"ATRA" redirects here. For the 2012 U.S. fiscal cliff, see American Taxpayer Relief Act of 2012. For transit organization, see Advanced Transit Association.
Tretinoin
|
|
| Systematic (IUPAC) name |
| retinoic acid |
| Clinical data |
| Trade names |
Avita, Renova, Retin-a |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a682437 |
| Licence data |
US Daily Med:link |
| Pregnancy cat. |
X (AU) C (US) |
| Legal status |
Prescription Only (S4) (AU) POM (UK) ℞-only (US) |
| Routes |
Topical, oral |
| Pharmacokinetic data |
| Protein binding |
> 95% |
| Half-life |
0.5-2 hours |
| Identifiers |
| CAS number |
N |
| ATC code |
D10AD01 L01XX14 |
| PubChem |
CID 444795 |
| IUPHAR ligand |
2644 |
| DrugBank |
DB00755 |
| ChemSpider |
392618 Y |
| UNII |
5688UTC01R Y |
| KEGG |
D00094 Y |
| ChEBI |
CHEBI:15367 Y |
| ChEMBL |
CHEMBL38 Y |
| Chemical data |
| Formula |
C20H28O2 |
| Mol. mass |
300.4412 g/mol |
SMILES
- O=C(O)\C=C(\C=C\C=C(\C=C\C1=C(\CCCC1(C)C)C)C)C
|
InChI
-
InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14+ Y
Key:SHGAZHPCJJPHSC-YCNIQYBTSA-N Y
|
| Physical data |
| Melt. point |
180 °C (356 °F) |
| N (what is this?) (verify) |
Tretinoin 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.
Contents
- 1 Uses
- 1.1 Dermatology
- 1.2 Leukemia
- 2 Clinical pharmacology
- 3 Side effects
- 3.1 In dermatological use
- 3.2 In leukemia use
- 3.3 Teratogenicity
- 4 Research uses
- 5 Manufacture
- 6 See also
- 7 Footnotes
- 8 External links
Uses
Dermatology
Tretinoin was co-developed by James Fulton and Albert Kligman in 1969.[1] Together, Fulton and Kligman are credited as the inventors of Retin-A.[1] Fulton was a researcher at the University of Pennsylvania at the time.[1] The University of Pennsylvania held the patent for Retin-A, which it licensed to pharmaceutical companies.[1]
Tretinoin is most commonly used as a form of acne treatment.[2] It was the first retinoid developed for this type of topical use.[citation needed] Tretinoin is the best studied retinoid in the treatment of photoaging.[3] It is used by some as a hair loss treatment [4] and is a component of many commercial products that are advertised as being able to slow skin aging or remove wrinkles.[5][6] Topical tretinoin is also used to treat and reduce the appearance of stretch marks by increasing collagen production in the dermis.[7]
Leukemia
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).[8][9]
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.[citation needed] It is usually prescribed for 15 days every three months at about 8–10 10-mg capsules per day.[citation needed]
Clinical pharmacology
Successfully treating acute promyelocytic leukemia (APL) with Tretinoin was a major breakthrough in APL therapy.[10] 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.[11] 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.[citation needed]
Side effects
In dermatological use
|
|
This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (December 2011) |
When used, dryness or increased sensitivity to sunlight of the affected skin may occur.[12] More sensitive patients may also experience redness, scaling, itching, and burning.[13] 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 sunburn;[14] 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.[citation needed] The wax will, when removed, pull off the top level of epithelium (skin) with it, leaving a red, inflamed, sore mark for several days.[citation needed] Tweezing or threading (epilation) is a viable option for hair removal. The recommended timeframe to wait for a waxing treatment after using tretinoin varies from source to source; anywhere from five days to three months have been reported. Patients should consult with their esthetician and dermatologist to discuss the best hair removal options during or after tretinoin use.[citation needed]
In leukemia use
|
|
This section does not cite any references or sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (December 2011) |
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 fetal skull abnormalities in rats.[15] Women who are or may be pregnant, or who are seeking to become pregnant, are therefore warned against using it.[16] 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.[17]
Research uses
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.[18] Studies suggested this might form a promising treatment in human emphysema patients.[19] 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.[20]
Manufacture
Tetrinoin can be synthesized from ionone.[21]
-
See also
- Baldness treatments
- Hypervitaminosis A syndrome
- Talarozole, an experimental drug potentiating the effects of tretinoin
- ^ a b c d "Dr. James Fulton, co-creator of Retin-A and acne researcher, dies". Miami Herald. 2013-07-2013. Retrieved 2013-07-27.
- ^ 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
- ^ How to Use Tretinoin (Retin-A)
- ^ 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 (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 (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 (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.
External links
- "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
|
Acne-treating agents (D10)
|
|
| Antibacterial |
- Azelaic acid
- Benzoyl peroxide#
- Hydroxyquinoline
- Blue light therapy
- Tea tree oil
|
|
| Keratolytic |
- Glycolic acid
- Salicylic acid#
- Sulfur
- Benzoyl peroxide#
|
|
| Anti-inflammatory |
- Nicotinamide
- Ibuprofen #
- Aspirin #
- Red light therapy
|
|
| Antibiotics |
- Clindamycin
- Dapsone
- Erythromycin
- Sulfacetamide
- Tetracyclines (Lymecycline
- Minocycline
- Doxycycline)
|
|
| Hormonal |
- Antiandrogens
- Contraceptives
|
|
| Retinoids |
- Adapalene
- Isotretinoin
- Motretinide
- Tazarotene
- Tretinoin
|
|
| Other |
- Benzamycin
- Epristeride
- Mesulfen
- Pelretin
- Stridex
- Tioxolone
|
|
| Combinations |
- Adapalene/benzoyl peroxide
- Benzoyl peroxide/clindamycin
- Clindamycin/tretinoin
- Erythromycin/isotretinoin
- Sulfacetamide/sulfur
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
|
|
|
|
noco/cong/tumr, sysi/epon
|
|
|
|
|
|
Vitamins (A11)
|
|
| Fat soluble |
|
A
|
α-Carotene · β-Carotene · Retinol# · Tretinoin
|
|
|
D
|
D2 (Ergosterol, Ergocalciferol#) · D3 (7-Dehydrocholesterol, Previtamin D3, Cholecalciferol, 25-hydroxycholecalciferol, Calcitriol (1,25-dihydroxycholecalciferol), Calcitroic acid) · D4 (Dihydroergocalciferol) · D5 · D analogues (Alfacalcidol, Dihydrotachysterol, Calcipotriol, Tacalcitol, Paricalcitol)
|
|
|
E
|
Tocopherol (Alpha, Beta, Gamma, Delta) · Tocotrienol (Alpha, Beta, Gamma, Delta) · Tocofersolan
|
|
|
K
|
Naphthoquinone · Phylloquinone (K1) · Menaquinones (K2) · Menadione (K3)‡ · Menadiol (K4)
|
|
|
| Water soluble |
|
B
|
B1 (Thiamine#) · B2 (Riboflavin#) · B3 (Niacin, Nicotinamide#) · B5 (Pantothenic acid, Dexpanthenol, Pantethine) · B6 (Pyridoxine#, Pyridoxal phosphate, Pyridoxamine) · B7 (Biotin) · B9 (Folic acid, Dihydrofolic acid, Folinic acid, L-methylfolate) · B12 (Cyanocobalamin, Hydroxocobalamin, Methylcobalamin, Cobamamide) · Choline
|
|
|
C
|
Ascorbic acid# · Dehydroascorbic acid
|
|
|
| Combinations |
Multivitamins
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
|
|
|
|
noco, nuvi, sysi/epon, met
|
|
|
|
|
|
Carotenoids
|
|
| Carotenes (C40) |
- α-Carotene
- β-Carotene
- γ-Carotene
- δ-Carotene
- ε-Carotene
- ζ-Carotene
- Lycopene
- Neurosporene
- Phytoene
- Phytofluene
- Torulene
- Lycopersene
|
|
| Xanthophylls (C40) |
- Antheraxanthin
- Astaxanthin
- Canthaxanthin
- Citranaxanthin
- Cryptoxanthin
- Diadinoxanthin
- Diatoxanthin
- Dinoxanthin
- Flavoxanthin
- Fucoxanthin
- Lutein
- Neoxanthin
- Rhodoxanthin
- Rubixanthin
- Violaxanthin
- Zeaxanthin
|
|
| Apocarotenoids (C<40) |
- Abscisic acid
- Apocarotenal
- Bixin
- Crocetin
- Food orange 7
- Ionones
- Peridinin
|
|
| Vitamin A retinoids (C20) |
- Retinal
- Retinoic acid
- Retinol
|
|
| Retinoid drugs |
- Acitretin
- Alitretinoin
- Bexarotene
- Etretinate
- Fenretinide
- Isotretinoin
- Tazarotene
- Tretinoin
|
|
