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{{Chembox new
{{DrugProjectFormSinglePage
| ImageFile = Retinol structure.svg
|authorTag={{Ammu}}
| ImageSize = 250px
|genericName=retinol
| IUPACName =(2E,4E,6E,8E)-3,7-dimethyl- 9-(2,6,6-trimethylcyclohex-1-enyl)
|aOrAn=a
nona-2,4,6,8-tetraen-1-ol
|drugClass=[[vitamin]] analog
| OtherNames =  
|indicationType=treatment
| Section1 = {{Chembox Identifiers
|indication=[[acne vulgaris]]
|   CASNo = 11103-57-4
|adverseReactions=[[hypopigmentation]], [[hyperpigmentation]], skin [[erythema]]
|   PubChem = 1071
|blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
|   SMILES = CC(=CC=CC(C)=CCO) C=CC1=C(C)CCCC1(C)C
|blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
|  MeSHName =
  }}
| Section2 = {{Chembox Properties
|   Formula = C<sub>20</sub>H<sub>30</sub>O
|  MolarMass = 286.456 g/mol
|  Appearance =
|  Density =
|  MeltingPt =
|  BoilingPt =
  }}
| Section3 = {{Chembox Hazards
|  Solubility =
|  MainHazards =
|  FlashPt =
|  Autoignition =
  }}
}}
{{CMG}}
__NOTOC__


* Content


'''Retinol (Afaxin)''', the animal form of [[vitamin A]], is a fat-soluble vitamin important in [[visual system|vision]] and [[bone]] growth. It belongs to the family of chemical compounds known as [[retinoid]]s.
<!--Adult Indications and Dosage-->
Retinol is ingested in a precursor form; animal sources ([[liver]] and [[Egg (food)|egg]]s) contain retinyl [[ester]]s, whereas [[plant]]s ([[carrot]]s, [[spinach]]) contain pro-vitamin A [[carotenoid]]s. Hydrolysis of retinyl esters results in retinol while pro-vitamin A carotenoids can be cleaved to produce [[retinal]]. Retinal, also known as retinaldehyde, can be reversibly reduced to produce retinol or it can be irreversibly oxidized to produce retinoic acid. The best described active retinoid metabolites are 11-''cis''-retinal and the all-trans and 9-cis-isomers of retinoic acid.


==Discovery==
<!--FDA-Labeled Indications and Dosage (Adult)-->
In 1913, [[Elmer McCollum]], a [[biochemist]] at the [[University of Wisconsin-Madison]], and colleague [[Marguerite Davis]] identified a fat-soluble nutrient in [[butterfat]] and [[cod liver oil]]. Their work confirmed that of [[Thomas Osborne (biochemist)|Thomas Osborne]] and [[Lafayette Mendel]], at [[Yale University|Yale]], which suggested a fat-soluble nutrient in butterfat, also in 1913.<ref name=Semba>Semba RD. Vitamin A as "Anti-Infective" Therapy, 1920–1940. Journal of Nutrition. 1999;129:783-791. PMID 10203551. [http://www.nutrition.org/cgi/content/full/129/4/783 Full Text Available]</ref> Vitamin A was first synthesized in 1947 by two Dutch chemists, [[David Adriaan van Dorp]] and Jozef Ferdinand Arens.
|fdaLIADAdult=* RETIN-A is indicated for topical application in the treatment of [[acne vulgaris]]. The safety and efficacy of the long-term use of this product in the treatment of other disorders have not been established.
* RETIN-A Gel, Cream or Liquid should be applied once a day, before retiring, to the skin where acne lesions appear, using enough to cover the entire affected area lightly. Liquid: The liquid may be applied using a fingertip, gauze pad, or cotton swab. If gauze or cotton is employed, care should be taken not to oversaturate it to the extent that the liquid would run into areas where treatment is not intended. Gel: Excessive application results in “pilling” of the gel, which minimizes the likelihood of over application by the patient.
* Application may cause a transitory feeling of warmth or slight stinging. In cases where it has been necessary to temporarily discontinue therapy or to reduce the frequency of application, therapy may be resumed or frequency of application increased when the patients become able to tolerate the treatment.
* Alterations of vehicle, drug concentration, or dose frequency should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.
* During the early weeks of therapy, an apparent exacerbation of inflammatory lesions may occur. This is due to the action of the medication on deep, previously unseen lesions and should not be considered a reason to discontinue therapy.
* Therapeutic results should be noticed after two to three weeks but more than six weeks of therapy may be required before definite beneficial effects are seen.
* Once the acne lesions have responded satisfactorily, it may be possible to maintain the improvement with less frequent applications, or other dosage forms.
* Patients treated with RETIN-A ([[tretinoin]]) acne treatment may use cosmetics, but the area to be treated should be cleansed thoroughly before the medication is applied.
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.


==Chemical structure and function==
<!--Non–Guideline-Supported Use (Adult)-->
Many different geometric isomers of retinol, retinal and retinoic acid are possible as a result of either a ''[[trans]]'' or ''[[cis]]'' configuration of four of the five [[double bond]]s found in the [[polyene]] chain. The ''cis'' isomers are less stable and can readily convert to the all-''trans'' configuration (as seen in the structure of all-''trans''-retinol shown here). Nevertheless, some ''cis'' isomers are found naturally and carry out essential functions. For example, the 11-''cis''-retinal isomer is the [[chromophore]] of [[rhodopsin]], the [[vertebrate]] [[photoreceptor]] molecule. Rhodopsin is comprised of the 11-cis-retinal covalently linked via a [[Schiff base]] to the [[opsin]] protein (either rod opsin or blue, red or green cone opsins). The process of vision relies on the light-induced isomerisation of the chromophore from 11-''cis'' to all-''trans'' resulting in a change of the conformation and activation of the photoreceptor molecule. One of the earliest signs of vitamin A deficiency is night-blindness followed by decreased visual acuity.  
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.


[[George Wald]] won the [[1967]] [[Nobel Prize in Physiology or Medicine]] for his work with [[retina]] pigments (also called visual pigments), which led to the understanding of the role of vitamin A in vision.
<!--Pediatric Indications and Dosage-->


Many of the non-visual functions of vitamin A are mediated by retinoic acid, which regulates gene expression by activating intracellular [[retinoic acid receptor]]s. The non-visual functions of vitamin A are essential in the immunological function, reproduction and embryonic development of vertebrates as evidenced by the impaired growth, susceptibility to infection and birth defects observed in populations receiving suboptimal vitamin A in their diet.
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.


===Role in embryology===<!-- This section is linked from [[Postpartum depression]] -->
<!--Off-Label Use and Dosage (Pediatric)-->
Retinoic acid via the retinoic acid receptor influences the process of cell differentiation, hence, the growth and development of embryos. During development there is a concentration gradient of retinoic acid along the anterior-posterior (head-tail) axis. Cells in the embryo respond differently to retinoic acid depending on the amount present. For example, in vertebrates the hindbrain transiently forms eight rhombomers and each rhombomere has a specific pattern of genes being expressed. If retinoic acid is not present the last four rhombomeres do not develop. Instead rhombomeres 1-4 grow to cover the same amount of space as all eight would normally occupy. Retinoic acid has its effects by turning on a differential pattern of Hox genes which encode different homeodomain transcription factors which in turn can turn on cell type specific genes. Deletion of the Hox-1 gene from rhombomere 4 makes the neurons growing in that region behave like neurons from rhombomere 2. The retina is also patterned by retinoic acid, with a concentration gradient that is high on the ventral side of the retina and low on the dorsal side.


===Stem cell biology===
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.


Retinoic acid is an influential factor used in [[differentiation]] of stem cells to more committed fates, echoing retinoic acid's importance in natural embryonic developmental pathways. It is thought to initiate differentiation into a number of different cell lineages by unsequestering certain sequences in the genome.  
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.


It has numerous applications in a plethora of stem cell differentiation protocols; amongst these are the differentiation of human [[embryonic stem cell]]s to posterior foregut lineages and also to functional [[motor neuron]]s.
<!--Contraindications-->
|contraindications=* Use of the product should be discontinued if hypersensitivity to any of the ingredients is noted.
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
|postmarketing=* The skin of certain sensitive individuals may become excessively red, edematous, blistered, or crusted. If these effects occur, the medication should either be discontinued until the integrity of the [[skin]] is restored, or the medication should be adjusted to a level the patient can tolerate. True contact [[allergy]] to topical tretinoin is rarely encountered.
* Temporary hyper or [[hypopigmentation]] has been reported with repeated application of RETIN-A. Some individuals have been reported to have heightened susceptibility to sunlight while under treatment with RETIN-A. To date, all adverse effects of RETIN-A have been reversible upon discontinuance of therapy
|FDAPregCat=C
|useInPregnancyFDA=* Oral tretinoin has been shown to be teratogenic in rats when given in doses 1000 times the topical human dose. Oral tretinoin has been shown to be fetotoxic in rats when given in doses 500 times the topical human dose.
* Topical tretinoin has not been shown to be teratogenic in rats and rabbits when given in doses of 100 and 320 times the topical human dose, respectively (assuming a 50 kg adult applies 250 mg of 0.1% cream topically). However, at these topical doses, delayed ossification of a number of bones occurred in both species. These changes may be considered variants of normal development and are usually corrected after weaning. There are no adequate and well-controlled studies in pregnant women. Tretinoin should be used during pregnancy only if the potential benefit justifies the potential risk to the [[fetus]].
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''


===Vision===
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
{{Main|visual cycle}}
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
Vitamin A is required in the production of [[rhodopsin]], the [[visual pigment]] used in low light levels. This is why eating foods rich in vitamin A is said to allow an individual to see in the dark.
|useInNursing=* It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when RETIN-A is administered to a nursing woman.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.


===Epithelial Cells===
<!--Administration and Monitoring-->
Vitamin A is essential for the correct functioning of [[epithelial cells]]. In Vitamin A deficiency, [[mucus-secreting cells]] are replaced by [[keratin]] producing cells, leading to [[xerosis]].  
|administration=* [[Oral]]
* [[Topical]]
|monitoring=* Alterations of vehicle, drug concentration, or dose frequency should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.


===Glycoprotein synthesis===
<!--Overdosage-->
[[Glycoprotein]] synthesis requires adequate Vitamin A status. In severe Vitamin A deficiency, lack of glycoproteins may lead to corneal ulcers or liquefaction.  
|overdose=* If medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur. Oral ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of [[Vitamin A]]
|drugBox={{chembox2
| verifiedrevid = 464381333
| ImageFile =All-trans-Retinol2.svg
| ImageSize = 250px
| ImageName = Retinol
| ImageFile2 = Retinol mol 3D.png
| ImageSize2 = 200px
| ImageName2 = Stick model of retinol
| ImageFile3 = Retinol 3D ball.png
| ImageSize3 = 200px
| ImageName3 = Ball model of retinol
| IUPACName =(2''E'',4''E'',6''E'',8''E'')-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraen-1-ol
| OtherNames =
| Section1 = {{Chembox Identifiers
|  ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 393012
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 81G40H8B0T
| InChI1 = 1/C20H30O/c1-16(8-6-9-17(2)13-15-21)11-12-19-18(3)10-7-14-20(19,4)5/h6,8-9,11-13,21H,7,10,14-15H2,1-5H3/b9-6+,12-11+,16-8+,17-13+
| InChIKey1 = FPIPGXGPPPQFEQ-OVSJKPMPBW
| CASNo = 68-26-8
| CASNo_Ref = {{cascite|correct|CAS}}
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 986
| PubChem = 1071
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17336
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C20H30O/c1-16(8-6-9-17(2)13-15-21)11-12-19-18(3)10-7-14-20(19,4)5/h6,8-9,11-13,21H,7,10,14-15H2,1-5H3/b9-6+,12-11+,16-8+,17-13+
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FPIPGXGPPPQFEQ-OVSJKPMPSA-N
| SMILES = OC/C=C(/C=C/C=C(/C=C/C1=C(/CCCC1(C)C)C)C)C
| MeSHName =
| ATCCode_prefix = A11
| ATCCode_suffix = CA01
| ATC_Supplemental = {{ATC|D10|AD02}}, {{ATC|R01|AX02}}, {{ATC|S01|XA02}}
  }}
| Section2 = {{Chembox Properties
|  C=20|H=30|O=1
|  Appearance =
|  Density =
|  MeltingPt =
|  BoilingPt =
  }}
| Section3 = {{Chembox Hazards
|  Solubility =
|  MainHazards =
|  FlashPt =
|  Autoignition =
  }}
}}
|mechAction=* Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of [[follicular epithelial cells]] with decreased microcomedo formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of [[follicular epithelial cells]] causing extrusion of the [[comedone]].


===Immune System===
<!--Structure-->
Vitamin A is essential to maintain intact [[epithelial tissue]]s as a physical barrier to infection; it is also involved in maintaining a number of immune cell types from both the innate and acquired immune systems. These include the [[lymphocytes]] ([[B-cells]], [[T-cells]], and [[natural killer cells]]), as well as many myelocytes ([[neutrophils]], [[macrophages]], and myeloid [[dendritic cells]]).
|structure=* RETIN-A Gel, Cream and Liquid, containing tretinoin are used for the topical treatment of [[acne vulgaris]]. RETIN-A Gel contains tretinoin (retinoic acid, vitamin A acid) in either of two strengths, 0.025% or 0.01% by weight, in a gel vehicle of butylated hydroxytoluene, hydroxypropyl cellulose and alcohol (denatured with tert-butyl alcohol and brucine sulfate) 90% w/w. RETIN-A (tretinoin) Cream contains tretinoin in either of three strengths, 0.1%, 0.05%, or 0.025% by weight, in a hydrophilic cream vehicle of stearic acid, isopropyl myristate, polyoxyl 40 stearate, stearyl alcohol, xanthan gum, sorbic acid, butylated hydroxytoluene, and purified water. RETIN-A Liquid contains tretinoin 0.05% by weight, polyethylene glycol 400, butylated hydroxytoluene and alcohol (denatured with tert-butyl alcohol and brucine sulfate) 55%. Chemically, tretinoin is all-trans-retinoic acid and has the following structure:
: [[File:Retinol 01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]


===Formation of red blood cells (Haematopoiesis)===
<!--Pharmacodynamics-->
Vitamin A may be needed for normal [[haematopoiesis]]; deficiency causes abnormalities in [[iron metabolism]].
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.


===Growth===
<!--Pharmacokinetics-->
Vitamin A affects the production of [[Growth hormone|human growth hormone]].
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.


==Clinical use==
<!--Nonclinical Toxicology-->
{{main|Tretinoin}}
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
All retinoid forms of vitamin A are used in cosmetic and medical applications applied to the skin. Retinoic acid, termed  [[Tretinoin]] in clinical usage, is used in the treatment of [[Acne vulgaris|acne]] and [[keratosis pilaris]] in a topical cream. An isomer of tretinoin, [[isotretinoin]] is also used orally (under the trade names ''[[Accutane]]'' and ''Roaccutane''), generally for severe or recalcitrant acne.


In cosmetics, vitamin A derivatives are used as [[Anti-aging cream|anti-aging]] chemicals- vitamin A is absorbed through the skin and increases the rate of skin turnover, and gives an increase in [[collagen]] giving a more youthful appearance<ref>[http://archderm.ama-assn.org/cgi/content/abstract/143/5/606 Archives of Dermatology]</ref>
<!--Clinical Studies-->
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.


Tretinoin, under the alternative name of '''all-trans retinoic acid''' (ATRA), is used as chemotherapy for [[acute promyelocytic leukemia]], a subtype of [[acute myelogenous leukemia]]. This is because cells of this subtype of leukemia are sensitive to agonists of the retinoic acid receptors (RARs).
<!--How Supplied-->
|howSupplied=: [[File:Retinol 02.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
|storage=* RETIN-A Liquid, 0.05%, and RETIN-A Gel, 0.025% and 0.01%: store below 86°F. RETIN-A Cream, 0.1%, 0.05%, and 0.025%: store below 80°F.
|packLabel=[[File:Retinol 03.jpg|thumb|none|400px|This image is provided by the National Library of Medicine.]]
[[File:Retinol 04.jpg|thumb|none|400px|This image is provided by the National Library of Medicine.]]
[[File:Retin 05.jpg|thumb|none|400px|This image is provided by the National Library of Medicine.]]
[[File:Retin 03.jpg|thumb|none|400px|This image is provided by the National Library of Medicine.]]
[[File:Retin 04.jpg|thumb|none|400px|This image is provided by the National Library of Medicine.]]
[[File:DailyMed - RETIN-A - tretinoin cream  RETIN-A - tretinoin gel  .png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.


==Units of measurement==
<!--Precautions with Alcohol-->
When referring to dietary allowances or [[nutrition]]al science, retinol is usually measured in [[international unit]]s (IU). IU refers to biological activity and therefore is unique to each individual compound, however 1 IU of retinol is equivalent to approximately 0.3 micrograms (300 nanograms).
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
 
|drugShortage=
==Nutrition==
}}
{| align="right" width="300" border="1" cellspacing="0" cellpadding="3" style="margin: 0 0 0 0.5em; background: #FFFFFF; border-collapse: collapse"
<!--Pill Image-->
|-
! bgcolor="#ffddaa" colspan="2" | Vitamin properties
|-
| bgcolor="#ffeedd" | [[Solubility]]
| Fat
|-
| bgcolor="#ffeedd" | [[Recommended Dietary Allowance|RDA]] (adult male)
| 900 [[microgram|µg]]/day
|-
| bgcolor="#ffeedd" | RDA (adult female)
| 700 [[microgram|µg]]/day
|-
| bgcolor="#ffeedd" | RDA upper limit (adult male)
| 3,000 [[microgram|µg]]/day
|-
| bgcolor="#ffeedd" | RDA upper limit (adult female)
| 3,000 [[microgram|µg]]/day
|-
! bgcolor="#ffeedd" colspan="2" | Deficiency symptoms
|-
| colspan="2" |
* [[Night blindness]]
* [[Keratomalacia]]
* Pale, dry skin
|-
! bgcolor="#ffeedd" colspan="2" | Excess symptoms
|-
| colspan="2" |
* Liver toxicity
* Dry skin
* Hair loss
* [[Teratogenesis|Teratological]] effects
* [[Osteoporosis]] (suspected, long-term)
|-
! bgcolor="#ffddaa" colspan="2" | Common sources
|-
| colspan="2" |
* [[Liver]]
* fortified [[Dairy products]]
* Darkly colored [[fruit]]s
* [[Leafy vegetable]]s
|-
|}
This vitamin plays an essential role in vision, particularly night vision, normal bone and tooth development, reproduction, and the health of skin and mucous membranes (the mucus-secreting layer that lines body regions such as the respiratory tract). Vitamin A also acts in the body as an antioxidant, a protective chemical that may reduce the risk of certain cancers.


There are two sources of dietary vitamin A. Active forms, which are immediately available to the body are obtained from animal products. These are known as retinoids and include retinal and retinol. Precursors, also known as provitamins, which must be converted to active forms by the body, are obtained from fruits and vegetables containing yellow, orange and dark green pigments, known as carotenoids, the most well-known being beta-carotene. For this reason, amounts of vitamin A are measured in Retinal Equivalents (RE). One RE is equivalent to 0.001 mg of retinal, or 0.006 mg of beta-carotene, or 3.3 International Units of vitamin A.


In the intestine, vitamin A is protected from being chemically changed by vitamin E. Vitamin A is fat-soluble and can be stored in the body. Most of the vitamin A you eat is stored in the liver. When required by a particular part of the body, the liver releases some vitamin A, which is carried by the blood and delivered to the target cells and tissues.


===Dietary intake===
<!--Label Display Image-->
The [[Dietary Reference Intake]] (DRI) Recommended Daily Amount (RDA) for Vitamin A for a 25-year old male is 900 micrograms/day, or 3000 IU.


The [[Food Standards Agency]] states that an average adult should not consume more than 1500 micrograms (5000 IU) per day, because this increases the chance of [[osteoporosis]].


During the absorption process in the [[intestine]]s, retinol is incorporated into [[chylomicron]]s as the ester form, and it is these particles that mediate transport to the [[liver]]. Liver cells ([[hepatocyte]]s) store vitamin A as the ester, and when retinol is needed in other tissues, it is de-esterifed and released into the blood as the alcohol. Retinol then attaches to a serum carrier, [[retinol binding protein]], for transport to target tissues. A binding protein inside cells,  [[cellular retinoic acid binding protein]], serves to store and move retinoic acid [[intracellular]]ly. Carotenoid [[bioavailability]] ranges between 1/5 to 1/10 of retinol's. Carotenoids are better absorbed when ingested as part of a fatty meal. Also, the carotenoids in vegetables, especially those with tough cell walls (e.g. carrots), are better absorbed when these cell walls are broken up by cooking or mincing.


===Deficiency===
:''see [[Vitamin A deficiency]] for details''
[[Image:Vitamin A deficiency.PNG|right|thumb|360px|Prevalence of vitamin A deficiency. Source: [[World Health Organization|WHO]]]]
Vitamin A deficiency is common in developing countries but rarely seen in developed countries. Approximately 250,000 to 500,000 malnourished children in the developing world go blind each year from a deficiency of vitamin A. [[Night blindness]] is one of the first signs of vitamin A deficiency. Vitamin A deficiency contributes to blindness by making the [[cornea]] very dry and damaging the [[retina]] and cornea.


===Retinoid overdose (toxicity)===<!-- This section is linked from [[Cod liver oil]] -->
:''see [[Hypervitaminosis A]] for details''
The [[Dietary Reference Intake|Tolerable Upper Intake Level]] (UL) for vitamin A, for a 25-year old male, is 3,000 micrograms/day, or about 10,000 IU.


Too much vitamin A in retinoid form can be harmful or fatal, resulting in what is known as hypervitaminosis A. The body converts the dimerized form, [[carotene]], into vitamin A as it is needed, therefore high levels of carotene are not toxic compared to the ester (animal) forms. The livers of certain animals, especially those adapted to polar environments, often contain amounts of vitamin A that would be toxic to humans. Thus, vitamin A toxicity is typically reported in Arctic explorers and people taking large doses of synthetic vitamin A. The first documented death due to vitamin A poisoning was [[Xavier Mertz]], a [[Switzerland|Swiss]] scientist who died in January 1913 on an [[Antarctica|Antarctic]] expedition that had lost its food supplies and fell to eating its sled dogs. Mertz consumed lethal amounts of vitamin A by eating the dogs' livers.<ref>[http://www.studentbmj.com/back_issues/0502/life/158.html An account of Mertz's illness], retrieved 20 June 2007.</ref>  
<!--Category-->


If eaten in one meal, 30 to 90 grams of [[polar bear]] liver is enough to kill a human being, or to make even sled dogs very ill. <ref>[http://prof_anil_aggrawal.tripod.com/poiso032.html A. Aggrawal, Death by Vitamin A]</ref>
[[Category:Drug]]
 
Excess vitamin A has also been suspected to be a contributor to [[osteoporosis]]. This seems to happen at much lower doses than those required to induce acute intoxication. Only preformed vitamin A can cause these problems, because the conversion of carotenoids into vitamin A is downregulated when physiological requirements are met. An excessive uptake of carotenoids can, however, cause [[carotenosis]].
 
The carotenoid [[beta carotene]] was interestingly associated with an increase in [[lung cancer]] when it was studied in a lung cancer prevention trial in male smokers. In non-smokers, the opposite effect has been noted.
 
Excess preformed vitamin A during early pregnancy has also been associated with a significant increase in birth defects.<ref>Challem, Jack, [http://www.thenutritionreporter.com/A-vitamins.html Caution Urged With Vitamin A in Pregnancy: But Beta-Carotene is Safe], ''The Nutrition Reporter Newsletter'', 1995, retrieved 20 June 2007.</ref> These defects may be severe, even life-threatening. Even twice the daily recommended amount can cause severe birth defects.<ref>Stone, Brad. [http://www.fda.gov/bbs/topics/ANSWERS/ANS00689.html Vitamin A and Birth Defects], 6 October 1995, retrieved 20 June 2007.</ref> The FDA currently recommends that pregnant women get their Vitamin A from foods containing beta carotene and that they should ensure that they consume no more than 5,000 IU of preformed Vitamin A (if any) per day. Although Vitamin A is necessary for fetal development, most women carry stores of Vitamin A in their fat cells, so oversupplementation should be strictly avoided.
 
A review of all randomized controlled trials in the scientific literature by the [[Cochrane Collaboration]] published in [[Journal of the American Medical Association|JAMA]] in 2007 found that vitamin A significantly ''increased'' mortality by 16% (Relative Risk 1.16, 95% confidence interval 1.10-1.24).<ref>Bjelakovic et al., [http://jama.ama-assn.org/cgi/content/abstract/297/8/842 Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: Systematic review and meta-analysis], ''JAMA'', 297:842; February 28, 2007.</ref>
 
===Sources===
All [[Vitamin_A#Sources|sources of vitamin A]] can provide retinol, but retinoids are found naturally in some foods of animal origin. Each of the following contains at least 0.15 mg of retinoids per 1.75-7 oz. (50-200 g):
* [[Cod Liver Oil]]
* [[Butter]]
* [[Liver]] (beef, pork, chicken, turkey, fish)
* [[Egg (food)|Eggs]]
 
===Synthetic Sources===
[[Chemical synthesis|Synthetic]] retinol is marketed under the following trade names: Acon, Afaxin, Agiolan, Alphalin, Anatola, Aoral, Apexol, Apostavit, Atav, Avibon, Avita, Avitol, Axerol, Dohyfral A, Epiteliol, Nio-A-Let, Prepalin, Testavol, Vaflol, Vi-Alpha, Vitpex, Vogan, and Vogan-Neu.
 
===Night vision===
Night blindness—the inability to see well in dim light—is associated with a deficiency of [[vitamin A]]. At first, the most light sensitive (containing more retinal) protein [[rhodopsin]] is influenced. Less pigmented by retinal [[iodopsin]]s (three forms/colors in humans), responsible for [[color vision]] and sensing relatively high light intensities (day vision), are less impaired at early stages of the [[vitamin A]] deficiency. All these protein-pigment complexes are located in the light-sensing cells in eye's [[retina]].
 
When stimulated by light, rhodopsin splits into a protein and a cofactor: opsin and all-''trans''-retinal (a form of vitamin A). The regeneration of active rhodopsin requires opsin and 11-''cis''-retinal. The regeneration of 11-''cis''-retinal occurs in vertebrates via a sequence of chemical transformations that constitute "the visual cycle" and which occurs primarily in the retinal pigmented epithelial cells.
 
Without adequate amounts of retinal, regeneration of rhodopsin is incomplete and night blindness occurs. Since carrots are a good source of beta-carotene, there is truth in the old belief that carrots help you see better in the dark.
 
==Closely related chemicals==
*[[Tretinoin]] (Tradename: Retin-A)
*[[Isotretinoin]] (Tradename: Accutane(US), Roaccutane)
*Retinyl palmitate ("vitamin A" or "pro-vitamin A")
 
==Genetically engineered vitamin A enriched rice==
Due to the high prevalence of vitamin A deficiency in [[developing country|developing countries]], there are efforts to produce [[genetically modified]] rice rich in beta carotene. The idea is that this would help poor people, who can not afford a varied diet containing sufficient natural sources of vitamin A, meet their dietary needs. The [[golden rice]] project is one such effort, and is already undergoing trials.
 
== References ==
<references/>
 
==External links==
* {{pauling|id=vitamins/vitaminA|title=Vitamin A|author=Jane Higdon}}
*[http://ods.od.nih.gov/factsheets/cc/vita.html NIH Office of Dietary Supplements - Vitamin A]
*[http://www.biochemj.org/bj/348/0481/bj3480481.htm Retinol binding protein]
*[http://www.merck.com/mrkshared/mmanual/section1/chapter3/3b.jsp Merck Manual of Diagnosis and Therapy: Vitamin A Deficiency]
*[http://www.who.int/nutrition/publications/vitamin_a_pub/en/index.html WHO publications on Vitamin A Deficiency]
*[http://news.bbc.co.uk/2/hi/health/6677631.stm BBC News article on Retinol's use as an anti-wrinkle cream]
 
 
{{Nasal preparations}}
{{Vitamin}}
{{Carotenoids}}
[[Category:Vitamins]]
[[Category:Vitamins]]
[[Category:Alcohols]]
[[Category:Alcohols]]
[[Category:Terpenes and terpenoids]]
[[Category:Retinoids]]
[[Category:Antioxidants]]
[[Category:Antioxidants]]
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[[ar:فيتامين أي]]
[[bs:Vitamin A]]
[[ca:Retinol]]
[[cs:Vitamín A]]
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[[fa:ویتامین آ]]
[[fr:Vitamine A]]
[[ko:바이타민 A]]
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[[id:Retinol]]
[[is:A-vítamín]]
[[it:Retinolo]]
[[he:ויטמין A]]
[[ku:Rêtînol]]
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Latest revision as of 17:04, 20 August 2015

Retinol
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Disclaimer

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Overview

Retinol is a vitamin analog that is FDA approved for the treatment of acne vulgaris. Common adverse reactions include hypopigmentation, hyperpigmentation, skin erythema.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

  • RETIN-A is indicated for topical application in the treatment of acne vulgaris. The safety and efficacy of the long-term use of this product in the treatment of other disorders have not been established.
  • RETIN-A Gel, Cream or Liquid should be applied once a day, before retiring, to the skin where acne lesions appear, using enough to cover the entire affected area lightly. Liquid: The liquid may be applied using a fingertip, gauze pad, or cotton swab. If gauze or cotton is employed, care should be taken not to oversaturate it to the extent that the liquid would run into areas where treatment is not intended. Gel: Excessive application results in “pilling” of the gel, which minimizes the likelihood of over application by the patient.
  • Application may cause a transitory feeling of warmth or slight stinging. In cases where it has been necessary to temporarily discontinue therapy or to reduce the frequency of application, therapy may be resumed or frequency of application increased when the patients become able to tolerate the treatment.
  • Alterations of vehicle, drug concentration, or dose frequency should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.
  • During the early weeks of therapy, an apparent exacerbation of inflammatory lesions may occur. This is due to the action of the medication on deep, previously unseen lesions and should not be considered a reason to discontinue therapy.
  • Therapeutic results should be noticed after two to three weeks but more than six weeks of therapy may be required before definite beneficial effects are seen.
  • Once the acne lesions have responded satisfactorily, it may be possible to maintain the improvement with less frequent applications, or other dosage forms.
  • Patients treated with RETIN-A (tretinoin) acne treatment may use cosmetics, but the area to be treated should be cleansed thoroughly before the medication is applied.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Retinol in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Retinol in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Retinol in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Retinol in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Retinol in pediatric patients.

Contraindications

  • Use of the product should be discontinued if hypersensitivity to any of the ingredients is noted.

Warnings

There is limited information regarding Retinol Warnings' in the drug label.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Retinol in the drug label.

Postmarketing Experience

  • The skin of certain sensitive individuals may become excessively red, edematous, blistered, or crusted. If these effects occur, the medication should either be discontinued until the integrity of the skin is restored, or the medication should be adjusted to a level the patient can tolerate. True contact allergy to topical tretinoin is rarely encountered.
  • Temporary hyper or hypopigmentation has been reported with repeated application of RETIN-A. Some individuals have been reported to have heightened susceptibility to sunlight while under treatment with RETIN-A. To date, all adverse effects of RETIN-A have been reversible upon discontinuance of therapy

Drug Interactions

There is limited information regarding Retinol Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

  • Oral tretinoin has been shown to be teratogenic in rats when given in doses 1000 times the topical human dose. Oral tretinoin has been shown to be fetotoxic in rats when given in doses 500 times the topical human dose.
  • Topical tretinoin has not been shown to be teratogenic in rats and rabbits when given in doses of 100 and 320 times the topical human dose, respectively (assuming a 50 kg adult applies 250 mg of 0.1% cream topically). However, at these topical doses, delayed ossification of a number of bones occurred in both species. These changes may be considered variants of normal development and are usually corrected after weaning. There are no adequate and well-controlled studies in pregnant women. Tretinoin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Retinol in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Retinol during labor and delivery.

Nursing Mothers

  • It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when RETIN-A is administered to a nursing woman.

Pediatric Use

There is no FDA guidance on the use of Retinol with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Retinol with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Retinol with respect to specific gender populations.

Race

There is no FDA guidance on the use of Retinol with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Retinol in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Retinol in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Retinol in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Retinol in patients who are immunocompromised.

Administration and Monitoring

Administration

Monitoring

  • Alterations of vehicle, drug concentration, or dose frequency should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.

IV Compatibility

There is limited information regarding IV Compatibility of Retinol in the drug label.

Overdosage

  • If medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur. Oral ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A

Pharmacology

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Template:Chembox header2 | Retinol
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
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UNII
Properties
C20H30O
Molar mass 286.46 g·mol−1
Template:Chembox header2 | Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Mechanism of Action

  • Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased microcomedo formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedone.

Structure

  • RETIN-A Gel, Cream and Liquid, containing tretinoin are used for the topical treatment of acne vulgaris. RETIN-A Gel contains tretinoin (retinoic acid, vitamin A acid) in either of two strengths, 0.025% or 0.01% by weight, in a gel vehicle of butylated hydroxytoluene, hydroxypropyl cellulose and alcohol (denatured with tert-butyl alcohol and brucine sulfate) 90% w/w. RETIN-A (tretinoin) Cream contains tretinoin in either of three strengths, 0.1%, 0.05%, or 0.025% by weight, in a hydrophilic cream vehicle of stearic acid, isopropyl myristate, polyoxyl 40 stearate, stearyl alcohol, xanthan gum, sorbic acid, butylated hydroxytoluene, and purified water. RETIN-A Liquid contains tretinoin 0.05% by weight, polyethylene glycol 400, butylated hydroxytoluene and alcohol (denatured with tert-butyl alcohol and brucine sulfate) 55%. Chemically, tretinoin is all-trans-retinoic acid and has the following structure:
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Retinol in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Retinol in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Retinol in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Retinol in the drug label.

How Supplied

This image is provided by the National Library of Medicine.

Storage

  • RETIN-A Liquid, 0.05%, and RETIN-A Gel, 0.025% and 0.01%: store below 86°F. RETIN-A Cream, 0.1%, 0.05%, and 0.025%: store below 80°F.

Images

Drug Images

{{#ask: Page Name::Retinol |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.

{{#ask: Label Page::Retinol |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Retinol in the drug label.

Precautions with Alcohol

  • Alcohol-Retinol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Retinol Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Retinol Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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