Mechanism of Action of Topical Retinoids
Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish in Retinoids in Dermatology, 2019
Adapalene is a chemically stable, photostable, and highly lipophilic synthetic retinoid which has a selective affinity for retinoid receptors RAR-β and RAR-γ. Although it does not bind to CRABPs, it has been shown to induce expression of CRABP-II. Its FDA-approved indication is acne. Due to its lipophilic properties, it is selectively uptaken by the follicular unit, and that may contribute to its success in anti-acne activity. It normalizes the differentiation and keratinization of follicular epithelial cells, thus leading to a comedolytic effect. In addition, in contrast to other classical retinoids, adapalene is a naphthoic acid derivate which has an NSAID-like structure and increased anti-inflammatory effect. It decreases leukotriene and prostaglandin production through inhibition of lipoxygenase activity and arachidonic acid metabolism (25). Adapalene can modulate the epidermal immune system by increasing CD1d expression and decreasing IL-10 expression by keratinocytes. Decreasing expression of toll-like receptor-2 (TLR-2) by keratinocytes can help to explain the anti-inflammatory activity of adapalene observed in clinical practice (26). These mechanisms may explain the reason for decreased risk of irritation with adapalene. Systemic absorption of adapalene is negligible. Only trace amounts have been found in the plasma of acne patients following chronic topical application of adapalene.
Basic dermatology in children and adolescents
Joseph S. Sanfilippo, Eduardo Lara-Torre, Veronica Gomez-Lobo in Sanfilippo's Textbook of Pediatric and Adolescent GynecologySecond Edition, 2019
When instituting new acne therapy, it is of utmost importance to counsel patients that 2–3 months of consistent use is necessary to determine the efficacy of any therapeutic regimen. Topical treatments are usually effective in patients with primarily comedonal acne. All patients with acne should be started on a topical retinoid such as adapalene, tretinoin, or tazarotene. Topical retinoids normalize the abnormal follicular keratinization that contributes to acne and have anti-inflammatory properties. Patients should be warned of potential irritation as well as the possibility of a pustular flare during the first month of use. Adapalene 0.1% has become available over the counter in the United States, but the other topical retinoids require a prescription. It is important to note that tazarotene is a topical medication that is contraindicated with pregnancy, and it requires simultaneous contraception. Azelaic acid, a comedolytic dicarboxylic acid that has modest activity against P. acnes, can be prescribed during pregnancy, as it has minimal systemic absorption, and is, therefore, the safest comedolytic to use during pregnancy. Azelaic acid is also helpful as an adjunct to acne therapy in darker-skinned individuals who exhibit postinflammatory hyperpigmentation, as hypopigmentation can be a side effect of this medication.33
Acne Scarring and Patients of African Descent
Antonella Tosti, Maria Pia De Padova, Gabriella Fabbrocini, Kenneth R. Beer in Acne Scars, 2018
The retinoids, such as tretinoin, adapalene, and tazarotene, represent a class of topicals that not only treat acne but also hyperpigmentation and, therefore, should be initiated early in treatment and remain as maintenance therapy. It is beneficial to explain to the patient the dual role of retinoids in treatment of acne and hyperpigmentation to foster improved adherence. Retinoids are not only well known for their effect on non-inflammatory and inflammatory acne but they can also directly affect PIH in dark-skinned individuals [25–27].
Adverse events related to topical drug treatments for acne vulgaris
Published in Expert Opinion on Drug Safety, 2020
Agnieszka Otlewska, Wojciech Baran, Aleksandra Batycka-Baran
Adapalene is synthetic, third-generation topical retinoid derived from naphthoic acid [30]. The available topical formulations of adapalene are 0.1% gel, cream, solution, and 0.3% gel [28]. Adapalene can be used in monotherapy or in combination therapies [30]. An important aspect in the treatment of acne with adapalene is that it can be safely used for acne in children who have not reached adolescence [26]. However, the safety and efficacy of this medicine in children under the age of 12 years have not been determined [12]. Topical adapalene is usually administered once-nightly to acne-prone skin. When applying it is recommended to put a thin film of the product on the skin and avoid eyes and mucous membranes contact with the drug [12]. Most common adverse effects are related to local side effects, including erythema, scaling, dryness, pruritus, and burning, but usually the intensity of the symptoms is mild [30]. The intensity of skin irritation related to topical treatment with adapalene increases in intensity to a maximum at week 2 of treatment and regularly decreases to week 12 [31].
Emerging drugs for the treatment of acne: a review of phase 2 & 3 trials
Published in Expert Opinion on Emerging Drugs, 2022
Siddharth Bhatt, Rohit Kothari, Durga Madhab Tripathy, Sunmeet Sandhu, Mahsa Babaei, Mohamad Goldust
Topical usage of retinoids achieves an effective concentration in the skin and precludes from getting systemic adverse effects. Topical retinoids while targeting the epidermal proliferation, reduces the earliest precursor lesions of acne viz comedone. Thereby, making it the first-line therapy in the management of acne vulgaris currently. Retinoids, especially tretinoin being photolabile should ideally be applied during the night. Adapalene and tazarotene in this respect have the added advantage of being photostable and can be applied during the day. It has additional anti-inflammatory properties due to the inhibition of the lipo-oxygenase pathway and chemotaxis, along with free oxygen radical release from neutrophils. Adapalene at 0.3% has also been shown to reduce scar formation and pigmentation due to acne lesions. Erythema, scaling, pruritus, burning, stinging, dryness and irritation are common side effects. It can rarely lead to allergic contact dermatitis.
Nanotechnology-based formulations toward the improved topical delivery of anti-acne active ingredients
Published in Expert Opinion on Drug Delivery, 2021
Ana Cláudia Paiva-Santos, Filipa Mascarenhas-Melo, Sara Cabanas Coimbra, Kiran D. Pawar, Diana Peixoto, Raquel Chá-Chá, André RTS Araujo, Célia Cabral, Selmo Pinto, Francisco Veiga
Topical treatment is used as the first choice in mild to moderate situations of acne, including retinoids, benzoyl peroxide (BENP), azelaic acid (AZA), topical antibiotics, and combined therapy. Topical retinoids, as adapalene (ADA), tretinoin (TRE), and isotretinoin (ITR), are used as first-line therapy for primary acne lesions [15–17]. Nevertheless, those molecules evidence side effects, as erythema, eczematous irritation, skin peeling, dryness, and photosensitivity [18–20]. For inflammatory lesions, BENP is recommended since it has a bactericidal effect. However, BENP can cause irritant dermatitis with dryness, erythema, and peeling as side effects [12,15]. AZA has an anti-inflammatory effect and reduces the formation of comedones. Still, it can cause some photosensitivity, skin irritation, and redness [10,12]. Clindamycin (CLY), erythromycin (ERY), and tetracycline (TEY) are effective topical antibiotics used to treat mild to moderate acne, but can cause skin irritation [15].
Related Knowledge Centers
- Acne
- Benzoyl Peroxide
- Retinoid
- Tazarotene
- Tretinoin
- Hyperpigmentation
- Clindamycin
- Off-Label Use
- Keratosis Pilaris
- Antimicrobial