Tretinoin
Encyclopedia
Tretinoin is the acid form of vitamin A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...

 and is also known as all-trans retinoic acid or ATRA. It is a drug commonly used to treat acne vulgaris
Acne vulgaris
Acne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea , comedones , papules , pustules , Nodules and possibly scarring...

 and keratosis pilaris
Keratosis pilaris
Keratosis pilaris is a common, autosomal dominant, genetic follicular condition that is manifested by the appearance of rough bumps on the skin...

. It is available as a cream or gel (brand names Aberela, Airol, Renova, Atralin, Retin-A, Avita, Refissa, or Stieva-A). It is also used to treat acute promyelocytic leukemia
Acute promyelocytic leukemia
Acute promyelocytic leukemia is a subtype of acute myelogenous leukemia , a cancer of the blood and bone marrow. It is also known as acute progranulocytic leukemia; APL; AML with t, PML-RARA and variants; FAB subtype M3 and M3 variant.In APL, there is an abnormal accumulation of immature...

 (APL), and is sold for this indication by Roche under the brand name Vesanoid. It is also available as a generic.

Dermatology

Tretinoin is most commonly used as a form of acne treatment. It was the first retinoid
Retinoid
The retinoids are a class of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth....

 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 also a component of many commercial products that are advertised as being able to slow skin aging or remove wrinkles. Topical
Topical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...

 tretinoin is also used to treat
Therapy
This is a list of types of therapy .* Adventure therapy* Animal-assisted therapy* Aquatic therapy* Aromatherapy* Art and dementia* Art therapy* Authentic Movement* Behavioral therapy* Bibliotherapy* Buteyko Method* Chemotherapy...

 and reduce the appearance of stretch marks
Stretch marks
Stretch marks or striae , as they are called in dermatology, are a form of scarring on the skin with an off-color hue. They are caused by tearing of the dermis, and over time can diminish but not disappear completely....

 by increasing collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...

 production in the dermis
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...

.

Leukemia

In addition, tretinoin (marketed as Vesanoid) is also used to treat at least one form of cancer (acute promyelocytic leukemia
Acute promyelocytic leukemia
Acute promyelocytic leukemia is a subtype of acute myelogenous leukemia , a cancer of the blood and bone marrow. It is also known as acute progranulocytic leukemia; APL; AML with t, PML-RARA and variants; FAB subtype M3 and M3 variant.In APL, there is an abnormal accumulation of immature...

 (APL), also called acute myeloid leukemia
Acute myeloid leukemia
Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...

 subtype M3), usually together with other drugs, by causing the immature blood cells 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 3 months at about 8-10 10 mg capsules per day.

Clinical pharmacology

Its success in treating acute promyelocytic leukemia was a major breakthrough in the treatment of this type of leukemia.
It works in APL because the majority of cases involve a chromosomal translocation of chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

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
Myeloid
The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...

 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
Promyelocyte
A promyelocyte is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte.-External links: - "18. Bone Marrow and Hemopoiesis: bone marrow smear, promyelocyte and erythroblasts " "Bone marrow" "Bone marrow"* - "Bone marrow smear"...

s to differentiate to normal mature blood cells thus decreasing promyelocytes.

In dermatological use

When used, dryness or increased sensitivity of the affected skin may occur. More sensitive of 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
Sunscreen
Sunblock is a lotion, spray, gel or other topical product that absorbs or reflects some of the sun's ultraviolet radiation on the skin exposed to sunlight and thus helps protect against sunburn...

, 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 mark for several days. Tweezing
Plucking (hair removal)
Plucking or tweezing can mean the process of removing human hair, animal hair or a bird's feathers by mechanically pulling the item from the owner's body.In humans, this is done for personal grooming purposes, usually with tweezers...

 or threading (epilation)
Threading (epilation)
Threading is an ancient method of hair removal originating in the Eastern world. In more recent times it has gained popularity in Western countries.-Technique:...

 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 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
Retinoic acid syndrome
Retinoic acid syndrome is a potentially life threatening complication observed in patients with acute promyelocytic leukemia and first thought to be specifically associated with all-trans retinoic acid treatment...

 in patients with acute promyelocytic leukemia. This is associated with the development of dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...

, fever, weight gain, peripheral edema and is treated with dexamethasone
Dexamethasone
Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...

. The etiology of retinoic acid syndrome has been attributed to capillary leak syndrome
Capillary leak syndrome
Capillary leak syndrome is a rare medical conditioncharacterized by self-reversing episodes during which the endothelial cells which line the capillaries are thought to separate for a few days, allowing for a leakage of fluid from the circulatory system to the interstitial space, resulting in a...

 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. 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
Retinol
Retinol is one of the animal forms of vitamin A. It is a diterpenoid and an alcohol. It is convertible to other forms of vitamin A, and the retinyl ester derivative of the alcohol serves as the storage form of the vitamin in animals....

 signaling, which plays a role in patterning the developing embryo. However the risks of topical tretinoin to the fetus seems to be limited.

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.
Studies suggested that 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 that further research is needed to reach conclusions on this treatment.

See also

  • Baldness treatments
    Baldness treatments
    Baldness treatment is a US $1 billion per year industry. In males past their early 20s, the incidence of balding is roughly equivalent to chronological age. Thus, by age 50, roughly half of men experience male pattern baldness . Beginning in the 1980s, drug therapy has increasingly become a...

  • Hypervitaminosis A syndrome
  • Talarozole
    Talarozole
    Talarozole is an investigational drug for the treatment of acne, psoriasis and other keratinization disorders....

    , an experimental drug potentiating the effects of tretinoin

Manufacture

External links

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