Tretinoin

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Tretinoin
Tretinoin structure.svg
Clinical data
Pronunciation See pronunciation note
Trade names Vesanoid, Avita, Renova, Retin-a, others
AHFS/Drugs.com Monograph
MedlinePlus a682437
License data
Pregnancy
category
  • AU: X (High risk)
  • US: C (Risk not ruled out)
Routes of
administration
topical, by mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Protein binding > 95%
Biological half-life 0.5-2 hours
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.005.573
Chemical and physical data
Formula C20H28O2
Molar mass 300.4412 g/mol
3D model (JSmol)
Melting point 180 °C (356 °F)
  (verify)

Tretinoin, also known as all-trans retinoic acid (ATRA), is medication used for the treatment of acne and acute promyelocytic leukemia.[1][2][3] For acne it is applied to the skin as a cream or ointment.[3] For leukemia it is taken by mouth for up to three months.[1]

Common side effects when used by mouth include shortness of breath, headache, numbness, depression, skin dryness, itchiness, hair loss, vomiting, muscle pains, and vision changes.[1] Other severe side effects include high white blood cell counts and blood clots.[1] When used as a cream side effects include skin redness, peeling, and sun sensitivity.[3] Use during pregnancy is known to harm the baby.[1] It is in the retinoid family of medications.[2]

Tretinoin was patented in 1957 and approved for medical use in 1962.[4] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[5] Tretinoin is available as a generic medication.[6] In the United Kingdom the cream together with erythromycin costs the NHS about £7.05 per 25 mL while the pills are £1.61 per 10 mg.[3]

Medical uses[edit]

Skin use[edit]

Tretinoin is most commonly used to treat acne.[7] It is also used off-label to treat and reduce the appearance of stretch marks by increasing collagen production in the dermis.[8]

In topical form, this drug is pregnancy category C and should not be used by pregnant women.[7]

People using the topical form should not also use any cream or lotion that has a strong drying effect, contains alcohol, astringents, spices, lime, sulfur, resorcinol, or aspirin, as these may interact with tretinoin or exacerbate its side effects.[7]

Leukemia[edit]

Tretinoin is used to induce remission in people with acute promyelocytic leukemia who have a mutation (the t(15;17) translocation 160 and/or the presence of the PML/RARα gene) and who don't respond to anthracyclines or can't take that class of drug. It is not used for maintenance therapy.[9][10][11]

In oral form, this drug is pregnancy category D and should not be used by pregnant women as it may harm the fetus.[9]

Side effects[edit]

Skin use[edit]

Topical tretinoin is only for use on skin and it should not be applied to eyes or mucosal tissues. Common side effects include skin irritation, redness, swelling, and blistering.[7]

Leukemia use[edit]

The oral form of the drug has boxed warnings concerning the risks of retinoic acid syndrome and leukocytosis.[9]

Other significant side effects include a risk of thrombosis, benign intracranial hypertension in children, high lipids (hypercholesterolemia and/or hypertriglyceridemia), and liver damage.[9]

There are many significant side effects from this drug that include malaise (66%), shivering (63%), hemorrhage (60%), infections (58%), peripheral edema (52%), pain (37%), chest discomfort (32%), edema (29%), disseminated intravascular coagulation (26%), weight increase (23%), injection site reactions (17%), anorexia (17%), weight decrease (17%), and myalgia (14%).[9]

Respiratory side effects usually signify retinoic acid syndrome, and include upper respiratory tract disorders (63%), dyspnea (60%), respiratory insufficiency (26%), pleural effusion (20%), pneumonia (14%), rales (14%), and expiratory wheezing (14%), and many others at less than 10%.[9]

Around 23% of people taking the drug have reported eararche or a feeling of fullness in their ears.[9]

Gastrointestinal disorders include bleeding (34%), abdominal pain (31%), diarrhea (23%), constipation (17%), dyspepsia (14%), and swollen belly (11%) and many others at less than 10%.[9]

In the cardiovascular system, side effects include arrhythmias (23%), flushing (23%), hypotension (14%), hypertension (11%), phlebitis (11%), and cardiac failure (6%) and for 3% of patients: cardiac arrest, myocardial infarction, enlarged heart, heart murmur, ischemia, stroke, myocarditis, pericarditis, pulmonary hypertension, secondary cardiomyopathy.[9]

In the nervous system, side effects include dizziness (20%), paresthesias (17%), anxiety (17%), insomnia (14%), depression (14%), confusion (11%), and many others at less than 10% frequency.[9]

In the urinary system, side effects include renal insufficiency (11%) and several others at less than 10% frequency.[9]

Mechanism of action[edit]

For its use in cancer, its mechanism of action is unknown, but on a cellular level, laboratory test 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.[9] Recent study shows that ATRA inhibits and degrades active PIN1.[12]

For its use in acne, the mechanism is unknown, but again on a cellular level there is evidence that it decreases the ability of epithelial cells in hair follicles to stick together, leading to fewer blackheads; it also seems to make the epithelial cells divide faster, causing the blackheads to be pushed out.[7]

History[edit]

Tretinoin was co-developed for its use in acne by James Fulton and Albert Kligman when they were at University of Pennsylvania in the late 1960s.[13][14] The University of Pennsylvania held the patent for Retin-A, which it licensed to pharmaceutical companies.[14]

Etymology[edit]

The origin of the name tretinoin is uncertain,[15][16] although several sources agree (one with probability,[15] one with asserted certainty[17]) that it probably comes from trans- + retinoic [acid] + -in, which is plausible given that tretinoin is the all-trans isomer of retinoic acid. The name isotretinoin is the same root tretinoin plus the prefix iso-. Regarding pronunciation, the following variants apply equally to both tretinoin and isotretinoin. Given that retinoic is pronounced /ˌrɛtɪˈnɪk/,[16][17][18][19] it is natural that /ˌtrɛtɪˈnɪn/ is a commonly heard pronunciation. Dictionary transcriptions also include /ˌtrɪˈtɪnɪn/ (tri-TIN-oh-in)[16][18] and /ˈtrɛtɪnɔɪn/.[17][19]

Research[edit]

Tretinoin has been explored as a treatment for hair loss, potentially as a way to increase the ability of minoxidil to penetrate the scalp, but the evidence is weak and contradictory.[20][21]

See also[edit]

References[edit]

  1. ^ a b c d e "Tretinoin". The American Society of Health-System Pharmacists. Archived from the original on 30 November 2016. Retrieved 8 December 2016. 
  2. ^ a b Tivnan, Amanda (2016). Resistance to Targeted Therapies Against Adult Brain Cancers. Springer. p. 123. ISBN 9783319465050. Archived from the original on 2017-11-05. 
  3. ^ a b c d British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. pp. 627, 821–822. ISBN 9780857111562. 
  4. ^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 476. ISBN 9783527607495. Archived from the original on 2017-11-05. 
  5. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016. 
  6. ^ "Tretinoin topical". The American Society of Health-System Pharmacists. Archived from the original on 16 May 2016. Retrieved 8 December 2016. 
  7. ^ a b c d e Topical Cream Gel Liquid Label Archived 2011-12-29 at the Wayback Machine.
  8. ^ Arthur W. Perry (2007). Straight talk about cosmetic surgery. Yale University Press. p. 63. ISBN 978-0-300-12104-9. 
  9. ^ a b c d e f g h i j k l Oral Label Archived 2016-05-08 at the Wayback Machine.
  10. ^ 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" (PDF). Blood. 72 (2): 567–72. PMID 3165295. 
  11. ^ 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" (PDF). Blood. 76 (9): 1704–9. PMID 2224119. 
  12. ^ Wei, Shuo; Kozono, Shingo; Kats, Lev; Nechama, Morris; Li, Wenzong; Guarnerio, Jlenia; Luo, Manli; You, Mi-Hyeon; Yao, Yandan (May 2015). "Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer". Nature Medicine. 21 (5): 457–466. doi:10.1038/nm.3839. ISSN 1546-170X. 
  13. ^ Vivant Pharmaceuticals, LLC Press Release. July 10, 2013, Vivant Skin Care Co-founder James E. Fulton, MD, Loses Colon Cancer Battle
  14. ^ a b Denis Gellene for the New York Times. Feb 22, 2010. Dr. Albert M. Kligman, Dermatologist, Dies at 93 Archived 2017-11-05 at the Wayback Machine.
  15. ^ a b Merriam-Webster, Merriam-Webster's Unabridged Dictionary, Merriam-Webster. 
  16. ^ a b c Oxford Dictionaries, Oxford Dictionaries Online, Oxford University Press, archived from the original on 2014-10-22. 
  17. ^ a b c Houghton Mifflin Harcourt, The American Heritage Dictionary of the English Language, Houghton Mifflin Harcourt, archived from the original on 2015-09-25. 
  18. ^ a b Merriam-Webster, Merriam-Webster's Medical Dictionary, Merriam-Webster. 
  19. ^ a b Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier. 
  20. ^ Ralph M. Trüeb. The Difficult Hair Loss Patient: Guide to Successful Management of Alopecia and Related Conditions. Springer, 2015. ISBN 9783319197012 Pg. 95 Archived 2017-11-05 at the Wayback Machine.
  21. ^ Rogers, N; 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. 

External links[edit]