Aciclovir

The to aciclovir (DCI), marketed under the name of Zovirax® or Activir® , is one of principal the Médicament S antiviral. Its discovery was felt like the beginning of a new era in the therapy Antiviral E, because of its very great specificity and of its weak Cytotoxicité. However, to aciclovir it a sphere of activity very restricted, only effective has against some Virus like the HSV-1 and 2, and VZV, with an effectiveness limited against the Virus of Epstein-Barr (Epstein-Barr virus EBV) active, and it hardly acts against human form of the Cytomegalovirus (MVC). It acts approximately 10 times more against the HSV that against the VZV. It does not remove the virus of the Herpès, and is not very effective against the genital herpes at the woman. To aciclovir from the other similar nucleosidic is different because it comprises only one structure partial of Nucléoside, cyclic sugar being replaced by an open chain.

Mode of action

To aciclovir is converted into form monophosphate, aciclo-GMP, by the Thymidine viral Kinase, which is much more effective (3000 times) in phosphorylation that the thymidine cellular kinase. Then, the form monophosphate is phosphorylée in form activates triphosphate, aciclo-GTP, by cellular Kinase S. The aciclo- GTP is a very powerful inhibiter of DNA viral polymerase; it has 100 times roughly more affinity with the viral polymerase than the cellular polymerase. The form monophosphate to aciclovir it also acts while being incorporated in viral DNA lasting its replication, blocking the polymerization of this last, the viral Enzyme S not being able to cleave the aciclo-GMP proteinic chain of the DNA. The aciclo-GTP is very quickly metabolized in the cell, probably by cellular Phosphatase S.

Pharmacokinetic

To aciclovir is not very water soluble, and is only partially absorbed at the time of the catch by oral way (20%). At the time of the catch by oral way, the peak of concentration plasma tick is reached into 1 to 2 a.m. So of strong amounts are necessary, the administration must be made by intravenous way. To aciclovir profits from high a distribution, only 30% is fixed at proteins in plasma sanguin.
The Demi-vie of the product is approximately 3:00.
To aciclovir can also be managed locally (Pommade) for the processing of cutaneous herpetic infections or the Muqueuse S, like the genital herpes or the labial herpes. (cold sore)
The prophylactic administration is possible, in particular at the patients under Immunosuppresseur S or Radiothérapie or for the patients suffering from frequent pushes of labial or genital herpes.

Metabolism - Elimination

Elimination to aciclovir it is made via the renal system, partly by glomerular filtration, and partly by tubular secretion.
Renal problems were reported at the time of the fast administration of strong amounts per intravenous way, this because of crystallization to aciclovir it in will néphrons.

Side effects - Counter-indications

Since to aciclovir it can be built-in cellular DNA, it is a Mutagène of Chromosome, so its regulation must be avoided in the expectant mother. However, it shown Teratogenic effect forever or Carcinogenic.
The threshold of toxicity (LD₅₀) to aciclovir it at the time of the administration by oral way exceeds the 1mg/kg, because of the weak absorption by the gastro-intestinal tract. Isolated cases were reported, where extremely high amounts (until 80mg/kg) were accidentally managed by intravenous way, without causing secondaires.
effects The most current undesirable effects are a local irritation or a feeling of puncture or burn on the level of the enforcement zone of the pomade, and Céphalée S at the time of the catch by way orale.
Resistance to aciclovir it evolves/moves rather quickly, although this does not obstruct its clinical use. The resistant forms are generally viruses having undergone a change of their thymidine kinase or their DNA polymerase.

Indications

labial Herpes (and disease prevention)
genital Herpes (and disease prevention)
herpetic Keratitis
Herpes zoster (Shingles)
Chicken pox

References

Harvey Stewart C. in Remington' S Pharmaceutical Sciences 18th edition: (ED. Gennard, Alfonso R.) Mack Publishing Company, 1990. ISBN 0912734043.
Huovinen P., Valtonen V. in Kliininen Farmakologia (ED. Neuvonen and. Al). Kandidaattikustannus OY, 1994. ISBN 9519851179.
Périgaud C., Gosselin G., Imbach J. - L.: Nucleoside analogues ace chemotherapeutic agents: review has. Nucleosides and nucleotides 1992; 11 (2-4)
20. Row H.P., Flagstone M.M., Ritter J.M.: Pharmacology, 3^rd edition. Pearson Professional Ltd, 1995. 2003 (5th) edition ISBN 0443071454; 2001 (4th) edition ISBN 0443065748; 1990 edition ISBN 0443034079.

Random links: