Dermatology synthetic retinoids

Retinoids are a family of naturally occurring and synthetic analogues of vitamin A. The skin of subjects deficient in vitamin A becomes hyperplastic and keratotic (phrynoderma, or toad skin). While natural vitamin A is occasionally employed therapeutically, synthetic retinoids are more effective and represent a major advance in dermatological pharmacotherapy. Retinoids have myriad effects on cellular differentiation and proliferation it is likely that nuclear retinoic acid receptors mediate these effects by activating gene expression in a manner analogous to receptors for steroid hormones and thyroid hormones. Despite a common mechanism of action, however, retinoids vary widely in their physiological effects. 

The development of biologically active, less-toxic synthetic derivatives of retinoic acid has lead to a major advance in dermatologic therapeutics. Isotretinoin (13-ci y-retinoic acid, Accutane) is the first of these synthetic retinoids to be marketed for the treatment of severe, recalcitrant cystic acne in the United States. 

During the past year (1982-1983), two synthetic retinoids have been introduced into the clinical practice of dermatology. In the United States, isotretinoin (E6) (13-cw-retinoic acid, Accutane) was approved for the treatment of severe... 

Retinoids have multiple properties in embriogenesis, growth control and differentiation of adult tissues, reproduction, and sight. In dermatology their use is well established for psoriasis, hereditary disorders of keratinization, acne, and skin aging. The most commonly used retinoids are aH-trans retinoic acid (tretinoin used topically), 13-cis retinoic acid [isotretinoin used both orally and topically), retinaldehyde/retinal and retinol [both of which are used topically). In addition there are the synthetic retinoids etretinate, acitretin, adapalene, tazarotene, etc. 

The results of this study, in which a synthetic retinoid was found to have a profound beneficial effect in the treatment of disorders of keratinization, should be of importance to areas other than dermatology. For instance, preneoplastic squamous metaplasia of tracheo-bronchial and urinary bladder epithelia may be other keratinizing disorders of man that could be successfully treated with the synthetic retinoids, as suggested by Sporn . Finally, patients with these cutaneous diseases, which have responded to 13-cis retinoic acid, may provide useful information in the evaluation of newer and potentially more potent and less toxic synthetic retinoids. 

Etretinate, a synthetic aromatic retinoid, has been used as an investigational drug in many thousands of patients throughout the world for various dermatologic disorders it is commercially available by prescription in several European countries for treatment of psoriasis and some disorders of keratinization. As with isotretinoin, the side effects manifested during therapy with etretinate are predominantly mucocutaneous. 

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