Retinoids in Dermatology

2 Retinoids in Dermatology 13-Qs-retinoic acid (isotretinoin, Accutane ) is used orally, and all-trans-retinoic acid (Tretinoin ) topically, for treatment of severely disfiguring cystic acne. Etretinate (the trimethoxyphenyl analog of retinoic acid) and tazarotene (a receptor-specific retinoid) are used topically for the treatment of psoriasis. They are effective in cases in which other therapy has failed, and at lower levels than are required for the control of tumor development in experimental animals, although they have heen associated with hirth defects (Section 2.5.1.1 fohnson and Chandrarama, 1999). 

In addition to their importance as precursors of vitamin A, carotenes can also act, at least in vitro (and under conditions of low oxygen tension), as antioxidants, trapping singlet oxygen generated by photochemical reactions or lipid peroxidation of membranes (Burton and Ingold, 1984). Studies with 

The studies were performed on established heavy smokers and people who had been exposed to asbestos dust some years previously. It has been suggested that whereas /3-carotene may inhibit induction of cancers by reactive oxygen species, it may also enhance later stages in tumor development. 

What the epidemiological studies have actually shown is a negative association between various types of cancer and the consumption of fruits and vegetables that are rich in carotenoids and a great many other potentially protective compounds (Section 14.7). It may be that /3-carotene is simply a marker for some other protective factor. 

Albert AD and YeaglePL (2000) Structural aspects of the G-protein receptor, rhodopsin. 

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Retinoids. Table 1 Indications and mode of administration of commercially available retinoids in dermatological therapy... 

Orfanos, C.E., Zouboulis, C.C., Almond-Roesler, B. and Geilen, C.C. (1997) Current use and future potential role of retinoids in dermatology. Drugs, 53, 358-388. 

Pochi, P. E., 1982, Oral retinoids in dermatology. Arch. Dermatol., 118 57-61. 

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. 

Retinoid acid is a transcription factor. Retinoids play significant roles in dermatology, in the prevention of some cancers, and in the chemistry of vision. Consequently, many works have been dedicated to fluorinated analogues of retinoids. 

Zouboulis, C.C., Retinoids — which dermatological indications will benefit in the near future Skin Pharmacol. Appl. Skin Physiol., 14, 303, 2001. 

Nguyen EH, Wolverton SE. Systemic retinoids. In Wolverton SE, ed. Comprehensive Dermatologic Drug Therapy. Philadelphia, Saunders, 2001 269-310. 

Retinoic acid, available as an oral commercial preparation for the treatment of severe cystic acne (Accutane) has been one of the great successes in dermatology. However, it is not without side effects, some of which are severe. Oral retinoids are potent teratogens, and approximately one-fourth of all exposed fetuses develop birth defects. Their teratogenic potential has led to strict guidelines governing their use in women of child-bearing potential. Other side effects, such as elevated liver function tests, elevated serum lipids, and nyctalopia have also limited their use (43). 

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