Tretinoin, also known as all-trans retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream, gel or ointment. For leukemia, it is taken by mouth for up to three months. Topical tretinoin is also the most extensively investigated retinoid therapy for photoaging.Common side effects when used as a cream are limited to the skin and include skin redness, peeling, and sun sensitivity. When used by mouth, side effects include shortness of breath, headache, numbness, depression, skin dryness, itchiness, hair loss, vomiting, muscle pains, and vision changes. Other severe side effects include high white blood cell counts and blood clots. Use during pregnancy is contraindicated due to the risk of birth defects. It is in the retinoid family of medications.Tretinoin was patented in 1957, and approved for medical use in 1962. It is on the World Health Organizations List of Essential Medicines. Tretinoin is available as a generic medication. In 2019, it was the 244th most commonly prescribed medication in the United States, with more than 1 million prescriptions. Medical uses
Skin use
Tretinoin is most commonly used to treat acne, both inflammatory and noninflammatory. Multiple studies support the efficacy of topical retinoids in the treatment of acne vulgaris. It is sometimes used in conjunction with other topical acne medications to enhance their penetration. In addition to treating active acne, retinoids accelerate the resolution of acne-induced postinflammatory hyperpigmentation.
Mechanism of action
For its use in cancer, its mechanism of action is unknown, but on a cellular level, laboratory tests show that tretinoin forces APL cells to differentiate and stops them from proliferating; in people there is evidence that it forces the primary cancerous promyelocytes to differentiate into their final form, allowing normal cells to take over the bone marrow. Recent study shows that ATRA inhibits and degrades active PIN1.For its use in acne, tretinoin (along with other retinoids) are vitamin A derivatives that act by binding to two nuclear receptor families within keratinocytes: the retinoic acid receptors (RAR) and the retinoid X receptors (RXR). These events contribute to the normalization of follicular keratinization and decreased cohesiveness of keratinocytes, resulting in reduced follicular occlusion and microcomedone formation. The retinoid-receptor complex competes for coactivator proteins of AP-1, a key transcription factor involved in inflammation. Retinoids also down-regulate expression of toll-like receptor (TLR)-2, which has been implicated in the inflammatory response in acne. Moreover, tretinoin and retinoids may enhance the penetration of other topical acne medications.The combination of the 10% benzoyl peroxide and light results in more than 50% degradation of tretinoin in about 2 hours and 95% in 24 hours. This lack of stability in the presence of light and oxidizing agents has led to the development of novel formulations of the drug. When microencapsulated tretinoin is exposed to benzoyl peroxide and light only 1% degradation takes place in about 4 hours and only 13% after 24 hours. Biosynthesis
Tretinoin is synthesized from beta-carotene.