glands and hair follicles, which originate in the dermis and penetrate the stratum corneum of the epidermis, a potential route of penetration by drugs or chemicals. The subcutaneous layer is the innermost layer and is composed of loose connective tissue and many fat cells. It provides some degree of insulation and is a location for food storage and the site for subcutaneous injection.

Few chemicals or drugs are absorbed rapidly from intact skin. In fact, the skin effectively retards the diffusion and evaporation even of water except through the sweat glands. There are, however, a few notable exceptions (e.g., certain types of nerve gases, as well as insecticides, scopolamine, and nitroglycerin), and instances where a penetration enhancer (e.g., dimethyl sulfoxide) serves as a vehicle for the drug.

Several factors affect the transport of drugs through the skin (percutaneous) once they are applied topically. The absorption of drugs through the skin is enhanced if the drug is highly soluble in the fats (lipids) of the subcutaneous layer. The addition of water (hydration) to the stratum corneum greatly enhances the percutaneous transport of corticosteroids (anti-inflammatory steroids) and certain other topically applied agents. Hydration can be effected by wrapping the appropriate part of the body with plastic film, thereby facilitating dermal absorption. If the epithelial layer has been removed (denuded) by abrasion or burns, or if it has been affected by a disease, penetration of the drug may proceed more rapidly. A drug will be distributed (partitioned) between the solvent and the lipids of the skin according to the solubility of the solvent in water or lipids. Topical absorption of drugs is facilitated when they are dissolved in solvents that are soluble in both water and lipids. Highly water-soluble polar molecules, which have a lesser tendency to solubility in lipids, essentially cannot be absorbed percutaneously. Thus, a drug penetrates the skin at a rate determined primarily by its tendency to dissolve in water, or lipids, or both.

Topically applied drugs

Topical application of drugs provides a direct, localized effect on a specific area of the skin. When drugs are applied topically to the skin, they may be dissolved in a variety of vehicles or formulations, ranging from simple solutions to greasy ointments. The particular type of dermal formulation used (powder, ointment, etc.) depends, in part, on the type of skin lesion or disease process.

Topically applied medications can relieve itching, exert a constricting or astringent action on the pores, or dissolve or remove the epidermal layers. Other pharmacologic effects from topically applied drugs include antibacterial, anti-inflammatory, antifungal, and antiparasitic actions. Analgesic balms (e.g., wintergreen oil or methyl salicylate) have been used topically to relieve minor muscle aches and pains.

Drugs may also be applied to mucous membranes, including those of the conjunctiva, mouth, nasopharynx, vagina, colon, rectum, urethra, and bladder. They may either exert a local action or be absorbed into the bloodstream to act elsewhere, Examples include nitroglycerin, which is absorbed from under the tongue (sublingually) to act on the heart and relieve anginal pain, and trifluoperazine, which is a tranquilizer sometimes taken in suppositories. Nasal insufflation, or inhalation, involves the local application of a drug to the mucous membranes of the nose to achieve a systemic action. This represents an effective delivery route of antidiuretic hormone and its analogues in the treatment of diabetes insipidus. Relatively unsuccessful efforts have been made to get hormones of larger weight, such as insulin or growth hormone, to penetrate the mucous membranes of the nasal cavity, thereby avoiding the need to inject such hormones. Although certain medications can be applied successfully to mucous membranes, the topical application of drugs to the skin represents a more widespread and therapeutic method of administration. Although certain antibiotics are used topically, their use should be restricted to the most superficial skin infections. Antibiotics are more often administered systemically. The tetracyclines have been used topically for the treatment of acne. Skin disorders caused by fungi can be treated with either antibiotics or antifungal drugs.