Acyclovir (Zovirax), an antiviral drug, a synthetic analogue of acyclic purine nucleotide that possesses a highly selective action on herpes viruses. Inside virus infected cells under the action of the viral thymidine kinase is a series of sequential reactions of transformation of acyclovir into mono-, di – and triphosphate of acyclovir. Acyclovir triphosphate is incorporated into the viral DNA chain, and blocking its synthesis by competitive inhibition of viral DNA polymerase.
The drug is generally well tolerated. Gastrointestinal: in single cases — abdominal pain, nausea, vomiting, diarrhea. In the blood: a transient slight increase in the activity of liver enzymes, rarely — a slight increase in levels of urea and creatine, hyperbilirubinemia, leukopenia, eritropeniya. CNS: rarely — headache, weakness; in some cases, tremor, dizziness, fatigue, drowsiness, hallucinations. Allergic reactions: skin rash. Other: rarely — alopecia, fever.
Almost all of the world’s population is infected with herpes infection, but only every fourth or fifth disease is shown. Herpes infection can occur it is atypical, and can get very “bright” and even a danger to life (with brain damage).
The herpes virus is not only unpleasant but also dangerous: it interferes in personal life and in sports. For the prevention of diseases caused by herpes infection, we need not only a healthy lifestyle, good nutrition, high levels of personal hygiene, but also tempering, and sports.
Acyclovir, or 9-[(2-hydroxyethoxy)methyl]guanine, is an acyclic analogue of guanosine. side radical which is devoid of hydroxyl group in the S’-position. Acyclovir is produced in the form of capsules, ointments and powder for preparation of solution for I/V administration. Valacyclovir is the L-kalinovy ester of acyclovir. Acyclovir only for herpes viruses. In vitro it is most active against herpes simplex virus type 1 (at concentrations of 0.02 to 0.9 ág/ml); its activity against herpes simplex virus type 2 is almost 2 times less (0,03—2,2 µg/ml) and against the virus varicella-zoster, and Epstein—Barr — about 10 times smaller (0.8 to 4 µg/ml). The least active against cytomegalovirus (in concentrations greater than 20 µg/ml) and human herpesvirus type 6 (Wagstaff et al., 1994). The proliferation of the herpes viruses uninfected mammalian cells generally do not suppress even at high concentrations (> 50 µg/ml) of acyclovir.
Selectivity of acyclovir is determined by its interaction with two viral proteins. Capture cells acyclovir and its transformation into a monophosphate take part in the viral thymidine kinase. The affinity of acyclovir for this enzyme in 200 times more than timidinkinaze mammalian cells. Under the action of cellular enzymes from kalaekilohana cream acyclovircream is formed, the concentration of the latter in infected cells in 40-100 times higher than in free from the virus, so acyclovircream competes with endogenous deoxy-GTP. Myco-phenolic acid reduces the concentration of intracellular deoxy-GTP, thereby increasing the antiviral activity of acyclovir and drugs. Acyclovircream low inhibits viral and, to a much lesser extent, cellular DNA polymerase. In addition, it integrates itself into viral DNA and — in the absence of the hydroxyl group at the S’-position ribnogo ring stops its replication. The DNA molecule, which include acyclovir, binds to DNA polymerase and irreversibly inactivates it.
Resistance of HSV to acyclovir can lead to reduced activity of viral thymidine kinase, its substrate specificity (e.g., maintaining activity against the enzyme, it stops fosfauriliruet acyclovir), and changes in viral DNA polymerase. Changes in viral enzymes occur due to point mutations, i.e. insertions and deletions of nucleotides in the corresponding genes. Sustainable can be wild strains and viruses isolated from patients after treatment with antiviral drugs. Herpes simplex virus resistance to acyclovir most frequently occurs because of reducing the activity of viral thymidine kinase, at least — because of a change in substrate specificity of this enzyme. In more rare cases, mutations in the gene for the DNA polymerase. The strain is considered stable, if acyclovir does not act on it in vitro at concentrations above 2-3 mg/ml. in patients with a weakened immune system to cure the infection caused by this strain is not possible.