Current Use and Future Potential Role of Retinoids in Dermatology

Abstract

Since their introduction 15 years ago, retinoids have been increasingly used for topical and systemic treatment of psoriasis and other hyperkeratotic and parakeratotic skin disorders, keratotic genodermatoses, severe acne and acne-related dermatoses, and also for therapy and/or chemoprevention of skin cancer and other neoplasia. Oxidative metabolites of vitamin A (retinol) are natural retinoids present at low levels in the peripheral blood. Synthetic retinoids are classified into 3 generations including nonaromatic, monoaromatic and polyaromatic compounds. They are detectable in plasma 30-60 minutes after systemic administration, and reach maximum concentrations 2 to 4 hours later. Elimination half-life is 10 to 20 hours for isotretinoin, 80 to 175 days for etretinate and 2 to 4 days for, trans-acitretin; the latter, however, partially converts into etretinate. Retinoid concentrations in skin are rather low in contrast to subcutaneous fat tissue. Intracellularly, retinoids interact with cytosolic proteins and specific nuclear receptors. Two classes of nuclear receptors have been suggested to mediate retinoid activity at the molecular level, RARs and RXRs. The expression of retinoid receptors is tissue specific; skin mainly espresses RAR gamma and RXR alpha. Retinoids affect epidermal cell growth and differentiation as well as sebaceous gland activity and exhibit immunomodulatory and anti-inflammatory properties. Current retinoid research targets the development of receptor-selective retinoids for tailoring and/or improving their therapeutic profile. Currently, tretinoin is used systemically for acute promyelocytic leukaemia, etretinate and acitretin for psoriasis and related disorders, as well as other disorders of keratinisation and isotretinoin for seborrhoea, severe acne, rosacea and acneiform dermatoses. Systemic retinoids are also applied for chemoprevention of epithelial skin cancer and cutaneous T cell lymphoma. The major adverse effect of retinoids is teratogenicity; all other adverse effects are dose-dependent and controllable. Contraception is, therefore, essential during retinoid treatment in women of child-bearing age. Clinical monitoring requires physical examination for adverse effects every 3 to 4 weeks and proper laboratory investigations, also including analysis of retinoid bioavailability in selected cases. Topical retinoids are rapidly developing at present and seem promising for the future; their clinical application includes acne, aging, photodamage, precanceroses, skin cancer and disorders of skin pigmentation. The development of receptor-specific retinoids for topical treatment of psoriasis and/or acne may lead to interesting new compounds based on our current concepts of retinoid function.

The neurobiology of retinoic acid in affective disorders

“…These primarily come from studies of isotretinoin (Accutane), or 13-cis-RA, a drug that inhibits sebaceous gland function, keratinization, and inflammatory responses, and is approved by the Food and Drug Administration (FDA) for the treatment of cystic and nodular acne Goulden et al 1995;Orfanos et al 1997). Isotretinoin is identical to the predominant physiological form of RA, all-trans RA, differing only in molecular geometry, having its double bond at C13 in cis conformation ( Fig.…”

Drug Approval Summaries: Arsenic Trioxide, Tamoxifen Citrate, Anastrazole, Paclitaxel, Bexarotene

“…Retinoids play critical roles in normal development and physiology by modulating cell growth, division, reproduction, differentiation, and immune function. They are also capable of inhibiting cell growth, inducing differentiation, and inducing apoptosis (programmed cell death) in a variety of tumor cell lines [22][23][24].…”

Uso da isotretinoína no tratamento da acne e sua relação com a halitose

“…As alterações nas mucosas e pele são decorrentes da diminuição da produção de sebo, redução da espessura do estrato córneo (FONSECA, 2009) e alteração da função de barreira da pele (ORFANOS et al, 1997). A secura labial ocorre em 100% dos casos, queilite em 95% (SAMPAIO; RIVITTI, 2008), já podendo ser observadas, nos primeiros dez dias do tratamento (CHIVOT, 2005).…”

“…Os retinóides atuam no crescimento e diferenciação das células epidérmicas, assim como interferem na atividade da glândula sebácea e possuem propriedades imunomoduladoras e anti-inflamatórias (ORFANOS et al, 1997). Os retinóides tópicos são, amplamente, utilizados no tratamento do fotoenvelhecimento cutâneo, sendo sua eficácia bem estabelecida (FONSECA, 2009).…”