Vidarabin Chemische Eigenschaften,Einsatz,Produktion Methoden
R-Sätze Betriebsanweisung:
R63:Kann das Kind im Mutterleib möglicherweise schädigen.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S36/37:Bei der Arbeit geeignete Schutzhandschuhe und Schutzkleidung tragen.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
Beschreibung
Vidarabine (adenine arabinoside) is the stereoisomer of adenosine. This analog of a purine
nucleoside exhibits selective activity against the herpes virus. The ribose residue is replaced
with an arabinose residue. Like acyclovir, it turns into mono-, di-, and triphosphate in cells
infected by a virus, thus inhibiting DNA polymerase, and correspondingly preventing DNA
synthesis of the virus approximately 20–40 times more than in “host” cells. It is easily metabolized to a less active, yet nonetheless antiviral compound—arabinosylhypoxanthine. It has
been successfully used for herpetic encephalitis, and for complicated shingles. It is used in
the form of eye drops for herpetic keratoconjuctivitis. A synonym of this drug is Vira-A.
Chemische Eigenschaften
Crystalline
Verwenden
Vidarabine, is an antiviral drug which is active against herpes simplex and varicella zoster viruses.
Indications
Vidarabine (adenine arabinoside, Vira-A) is an adenine
nucleoside analogue containing arabinose in place of ribose.
It is obtained from cultures of Streptomyces antibioticus
and has activity against HSV-1, HSV-2, VZV,
CMV, HBV, poxviruses, hepadnaviruses, rhabdoviruses,
and certain RNA tumor viruses.
Allgemeine Beschreibung
Chemically, vidarabine (Vira-A), is 9--D-arabinofuranosyladenine.The drug is the 2'epimer of natural adenosine.Introduced in 1960 as a candidate anticancer agent, vidarabinewas found to have broad-spectrum activity against DNAviruses.The drug is active against herpesviruses,poxviruses, rhabdoviruses, hepadnavirus, and some RNAtumor viruses. Vidarabine was marketed in the United Statesin 1977 as an alternative to idoxuridine for the treatment ofHSV keratitis and HSV encephalitis. Although the agent wasinitially prepared chemically, it is now obtained by fermentationwith strains of Streptomyces antibioticus.
The antiviral action of vidarabine is completely confinedto DNA viruses. Vidarabine inhibits viral DNA synthesis.Enzymes within the cell phosphorylate vidarabine to thetriphosphate, which competes with deoxyadenosine triphosphatefor viral DNA polymerase. Vidarabine triphosphate isalso incorporated into cellular and viral DNA, where it actsas a chain terminator. The triphosphate form of vidarabinealso inhibits a set of enzymes that are involved in methylationof uridine to thymidine: ribonucleoside reductase, RNApolyadenylase, and S-adenosylhomocysteine hydrolase.
At one time in the United States, intravenous vidarabinewas approved for use against HSV encephalitis, neonatalherpes, and herpes or varicella zoster in immunocompromisedpatients. Acyclovir has supplanted vidarabine as thedrug of choice in these cases.
Air & Water Reaktionen
Insoluble in water.
Reaktivität anzeigen
Vidarabine is an aminoalcohol. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.
Brandgefahr
Flash point data for Vidarabine are not available; however Vidarabine is probably combustible.
Mechanism of action
Vidarabine’s specific mechanism of action is not
fully understood. Cellular enzymes convert this drug to
a triphosphate that inhibits DNA polymerase activity.
Vidarabine triphosphate competes with deoxyadenosine
triphosphate (dATP) for access to DNA polymerase
and also acts as a chain terminator. Although
vidarabine is incorporated into host DNA to some extent,
viral DNA polymerase is much more susceptible to
inhibition by vidarabine. Vidarabine also inhibits ribonucleoside
reductase and other enzymes. Resistance
occurs as a result of DNA polymerase mutation.
Pharmakokinetik
Vidarabine is deaminated rapidly by adenosine deaminase, which is present in serum and red blood cells.
The enzyme converts vidarabine to its principal metabolite, arabinosyl hypoxanthine (ara-HX), which has
weak antiviral activity. The half-life of vidarabine is approximately 1 hour, whereas
ara-HX has a half-life of 3.5 hours. The drug is detected mostly in the kidney, liver, and spleen, because
50% of it is recovered in the urine as ara-HX. Levels of vidarabine in CSF fluid are 50% of those in the
plasma.
Clinical Use
The principal use of vidarabine is in the treatment of
HSV keratoconjunctivitis. It is also used to treat superficial
keratitis in patients unresponsive or hypersensitive
to topical idoxuridine.
Nebenwirkungen
The most commonly observed side effects associated
with vidarabine are lacrimation, burning, irritation,
pain, and photophobia. Vidarabine has oncogenic and
mutagenic potential; however, the risk of systemic effects
is low because of its limited absorption. It should
not be used in conjunction with ophthalmic corticosteroids,
since these drugs increase the spread of HSV
infection and may produce side effects such as increased
intraocular pressure, glaucoma, and cataracts.
Sicherheitsprofil
Poison by ingestion and
intravenous routes. Moderately toxic by
intraperitoneal route. An experimental
teratogen. Other experimental reproductive
effects. Human systemic effects by
intravenous route: central nervous system,
blood, and other effects. A skin and eye
irritant. Human mutation data reported.
When heated to decomposition it emits
toxic fumes of NOx.
Vidarabin Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
