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CHAPTER 29 SUNSCREENS
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CHAPTER 30 Retinoids
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Leslie Baumann, MD Sogol Saghari, MD
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of retinol4 Twelve years later, retinol was successfully synthesized and soon became commercially available Since that time, the retinoid field has proliferated with compounds, now numbering more than 2500 products5 In fact, many generic forms of tretinoin are currently available in the United States and retinoids are even combined with medications such as antibiotics, as in Ziana, and hydroquinone, as in Tri-Luma Initially, a retinoid was defined as a compound the structure and action of which resembled the parent compound retinol Through the last several decades, chemists have made extensive modifications to the naturally-occurring molecule that have resulted in the development of three generations of retinoids (Fig 30-1) The latest retinoids bear little structural resemblance to retinol but still qualify as retinoids because they can exert their biologic action through the same nuclear receptors modulated by the active natural metabolite of vitamin A, retinoic acid Retinoic acid is a lipid-soluble molecule known to affect cell growth, differentiation, homeostasis, apoptosis, and embryonic development In fact, retinoids elicit their effects at the molecular level by regulating gene transcription and affecting activities such as cellular differentiation and proliferation (Fig 30-2 for the mechanism of action of retinoids in acne) These agents can act directly, by inducing transcription from genes with promoter regions that contain retinoid response elements or indirectly by inhibiting the transcription of certain genes6 Three domains within the retinoic acid molecule govern its biologic activity: an acidic function at one extreme and a lipophilic domain at the other, linked by a group that determines their relative spatial orientation7 Synthetic retinoids also require an acidic function pointing away from a lipophilic portion for receptor affinity and transcription The successive generations of retinoids have resulted from modification of the retinoic acid skeleton with structural rigidification, through addition of aromatic rings in place of the vulnerable double bonds found in retinoic acid This makes the third-generation retinoids more photostable when compared to the first- and secondgeneration molecules; some compounds within this family have displayed significantly reduced irritation potential8
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Retinoids are a family of compounds derived from vitamin A that includes betacarotene and other carotenoids, retinol, tretinoin, tazarotene, and adapalene For many years, retinoids have been used topically and systemically for the treatment of dermatologic diseases, particularly acne The potential benefits of retinoids for the treatment and prevention of photoaging have also been explored through the last two decades This research has led to a greater understanding of the etiology of skin aging Concurrent but unrelated research has also recently demonstrated that doses of ultraviolet (UV) light too low to cause visible skin reddening are still capable of activating the enzymatic machinery that leads to photoaging1 The first anecdotal evidence that retinoids could improve aged skin was seen in female patients being treated for acne These patients reported that their skin felt smoother and less wrinkled after treatment2 This observation was followed by a clinical trial that showed that patients treated with tretinoin demonstrated improvement of sunlight-induced epidermal atrophy, dysplasia, keratosis, and dyspigmentation3 A plethora of clinical trials have confirmed such early observations The data were submitted to the US Food and Drug Administration (FDA), which later approved tretinoin (brand name Renova ) for use against photodamage Although there are many different topical retinoids on the market today that are also useful against photodamage, Renova and Avage are the only topical agents approved specifically for this purpose Retinol, the metabolic precursor of tretinoin, is often added to overthe-counter (OTC) cosmetic formulations that are touted as antiwrinkle creams This chapter will focus on the antiaging activity of topical retinoids It should be noted, though, that oral retinoids are also being used to treat photodamage
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