Isotretinoin Chemische Eigenschaften,Einsatz,Produktion Methoden
R-S?tze Betriebsanweisung:
R61:Kann das Kind im Mutterleib sch?digen.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
R20/21/22:Gesundheitssch?dlich beim Einatmen,Verschlucken und Berührung mit der Haut.
S-S?tze Betriebsanweisung:
S53:Exposition vermeiden - vor Gebrauch besondere Anweisungen einholen.
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn m?glich, dieses Etikett vorzeigen).
S37/39:Bei der Arbeit geeignete Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
Beschreibung
Isotretinoin is the 9-cis isomer of retinoic acid, a close relative of retinol, or vitamin A. It was originally developed to treat cystic acne, and today this is still its primary use despite several more modern applications of the drug, including a treatment for pancreatic and brain cancers. First shown to be an effective treatment for acne in 1982, its development stemmed from advances in knowledge of the effects of vitamin A to reduce or eliminate sebum production. Since that time, however, several instances of deleterious effects became well known, most notably birth defects arising from the use of isotretinoin.
Chemische Eigenschaften
Yellow or orange crystalline powder or crystal, insoluble in water, slightly soluble in ethanol, very slightly soluble in ether, soluble in chloroform.
History
After a 1979 article reported Isotretinoin's effectiveness against cystic and conglobate acne, Roche submitted a New Drug Application to the Food and Drug Administration (FDA).
Despite prior correlation of isotretinoin with birth defects, Isotretinoin (brand name Accutane) quickly became the dominant acne treatment prescribed by dermatologists and general practitioners alike. In 1983, the FDA made the unprecedented decision to warn blood banks against accepting the blood of donors taking isotretinoin and instruct women to begin taking contraceptives one month before use. In 1985, the FDA further required a boxed warning to be added, but the problem grew with an estimated 1000 birth defects attributed to the drug by early 1988.
In 2001, the FDA announced the System to Manage Accutane Related Teratogenicity (SMART), which required Roche to train doctors for a sticker-based system of verifying that female patients took pregnancy tests before using Accutane.
In February 2002, Roche's patents for isotretinoin expired, allowing generic drugs to enter the market. By June 2009, Roche discontinued the Accutane brand amid falling market share and rising costs from personal injury lawsuits. However, Roche's overseas affiliates continue to sell isotretinoin as Roaccutane.
Verwenden
isotretinoin is a retinoid derivative with improved bioavailability and percutaneous absorption for acne treatment products. Presently being studied in conjuction with the treatment of photoaged skin.
synthetische
Preparation of isotretinoin in a single step from β-ionone and ethyl chloride are first reacted together after which the product is further reacted with triphenylphosphine to obtain Triphenyl salt. The Triphenyl salt is further reacted with cyclopentenone derivative to produce isotretinoin and its 8Z isomer. separate out the 8Z isomer and convert it to isotretinoin through isomerization with the help of nitric acid.
Definition
ChEBI: Isotretinoin is a retinoic acid that is all-trans-retinoic acid in which the double bond which is alpha,beta- to the carboxy group is isomerised to Z configuration. A synthetic retinoid, it is used for the treatment of severe cases of acne and other skin diseases. It has a role as a keratolytic drug, an antineoplastic agent and a teratogenic agent. It is a conjugate acid of a 13-cis-retinoate.
Indications
Isotretinoin (Accutane) alters keratinization in the
acroinfundibulum of sebaceous glands and shrinks
them, thereby reducing sebum excretion and comedogenesis.
These features underlie its usefulness in acne
vulgaris, since sebum secretion is a hallmark of acneprone
skin. Furthermore, the drug has antiinflammatory
activity.
Weltgesundheitsorganisation (WHO)
Isotretinoin, a retinol derivative, was introduced in 1982 exclusively for the treatment of severe acne. Its use in pregnant women has
resulted in major fetal abnormalities. The manufacturer's information emphasizes
that the drug is teratogenic and must not be given to women who are pregnant,
and that contraceptive measures must be maintained for at least four weeks after
discontinuation of treatment. In some countries, blood banks are advised not to
accept as donors persons who have taken isotretinoin within the previous four
weeks. See also under retinol (vitamin A).
Allgemeine Beschreibung
Yellow-orange to orange crystalline powder; orange-brown chunky solid.
Air & Water Reaktionen
Insoluble in water.
Reaktivit?t anzeigen
An organic acid and unsaturated aliphatic hydrocarbon. Carboxylic acids donate hydrogen ions if a base is present to accept them. They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat. Neutralization between an acid and a base produces water plus a salt. Insoluble carboxylic acids react with solutions of cyanides to cause the release of gaseous hydrogen cyanide. Flammable and/or toxic gases and heat are generated by the reaction of carboxylic acids with diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides. Carboxylic acids, especially in aqueous solution, also react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat. Their reaction with carbonates and bicarbonates generates a harmless gas (carbon dioxide) but still heat. Like other organic compounds, carboxylic acids can be oxidized by strong oxidizing agents and reduced by strong reducing agents. These reactions generate heat. A wide variety of products is possible. Like other acids, carboxylic acids may initiate polymerization reactions; like other acids, they often catalyze (increase the rate of) chemical reactions.
Brandgefahr
Flash point data for Isotretinoin are not available; however, Isotretinoin is probably combustible.
Mechanism of action
Isotretinoin binds to and activates nuclear retinoic acid receptors (RARs); activated RARs serve as transcription factors that promote cell differentiation and apoptosis. This agent also exhibits immunomodulatory and anti-inflammatory responses and inhibits ornithine decarboxylase, thereby decreasing polyamine synthesis and keratinization. Isotretinoin is rapidly absorbed orally, with peak blood concentrations 3 hours after ingestion. It is not stored in tissue, and the elimination half-life is 10 to 20 hours, either after a single dose or during chronic therapy.
Clinical Use
Isotretinoin is most useful for the treatment of severe
recalcitrant nodular acne vulgaris. It may also be helpful in other disorders of keratinization, but it is
not useful for psoriasis. High doses of isotretinoin
(2mg/kg/day) are effective as cancer chemoprevention
agents to reduce the frequency of cutaneous malignancies
in patients at increased risk, such as those with xeroderma
pigmentosum, an inherited disorder in which
DNA repair is deficient, or in immunosuppressed patients.
Nebenwirkungen
Isotretinoin is teratogenic to humans and should not be administered to pregnant women or women contemplating pregnancy. Concomitant use of isotretinoin with drugs of the tetracycline class increases the incidence of Pseudotumor cerebri. There have been recent reports of an increased risk of depression, suicide, and suicide attempts in individuals taking isotretinoin, but the causality has not been absolutely proved.
Isotretinoin, like many retinoids, can lead to increase in serum aminotransferase levels, but, unlike acitretin and etretinate, isotretinoin has not been clearly implicated in cases of clinically apparent acute liver injury with jaundice.
Sicherheitsprofil
Poison by
intraperitoneal route. Moderately toxic by
ingestion. A human teratogen by ingestion
with fetal developmental abnormalities of
the skin and appendages and other postnatal
effects. Human reproductive effects. Human
systemic effects: decreased immune
response, darrhea, hypermouhty, irritative
dermatitis, sweating. Human mutation data
reported. An experimental teratogen. Other
experimental reproductive effects. When
heated to decomposition it emits acrid
smoke and irritating fumes.
Isotretinoin Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
