|Systematic (IUPAC) name|
|Trade names||Avita, Renova, Retin-a|
|Licence data||US Daily Med:|
|Protein binding||> 95%|
|ATC code||D10 L01|
|Molecular mass||300.4412 g/mol|
|Melting point||180 °C (356 °F)|
|(what is this?)|
Tretinoin (etymology and pronunciation) is retinoic acid in pharmaceutical form. It is the carboxylic acid form of vitamin A and is also known as all-trans retinoic acid or ATRA. It is a first generation topical retinoid commonly used to treat acne vulgaris and keratosis pilaris. It is available as a cream or gel (brand names Aberela, Airol, A-Ret, Atralin, Avita, Retacnyl, Refissa, Renova, Retin-A, Retino-A, ReTrieve, or Stieva-A). The most common strengths are 0.025%, 0.05% and 0.1%. It is also used to treat acute promyelocytic leukemia (APL), and is sold for this indication by Roche under the brand name Vesanoid. It is also available as a generic. Its isomer, isotretinoin, is also an acne drug.
Tretinoin was co-developed by James Fulton and Albert Kligman in 1969. Together, Fulton and Kligman are credited as the inventors of Retin-A. Fulton was a researcher at the University of Pennsylvania at the time. The University of Pennsylvania held the patent for Retin-A, which it licensed to pharmaceutical companies.
Tretinoin is most commonly used as a form of acne treatment. It was the first retinoid developed for this type of topical use. Tretinoin is the best studied retinoid in the treatment of photoaging. It is used by some as a hair loss treatment  and is a component of many commercial products that are advertised as being able to slow skin aging or remove wrinkles. Topical tretinoin is also used to treat and reduce the appearance of stretch marks by increasing collagen production in the dermis.
Tretinoin, marketed as Vesanoid, is used to treat at least one form of cancer (acute promyelocytic leukemia, also called acute myeloid leukemia subtype M3), usually together with other drugs, by causing the immature promyelocytes to differentiate (i.e. mature).
The pathology of the leukemia is due to the highly proliferative immature cells; retinoic acid drives these cells to develop into functional cells, which helps to alleviate the disease. It is usually prescribed for 15 days every three months at about 8–10 10-mg capsules per day.
Successfully treating acute promyelocytic leukemia (APL) with Tretinoin was a major breakthrough in APL therapy. It works in APL because the majority of cases involve a chromosomal translocation of chromosomes 15 and 17, which causes genetic fusion of the retinoic acid receptor (RAR) gene to the promyelocytic leukemia (PML) gene. This fusion PML-RAR protein is responsible for preventing immature myeloid cells from differentiating into more mature cells. This block in differentiation is thought to cause leukemia. ATRA acts on PML-RAR to lift this block, causing the immature promyelocytes to differentiate to normal mature blood cells thus decreasing promyelocytes.
In dermatological use
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When used, dryness or increased sensitivity to sunlight of the affected skin may occur. More sensitive patients may also experience redness, scaling, itching, and burning. A gradual increase in the frequency and amount of tretinoin application is best, as this allows one's skin to adequately adjust to the drug. Patients should be careful to follow their physician's recommendations when beginning a round of treatment.
As this product may cause irritation, it may indirectly increase sun sensitivity and fragility of the skin. Patients who are using the drug should apply moisturizer and sunscreen to reduce the chance of developing sunburn while using tretinoin. Additionally, patients using tretinoin should be cautious when simultaneously using other topical medications that contain salicylic acid, resorcinol, or sulfur because these medications may potentiate the drying and possibly irritating effects of tretinoin. Topical tretinoin should be avoided during pregnancy because its use has been linked to birth defects in several case reports.
In leukemia use
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There is a unique complication of retinoic acid syndrome in patients with acute promyelocytic leukemia. This is associated with the development of dyspnea, fever, weight gain, peripheral edema and is treated with dexamethasone. The etiology of retinoic acid syndrome has been attributed to capillary leak syndrome from cytokine release from the differentiating promyelocytes.
It is a teratogen, and therefore can cause birth defects and tests have shown increases in fetal skull abnormalities in rats. Women who are or may be pregnant, or who are seeking to become pregnant, are therefore warned against using it. This teratogenic effect is caused by the interference of the exogenous retinoic acid with endogenous retinoic acid signaling, which plays a role in patterning the developing embryo. However the risks of topical tretinoin to the fetus seems to be limited.
A study published by the European Respiratory Journal in 2002, suggested tretinoin can reverse the effects of emphysema in mice by returning elasticity (and regenerating lung tissue through gene mediation) to the alveoli. Studies suggested this might form a promising treatment in human emphysema patients. However, a newer follow-up study done in 2006 found inconclusive results ("no definitive clinical benefits") using vitamin A (retinoic acid) in treatment of emphysema in humans and stated further research is needed to reach conclusions on this treatment.
Tetrinoin can be synthesized from ionone.
Condensation with the carbanion from acetonitrile followed by dehydration of the initially formed carbinol gives the intermediate (). Reduction of the cyano group by diisobutylaluminum hydride leads to the corresponding imine; this hydrolyzes to aldehyde () during the acid workup. Base-catalyzed aldol condensation of that aldehyde with β-methylglutaconic anhydride () involves condensation with the activated methylene group of the anhydride and leads to the product () in which the remainder of the side chain has been added. The anhydride is then hydrolyzed to the vinylogous β-dicarboxylic acid (). The superfluous carboxyl group is removed by heating the compound in quinoline in the presence of copper to afford acid (). The terminal double bond is then isomerized by any of several methods to give tretinoin.
Etymology and pronunciation
The name tretinoin comes from trans- + retinoic, and the name isotretinoin is the same root plus the prefix iso-. The following variants apply equally to both words. Given that retinoic is pronounced //, it is natural that // is a commonly heard pronunciation. Dictionary transcriptions also include // and //.
- Baldness treatments
- Hypervitaminosis A syndrome
- Talarozole, an experimental drug potentiating the effects of tretinoin
- "Dr. James Fulton, co-creator of Retin-A and acne researcher, dies". Miami Herald. 2013-07-2013. Retrieved 2013-07-27.
|last1=in Authors list (help); Check date values in:
- MedlinePlus Drug Information: Tretinoin Topical
- Stefanaki C, Stratigos A, Katsambas A (June 2005). "Topical retinoids in the treatment of photoaging". J Cosmet Dermatol 4 (2): 130–4. doi:10.1111/j.1473-2165.2005.40215.x. PMID 17166212.
- Rogers, N and Avram, M (October 2008). "Medical treatments for male and female pattern hair loss.". Journal of the American Academy of Dermatology 59 (4): 547–566. doi:10.1016/j.jaad.2008.07.001. PMID 18793935.
- Babamiri K, Nassab R. (Jan 2010). "Cosmeceuticals: the evidence behind the retinoids.". Aesthetic Surgery Journal 30 (1): 74–77. doi:10.1177/1090820X09360704. PMID 20442078.
- Serri R, Iorizzo M. (Nov 2008). "Cosmeceuticals: focus on topical retinoids in photoaging.". Clinics In Dermatology 26 (6): 633–635. doi:10.1016/j.clindermatol.2007.09.016. PMID 18940544.
- Arthur W. Perry (2007). Straight talk about cosmetic surgery. Yale University Press. p. 63. ISBN 978-0-300-12104-9.
- Huang M, Ye Y, Chen S, Chai J, Lu J, Zhoa L, Gu L, Wang Z (1988). "Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia". Blood 72 (2): 567–72. PMID 3165295.
- Castaigne S, Chomienne C, Daniel M, Ballerini P, Berger R, Fenaux P, Degos L (1990). "All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results". Blood 76 (9): 1704–9. PMID 2224119.
- Sanz M (2006). "Treatment of acute promyelocytic leukemia". Hematology Am Soc Hematol Educ Program 2006 (1): 147–55. doi:10.1182/asheducation-2006.1.147. PMID 17124054.
- Kakizuka A (August 1991). "Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RARα with a novel putative transcription factor, PML". Cell 6 (4): 663–74. doi:10.1016/0092-8674(91)90112-C.
- Retin-A (Tretinoin)
- Tretinoin Side Effects | Drugs.com
- al.], edited by Brian K. Alldredge ... [et (2013). Applied therapeutics : the clinical use of drugs. (10th ed. ed.). Baltimore: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 948. ISBN 978-1609137137.
- Tretinoin [package insert]. Manati, Puerto Rico: Ortho Pharmaceutical; 2012.
- Meredith, Fiona M.; Ormerod, Anthony D. (31 August 2013). "The Management of Acne Vulgaris in Pregnancy". American Journal of Clinical Dermatology 14 (5): 351–358. doi:10.1007/s40257-013-0041-9.
- Lee LM, Leung CY, Tang WW, Choi HL, Leung YC, McCaffery PJ, Wang CC, Woolf AS, Shum AS. (August 2012). "A paradoxical teratogenic mechanism for retinoic acid.". Proc. Natl. Acad. Sci. U.S.A. 109 (34): 13668–73. doi:10.1073/pnas.1200872109. PMID 22869719.
- Tretinoin facts and comparisons at Drugs.com
- Loureiro KD, Kao KK, Jones KL, Alvarado S, Chavez C, Dick L, Felix R, Johnson D, Chambers CD; Kao; Jones; Alvarado; Chavez; Dick; Felix; Johnson; Chambers (July 2005). "Minor malformations characteristic of the retinoic acid embryopathy and other birth outcomes in children of women exposed to topical tretinoin during early pregnancy". Am J Med Genet A 136 (2): 117–21. doi:10.1002/ajmg.a.30744. PMID 15940677.
- "Vitamin may cure smoking disease". BBC News Online. December 22, 2003. Retrieved 2006-11-18.
- Mao J, Goldin J, Dermand J, Ibrahim G, Brown M, Emerick A, McNitt-Gray M, Gjertson D, Estrada F, Tashkin D, Roth M; Goldin; Dermand; Ibrahim; Brown; Emerick; McNitt-Gray; Gjertson; Estrada; Tashkin; Roth (1 March 2002). "A pilot study of all-trans-retinoic acid for the treatment of human emphysema". Am J Respir Crit Care Med 165 (5): 718–23. doi:10.1164/ajrccm.165.5.2106123. PMID 11874821.
- Roth M, Connett J, D'Armiento J, Foronjy R, Friedman P, Goldin J, Louis T, Mao J, Muindi J, O'Connor G, Ramsdell J, Ries A, Scharf S, Schluger N, Sciurba F, Skeans M, Walter R, Wendt C, Wise R; Connett; d'Armiento; Foronjy; Friedman; Goldin; Louis; Mao; Muindi; O'Connor; Ramsdell; Ries; Scharf; Schluger; Sciurba; Skeans; Walter; Wendt; Wise; Forte Study (2006). "Feasibility of retinoids for the treatment of emphysema study". Chest 130 (5): 1334–45. doi:10.1378/chest.130.5.1334. PMID 17099008.
- Lewin, Anita H.; Whaley, M. Glenn; Parker, Steven R.; Carroll, F. Ivy; Moreland, Charles G. (May 1982). "12-Carboxyretinoic acids. Synthesis and structure". The Journal of Organic Chemistry 47 (10): 1799–1807. doi:10.1021/jo00349a001.
- Houghton Mifflin Harcourt, The American Heritage Dictionary of the English Language, Houghton Mifflin Harcourt.
- Oxford Dictionaries, Oxford Dictionaries Online, Oxford University Press.
- Merriam-Webster, Merriam-Webster's Medical Dictionary, Merriam-Webster.
- Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier.
- "Prescription Medications for Treating Acne". American Academy of Dermatology.
- Prescribing Information for Retin-A Micro Ortho
- Tretinoin AHFS Consumer Medication Information at PubMed Health
- Tretinoin Cream Prescribing Information Drugs.com
- Retin-A Cream, Gel, Liquid Prescribing Information Drugs.com