Mucocutaneous Side Effects
Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish in Retinoids in Dermatology, 2019
Retinoids are derivates of natural and synthetic analogs of vitamin A that have a wide variety of pharmaco-physiologic effects (1). Following their first approval in the treatment of hyperkeratotic skin diseases in the 1940s, they have become major therapeutic agents for a wide spectrum of skin diseases, with good therapeutic results and minimal toxicity ratios (1–11). With the use of such a wide spectrum, many side effects can be seen in different systems during retinoid therapies. Most of these side effects are acute, dose-dependent in incidence, with variable severity, usually well-tolerated, reversible on discontinuation of treatment, and most commonly affecting the skin and mucous membranes. The side effect profile and severity of these agents may change according to the nature of the molecule. While mucosal dryness is more common with isotretinoin use, acitretin is associated with higher incidences of alopecia and palmoplantar peeling, in addition to mucocutaneous and ocular side effects that are milder with bexarotene as compared to other retinoids (3–9).
Small-Molecule Targeted Therapies
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
The retinoids are natural and synthetic derivatives of vitamin A that regulate a variety of important cellular functions. Retinol (Figure 6.106), also known as vitamin A1, is a vitamin found in many food types and used as a dietary supplement to treat and prevent vitamin A deficiency. In the body retinol is converted to retinal and then retinoic acid which acts on cell-surface receptors to control processes including cell growth and metabolism (Figure 6.105). In particular, it is a regulator of epithelial and bone tissue cell growth and differentiation, and so analogues have been developed for use in skin-related proliferative diseases such as psoriasis and bone tissue disorders. Through the activation of tumor-suppressor genes, it is also known to play a role in maintaining vision and immune function. Retinol was discovered in 1909, isolated in 1931 and first synthesized in 1947, and dietary sources rich in the molecule include dairy products, meat, and fish. All-trans-retinoic acid (RA) works by activating the Nuclear Retinoic Acid receptors (RARs), while 9-cis-retinoic acid activates the non-classical nuclear Retinoid X Receptors (RXRs) along with the RARs. Altogether, there are six genes encoding the retinoid receptors: RARa, RARb, and RARg, and RXRa, RXRb, and RXRg (Figure 6.105).
New Models to Assess in Vitro Action of Retinoids
Francis N. Marzulli, Howard I. Maibach in Dermatotoxicology Methods: The Laboratory Worker’s Vade Mecum, 2019
Retinoids are key modulators of the cellular functions in many tissues including the skin (Shapiro, 1986). All-fraAis-retinoic acid (ATRA), a metabolite of vitamin A, and synthetic retinoids have long been used for the treatment of skin diseases (Schaefer and Reichert, 1990), including acne and psoriasis. At least two major cell types of the skin, keratinocytes and fibroblasts, are targets for the action of retinoic acid. Retinoids inhibit the differentiation process of cultured keratinocytes (Fuchs and Green, 1981) and induce in vivo an alternative pathway to normal differentiation, leading to epidermal hyperproliferation (Fisher et al., 1991). In fibroblasts, retinoids can modulate the synthesis of several proteins, such as collagens and collagenases, essential for the integrity of the extra-cellular matrix (Fisher et al., 1996).
PLGA-PEG-RA-based polymeric micelles for tumor targeted delivery of irinotecan
Published in Pharmaceutical Development and Technology, 2018
Jaber Emami, Parnian Maghzi, Farshid Hasanzadeh, Hojjat Sadeghi, Mina Mirian, Mahboubeh Rostami
Retinoids are a class of compounds that are structurally related to vitamin A. They exhibit antiproliferative and differentiative effects, and thus are used for cancer prevention and treatment. RA has been used in combination with chemotherapeutic agents for the treatment of various cancers such as Kaposi’s sarcoma, head and neck squamous cell carcinoma, ovarian carcinoma, and neuroblastoma (Siddikuzzaman and Berlin Grace 2011). Retinoids have been reported to reduce second malignancies in the liver and in the breast (Hong and Sporn 1997; Nason-Burchenal and Dmitrovsky 1999), to treat acute promyelocytic leukemia (APl) (Adamson 1996) when combined with other drugs, and to increase the antiproliferative and prodifferentiative effects on colon cancer cells (Miller 1998; Brtko and Thalhamer 2003). The most effective clinical usage of all-trans RA in human disease was observed in the treatment of a rare leukemia, APL (de The et al. 1990). In humans, retinoids reversed premalignant human epithelial lesions, induced the differentiation of myeloid cells, and also helped in the prevention of lung, liver, and breast cancer (Bukhari et al. 2007).
Alitretinoin for the treatment of severe chronic eczema of the hands
Published in Expert Opinion on Pharmacotherapy, 2022
Maddalena Napolitano, Luca Potestio, Mario De Lucia, Mariateresa Nocerino, Gabriella Fabbrocini, Cataldo Patruno
The first-line therapeutic strategies for the management of CHE include skin education program and lifestyle changes [6], such as the avoidance of patch test proven contact allergens or irritants. The frequent application of emollients strongly helps the restoration of skin and is considered as the cornerstone treatment [6]. Topical corticosteroids or calcineurin inhibitors are prescribed as anti-inflammatory drugs. However, up to 65% of patients require systemic options [13]. Alitretinoin is the first systemic therapy in patients with severe CHE refractory also to potent topical corticosteroids approved in the European Union (EU) [14]. It is an endogenous retinoid, structurally related to vitamin A [15]. Retinoids are a family of natural and synthetic compounds which are used for different skin disorders [15].
Antenatal Diagnosis of Fetal Retinoid Syndrome at 20 Weeks of Gestation: A Case Report
Published in Fetal and Pediatric Pathology, 2018
Hakan Erenel, Aysegul Ozel, Funda Oztunc, Osman Kizilkilic, Nil Comunoglu, Seyfettin Uludag, Riza Madazli
Retinoids are a specific family of vitamin A derivatives including several subtypes such as first, second and third generation. Retinol, retinal, tretinoin (retinoic acid), isotretinoin, and alitretinoin are first generation retinoids. Etretinate and its metabolite acitretin are second-generation retinoids (4). Adapalene, bexarotene, and tazarotene are third generation retinoids (5). Retinoids are used in several conditions such as acne, psoriasis and cancer. One of these retinoids is isotretinoin (13-cis-retinoic acid), which was licensed in the United States in 1982 under the brand name Accutane (2). In 1985, Lammer et al. summarized outcomes of 154 pregnant patients with the exposure to isotretinoin (2). After excluding elective and spontaneous abortions, analysis of 21 malformed infants showed that most common craniofacial malformation was microtia or anotia. Maldevelopment of facial bones and calvarium, micrognathia, cleft palate, flat and depressed nasal bridge, hypertelorism, cerebellar hypoplasia, agenesis of the vermis were described cranial anomalies. They also reported several forms of conotruncal malformations such as transposition of great vessels, tetralogy of Fallot, double-outlet right ventricle, truncus arteriosus communis and supracristal ventricular septal defect in conjunction with abnormalities of thymic morphogenesis (ectopia, hypoplasia, aplasia) (2). In our case, fetal anomalies were observed in most of the above-mentioned regions.
Related Knowledge Centers
- Chemical Compound
- Vitamer
- Vitamin A
- Epithelium
- Tumor Suppressor Gene
- Skin Cancer
- Alitretinoin
- Kaposi's Sarcoma
- Tretinoin
- Acute Promyelocytic Leukemia