Acitretin Retinol

Vitamin A (retinols) plays a role in epithelial function and the retinoic acid derivative, acitretin (Neotigason, orally), inhibits psoriatic hyperkeratosis over 4-6 weeks. Acitretin should be used in courses (6-9 months) with intervals (3-4 months). It is teratogenic, like the other vitamin A derivatives. Rigorous precautions for use in women of childbearing potential are laid down by the manufacturer and must be followed, including contraception for 2 years after cessation, because the drug is stored in the liver and in fat and released over many months. The plasma t) is 3 months. It can cause other serious toxicity (see Vitamin A, p. 739). Tazarotene, a topical retinoid, is of some benefit in mild psoriasis, but is irritant. 

Hepatomegaly is an adverse effect of retinol and tretinoin. Transient slight rises in liver enzymes, notably aspartate transaminase, alanine transaminase, and alkaline phosphatase, are common, but some cases of hepato-toxicity due to etretinate and acitretin (SEDA-20, 154) have also been reported (76), as has cholestatic jaundice due to etretinate (77). Etretinate may have played a role in a case of liver failure leading to death (76). 

Retinoids include natural compounds and synthetic derivatives of retinol that exhibit vitamin A activity. First-generation retinoids include retinol, tretinoin (aU-ironi-retinoic acid), isotretinoin (13-cu-retinoic acid), and alitretinoin (9-cw-retinoic acid). Second-generation retinoids, also known as aromatic retinoids, were created by alteration of the cyclic end group and include acitretin. Third-generation retinoids contain further modifications and are called arotinoids. Members of this generation include tazarotene and bexarotene. Adapalene, a derivative of naphthoic acid with retinoid-like properties, does not fit precisely into any of the three generations. 

A condition similar to vitamin A (retinol) overdosage may occur if acitretin or isotretinoin are given with vitamin A. 

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 parent compound in the vitamin A group is called sdl-trans retinol (Fig. lA) [4]. Its aldehyde and acid forms are retinal (Fig. IB) and retinoic acid (Fig. 1C). The active form of vitamin A in vision is ll-cis retinal (Fig. ID), and a therapeutically useful form (accutane, isotretinoin) is l3-cis retinoic acid (Fig. IE). Retinyl palmitate (Fig. IF) is a major storage form, and retinoyl p-glucuronide is a biologically active, relatively non-toxic water-soluble metabolite (Fig. IG). A synthetic aromatic analog (etretin, acitretin), shows therapeutic usefulness (Fig. IH). Finally, p-carotene, a major provitamin A carotenoid, is shown in Figure II. 

Figure 1. Formulas of major retinoids and of P-carotene. A, all-tranj retinol B, all-tranj retinal C, all-rran retinoic acid D, 11-cw retinal E, 13-cw retinoic acid F, all-tran retinyl palmtate G, ai -trans retinoyl p-glu-curonide H, the trimethyl methoxyphenol analog of all-rra 5 retinoic acid (etretin, acitretin) I, all-rra 5 p-carotene. From [5], p. 110, reprinted with the permission of the International Life Sciences Institute, Washington DC 20036-4810, Copyright 1996.

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