TY - JOUR T1 - INHIBITION OF KERATINIZING STRUCTURES BY SYSTEMIC DRUGS JF - Pharmacological Reviews JO - Pharmacol Rev SP - 653 LP - 672 VL - 15 IS - 4 AU - PETER FLESCH Y1 - 1963/12/01 UR - http://pharmrev.aspetjournals.org/content/15/4/653.abstract N2 - A variety of systemically administered chemical agents interferes with the development of human hair, horny layer, or both. These agents include vitamin A, thallium, antineoplastic compounds, hypocholesteremic drugs, chloroprene dimers, mimosine, and anticoagulants. As a general rule, the hair root is more easily affected by these compounds than the epidermis. Only the growing hairs are attacked; hence the scalp is the most commonly involved area. Disturbed epidermal differentiation follows mainly the administration of hypocholesteremic drugs. The mechanisms of action of these compounds are incompletely understood. Vitamin A may divert cytoplasmic metabolic processes from keratin formation to mucopolysaccharide synthesis or may act by releasing a protease. Thallium interferes with the utilization or incorporation of cystine. The antineoplastic drugs inhibit mitoses in the rapidly proliferating hair matrix in a variety of ways. Hypocholesteremic drugs possibly prevent the synthesis of a proteohipid cement, while the modes of action of the chioroprene dimers, mimosine, and anticoagulants are essentially unknown. It is obvious, therefore, that hair loss and disturbed epidermal differentiation are nonspecific effects, resulting from a variety of mechanisms. Few attempts have been made to correlate cutaneous effects or disease conditions with other pharmacologic actions of these compounds. The specific influence of vitamin A and especially of its derivatives should be studied in greater depth. Inhibition of hair growth has been used as a measure of the toxicity of cancer chemotherapeutic drugs. On the whole, however, the potentialities of these agents for pharmacologic and dermatologic research have not been sufficiently exploited. Abnormal developments of horny structures are easily observable, accessible, and essentially harmless side-effects of drugs. Broadening of their study would enlarge our understanding not only of the biology of these processes, but also of the effects of a number of drugs. Such investigations could make important contributions to the therapy of many essentially incurable scaling skin diseases which affect a large proportion of the population, and could help in the fight against neoplastic diseases. ER -