Aciclovir Chemische Eigenschaften,Einsatz,Produktion Methoden
R-Sätze Betriebsanweisung:
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S22:Staub nicht einatmen.
S24/25:Berührung mit den Augen und der Haut vermeiden.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
Beschreibung
As it is evident from the chemical structure, acyclovir looks like a nucleoside analog of
guanosine in side chain of which, instead of the traditional cyclic sugar residue a 2-hydroxyethoxymethyl acyclic side chain is present. Acyclovir possesses antiviral activity with
respect to types 1 and 2 of herpes simplex, shingles virus, Epstein–Barr virus, and
cytomegalovirus.
Chemische Eigenschaften
white to light yellow crystal powder
Verwenden
Acyclovir (Zovirax) is a synthetic purine analog derived from guanine. It exerts its effects on the herpes simplex virus (HSV) and varicella-zoster virus by interfering with DNA synthesis through phosphorylation by viral thymidine kinase and subsequent inhibition of viral DNA polymerase, thereby inhibiting viral replication. It is effective against HSV-1 and 2, varicella-zoster virus, Epstein-Barr virus, herpesvirus simiae, and cytomegalovirus. Acyclovir may be administered intravenously, orally, or topically.
Definition
ChEBI: An oxopurine that is guanine substituted by a (2-hydroxyethoxy)methyl substituent at position 9.
Indications
Acyclovir (Zovirax) is a synthetic purine analog derived from guanine. It exerts
its effects on the herpes simplex virus (HSV) and varicella-zoster virus by interfering
with DNA synthesis through phosphorylation by viral thymidine kinase and
subsequent inhibition of viral DNA polymerase, thereby inhibiting viral replication.
It is effective against HSV-1 and 2, varicella-zoster virus, Epstein-Barr
virus, herpesvirus simiae, and cytomegalovirus. Acyclovir may be administered
intravenously, orally, or topically.
Acyclovir (400 mg PO b.i.d. or 200 mg PO five times a day) or other antiviral
antibiotics can suppress herpes-associated EM. It is of no value once the EM has
started. Not all episodes of a herpes simplex recurrence are associated with EM,
but in recurrent cases, a 6-month trial of suppressive therapy can be helpful.
Antimicrobial activity
Activity is restricted to viruses of the herpes group. Herpes simplex
virus (HSV) types 1 and 2, simian herpes virus B and varicella
zoster viruses (VZV) are susceptible to concentrations
readily attainable in human plasma. The 50% inhibitory concentration
(ID50) is 0.1 μmol for HSV-1 and HSV-2 and 3 μmol for
VZV, concentrations much below those toxic to cells. Valaciclovir
is metabolized to aciclovir, and has the same antiviral profile.
Thymidine-kinase-negative HSV mutants and cytomegalovirus
(CMV) do not code for thymidine kinase and are generally
resistant. Although Epstein–Barr virus (EBV) may have reduced
thymidine kinase activity, its DNA polymerase is susceptible
to aciclovir triphosphate and shows intermediate susceptibility.
Human herpes viruses 6 and 7 are less susceptible than EBV.
Acquired resistance
Mutations in HSV that involve deficient thymidine kinase
or an altered substrate are most common; alterations in the
DNA polymerase gene also result in resistance. Resistant
mutants may be found in wild virus populations; mutants
lacking thymidine kinase activity may be readily induced
by passage of HSV in the presence of the drug. Resistant
strains have mostly been reported in immunocompromised
patients, are generally thymidine-kinase negative, and have
decreased virulence. Resistant mutants that retain thymidine
kinase activity appear to retain virulence. Emergence of
resistant HSV strains is less frequent in immunocompetent
patients, occurring in about 2% of those receiving prolonged
treatment.
Allgemeine Beschreibung
Acyclovir, 9-[2-(hydroxyethoxy)methyl]-9H-guanine (Zovirax),is the most effective of a series of acyclic nucleosidesthat possess antiviral activity. In contrast with true nucleosidesthat have a ribose or a deoxyribose sugar attached to apurine or a pyrimidine base, the group attached to the basein acyclovir is similar to an open chain sugar, albeit lackingin hydroxyl groups. The clinically useful antiviral spectrumof acyclovir is limited to herpesviruses. It is most active (invitro) against HSV type 1, about two times less against HSVtype 2, and 10 times less potent against varicella–zostervirus (VZV).
The ultimate effect of acyclovir is the inhibition of viralDNA synthesis. Transport into the cell and monophosphorylationare accomplished by a thymidine kinase that is encodedby the virus itself.The affinity of acyclovir for the viralthymidine kinase is about 200 times that of the correspondingmammalian enzyme.
use: oral and parenteral. Oral acyclovir is used in the initialtreatment of genital herpes and to control mild recurrentepisodes. It has been approved for short-term treatment ofshingles and chickenpox caused by VZV. Intravenous administrationis indicated for initial and recurrent infectionsin immunocompromised patients and for the prevention andtreatment of severe episodes. The drug is absorbed slowlyand incompletely from the GI tract, and its oral bioavailabilityis only 15% to 30%. Nevertheless, acyclovir is distributedto virtually all body compartments.
Pharmazeutische Anwendungen
A synthetic acyclic purine nucleoside analog of the natural
nucleoside 2′ deoxyguanosine, formulated for oral and
topical use, and as the sodium salt for intravenous infusion.
Valaciclovir (the l-valyl ester) is a prodrug formulation supplied
as the hydrochloride for oral use.
Biologische Aktivität
Antiviral agent, active against herpes simplex viruses HSV-1 and HSV-2 (EC 50 values are 0.85 and 0.86 μ M respectively). Interferes with viral DNA polymerization through competitive inhibition with guanosine triphosphate. Induces apoptosis in cells transfected with HSV-TK (suicidal gene therapy).
Clinical Use
Aciclovir
Herpes simplex keratitis
Chickenpox and herpes zoster
Herpes simplex encephalitis and neonatal herpes
Prophylaxis of HSV infections in the severely immunocompromised
Valaciclovir
Herpes zoster and genital HSV infections
Aciclovir Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
