Tretinoin 637902 224470749 2008-07-08T23:58:59Z 71.224.213.113 {{drugbox | IUPAC_name = 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl) -nona-2,4,6,8-tetraenoic acid | image = Retinoic_acid.png | width = 350 | CAS_number = 302-79-4 | ATC_prefix = D10 | ATC_suffix = AD01 | ATC_supplemental = {{ATC|L01|XX14}} | PubChem = 5538 | DrugBank = APRD00362 | C=20 | H=28 | O=2 | | molecular_weight = 300.4412 g/mol | bioavailability = | protein_bound = > 95% | melting_point=180 | metabolism = | elimination_half-life = 0.5-2 hours | pregnancy_category = C(topical), D(oral) | legal_status = | legal_AU = S4 | routes_of_administration = Topical, oral }} '''Tretinoin''' is the acid form of [[vitamin A]] and so also known as '''all-trans retinoic acid''' or '''ATRA'''. It is a drug commonly used to treat [[acne vulgaris]] and [[keratosis pilaris]]. It is available as a cream or gel (brand names '''Renova''', '''Retin-A'''). It is also used to treat [[acute promyelocytic leukemia]] (APML) which is sold for this indication by [[Roche]] under the brand name '''Vesanoid'''. ==Uses== ===Dermatology=== Tretinoin is most commonly used as a form of acne treatment.<ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682437.html MedlinePlus Drug Information: Tretinoin<!-- Bot generated title -->]</ref> It was the first [[retinoid]] developed for this type of topical use. Tretinoin is the best studied retinoid in the treatment of photoaging.<ref>{{cite journal| title=Topical retinoids in the treatment of photoaging| year=2005| month=Jun| pmid=17166212| author=Stefanaki C, Stratigos A, Katsambas A| journal= J Cosmet Dermatol| volume=4(2)| pages=130–4| doi=10.1111/j.1473-2165.2005.40215.x}}</ref> It is used by some as a hair loss treatment and also a component of many commercial products that are advertised as being able to slow skin aging or remove wrinkles.<ref>[http://www.farrellmanual.com/topical/retina.htm Retin-A, Tretinoin as a hair loss treatment<!-- Bot generated title -->]</ref> [[Topical]] tretinoin is also used to [[treatment|treat]] and reduce the appearance of [[stretch marks]] by increasing [[collagen]] production in the [[dermis]].<ref>{{cite web |url = http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=633&sectionId=11 |title = Stretch marks - treatment |accessdate = 2007-06-28 |date = 2007-06-27 |work = NHS Direct - Health encyclopaedia |publisher = NHS Direct Online }}</ref> ===Leukemia=== In addition, tretinoin (marketed as Vesanoid) is also used to treat at least one form of cancer ([[acute promyelocytic leukemia]] (APML), also called [[acute myeloid leukemia]] subtype M3), usually together with other drugs, by causing the immature blood cells to differentiate (i.e. mature) and die.<!-- --><ref>{{cite journal | author = Huang M, Ye Y, Chen S, Chai J, Lu J, Zhoa L, Gu L, Wang Z | title = Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia | journal = Blood | volume = 72 | issue = 2 | pages = 567–72 | year = 1988 | pmid = 3165295| url=http://www.bloodjournal.org/cgi/reprint/72/2/567.pdf | format=PDF}} - [http://www.bloodjournal.org/cgi/content/abstract/72/2/567 Abstract]</ref><!-- --><ref>{{cite journal | author = Castaigne S, Chomienne C, Daniel M, Ballerini P, Berger R, Fenaux P, Degos L | title = All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results | journal = Blood | volume = 76 | issue = 9 | pages = 1704–9 | year = 1990 | pmid = 2224119 | url=http://www.bloodjournal.org/cgi/reprint/76/9/1704.pdf | format=PDF}}</ref> 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 over 3 months at about 8 capsules per day. ==Clinical pharmacology== Its success in treating acute promyelocytic leukemia was a major breakthrough in the treatment of this type of leukemia.<!-- --><ref>{{cite journal | author = Sanz M | title = Treatment of acute promyelocytic leukemia | journal = Hematology Am Soc Hematol Educ Program | volume = 2006| issue = | pages = 147–55 | year =2006 | pmid = 17124054 | url=http://www.asheducationbook.org/cgi/content/full/2006/1/147 | doi = 10.1182/asheducation-2006.1.147}}</ref> It works in APML because the majority of cases involve a chromosomal translocation of [[chromosome]]s 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 [[promyelocyte]]s to differentiate to normal mature blood cells. ==Side effects== ===In dermatological use=== When used, dryness 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. This product increases the risk of extreme sunburn; care should be taken (shade, [[sunscreen]], etc.) to protect treated skin from overexposure to ultraviolet light. Because usage of tretinoin may cause thinning of the skin, it is strongly recommended that patients who are using the drug abstain from hair removal waxing. The wax will, when removed, pull off the top level of epithelium (skin) with it, leaving a red, inflamed, sore, and unattractive mark for several days. Tweezing or [[threading (epilation)]] is a viable option for hair removal while using tretinoin. The recommended timeframe to wait for a waxing treatment after using tretinoin varies from source to source; anywhere from 5 days to 3 months have been reported. Patients should consult with their aesthetician and dermatologist to discuss the best hair removal options during or after tretinoin use. ===In leukemia use=== 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. ===Teratogenicity=== It is a [[teratogen]], and therefore can cause birth defects and tests have shown increases in foetal skull abnormalities in rats. Women who are or may be pregnant, or who are seeking to become pregnant, are therefore warned against using it.<ref>[http://www.drugs.com/cdi/tretinoin.html Tretinoin facts and comparsions at Drugs.com<!-- Bot generated title -->]</ref> This teratogenic effect is caused by the interference of the exogenous retinoic acid with endogenous [[Retinol|retinoic acid]] signaling, which plays a role in patterning the developing embryo. However the risks of topical tretinoin to the unborn child seems to be limited.<ref>{{cite journal| title=Minor malformations characteristic of the retinoic acid embryopathy and other birth outcomes in children of women exposed to topical tretinoin during early pregnancy| year=2005| month=Jul| pmid=15940677| author=Loureiro KD, Kao KK, Jones KL, Alvarado S, Chavez C, Dick L, Felix R, Johnson D, Chambers CD| journal= Am J Med Genet A| volume=136(2)| pages=117–21| doi=10.1002/ajmg.a.30744}}</ref> ==Research uses== A study published by the European Respiratory Journal in 2002 suggested that tretinoin can reverse the effects of emphysema in mice by returning elasticity (and regenerating lung tissue through gene mediation) to the alveoli.<!-- --><ref>{{cite news | title=Vitamin may cure smoking disease | url=http://news.bbc.co.uk/2/hi/health/3329103.stm | date=[[December 22]], [[2003]] | publisher=BBC News | accessdate=2006-11-18}}</ref> Studies suggested that this might form a promising treatment in human emphysema patients,<!-- --><ref>{{cite journal | author = Mao J, Goldin J, Dermand J, Ibrahim G, Brown M, Emerick A, McNitt-Gray M, Gjertson D, Estrada F, Tashkin D, Roth M | title = A pilot study of all-trans-retinoic acid for the treatment of human emphysema | journal = Am J Respir Crit Care Med | volume = 165 | issue = 5 | pages = 718–23 | year = 2002 | pmid = 11874821 | url=http://ajrccm.atsjournals.org/cgi/content/full/165/5/718}}</ref> 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 that further research is needed to reach conclusions on this treatment.<!-- --><ref>{{cite journal | author = 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 | title = Feasibility of retinoids for the treatment of emphysema study | journal = Chest | volume = 130 | issue = 5 | pages = 1334–45 | year = 2006 | pmid = 17099008 | url=http://www.chestjournal.org/cgi/content/full/130/5/1334 | doi = 10.1378/chest.130.5.1334}}</ref> ==See also== *[[Baldness treatments]] *[[Hypervitaminosis A syndrome]] ==Footnotes== <div class="references-small"><references/></div> ==External links== *[http://health.yahoo.com/drug/d01244a1 Thomson MicroMedix listing for Tretinoin Topical] *[http://www.pharma-solutions.basf.com/(3wb2dv2sbs4ccp5554h1vx55)/pdf/statements/Technical%20Information/Pharma%20Solutions/Tretinoin.pdf BASF Technical Information] *{{cite web | title=Prescription Medications for Treating Acne | publisher=American Academy of Dermatology | url=http://www.skincarephysicians.com/acnenet/prescriptmeds.html | accessdate=2006-07-15}} {{Acne Agents}} {{Chemotherapeutic agents}} {{Vitamin}} [[Category:Carotenoids]] [[Category:Carboxylic acids]] [[Category:Chemotherapeutic agents]] [[Category:Dermatological preparations]] [[Category:Retinoids]] [[Category:Hair loss]] [[de:Tretinoin]] [[fr:Trétinoïne]] [[ja:トレチノイン]] [[pl:Tretynoina]] [[zh:維A酸]]