Acyclovir (Oral)

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Aciclovir is an antiviral medication. It works by stopping the production of the herpes virus. This reduces the length and severity of an outbreak of herpes.

Acyclovir can also be taken long term to reduce the number of herpes outbreaks in people who experience this condition often.

Acyclovir does not get rid of the virus from the body.

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[edit] STRUCTURE

Acyclovir.jpg

[edit] MECHANISM OF ACTION

Acyclovir is an acyclic guanine nucleoside analogue. It's an analogue of guanosine which lacks the 3’–OH involved in the phosphodiester bond between nucleotides. Therefore, it inhibits viral DNA replication.

Acyclovir is a narrow spectrum agent, used against the herpes virus only.

Acyclovir is phosphorylated by viral thymidine kinase to acyclovir monophosphate, the aciclovir affinity to viral thymidine kinase is much greater than for human thymidine kinase and therefore the phosphorylation reaction occurs more rapidly in cells infected with herpes virus than in normal cells.

Subsequently Acyclovir monophosphate is further converted to diphosphate and triphosphate by cellular enzymes.

Acyclovir-triphosphate enters in competition with deoxyguanosine triphosphate, and it's incorporation into viral DNA prevents DNA chain elongation (chain terminator) due to the lack of 3’–OH involved in the phosphodiester bond between nucleotides. The terminated DNA template containing acyclovir binds the enzyme and leads to irreversible inactivation of the DNA polymerase.

Herpes viruses encoding the thymidine kinase (herpes simplex and varicella-zoster) are much more sensitive to Acyclovir than those that do not encode it (CMV and Epstein-Barr virus).


Pharmacokinetics

  • Low bioavailability. It has a 10 – 30% oral absorption and so a very high oral dose is needed to treat chicken pox
  • It is eliminated by renal filtration and tubular secretion

To compensate for its low bioavailability, a prodrug, Valacyclovir, was produced. Valacyclovir has a higher oral bioavailability about 70% and is hydrolysed in the liver to produce acyclovir.

[edit] INDICATIONS

  • Adult Patients:
    • Herpes simplex (cold sores around the mouth)
    • Herpes Zoster (shingles)
    • Genital Herpes
    • Chickenpox (Varicella Zoster Virus VZV);
    • Acyclovir can be used for pneumonia or encephalitis due to VZV. It can also be used for ophthalmic zoster.


In immunoresponsive patients, most benefits are observed in the first treatment with acyclovir. In later treatment of recurrent infection, there is generally a lower response to acyclovir.

[edit] DOSAGE

  • Adults:
    • Herpes simplex: 200-400mg 5 times a day for 5 days
    • Genital Herpes: 200mg 5 times a day for 7 to 10 days
    • Herpes Zoster (shingles): 800 mg 5 times a day for 7 to 10 days.
    • Chickenpox (Adults and Children over 40 kg): 800 mg 4 times daily for 5 days


  • Children (2 years of age and older):
    • Chickenpox: 20 mg/kg per dose orally 4 times daily for 5 days

Begin use without regard to meals, as soon as possible following the development of symptoms

[edit] CONTRAINDICATIONS

[edit] WARNINGS AND PRECAUTIONS

  • Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid. Adequate hydration should be maintained for all patients (Take Valaciclovir with plenty of fluid)

[edit] INTERACTIONS

The pharmacological interactions which increase toxicity include:

  • Acyclovir + Zidovudine (NRTI) = higher neurotoxicity
  • Acyclovir + Cyclosporin (immunosuppressant) = higher nephrotoxicity
  • Acyclovir + Methotrexate (anti-folate) = reduced renal clearance

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category B (US).Acyclovir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • During lactation, Acyclovir should be administered with caution and only when indicated.

[edit] MECHANISM OF RESISTANCE

  • Mutation in the gene for thymidine kinase.
  • Reduced production of thymidine kinase, which would cause a decreased activation of acyclovir. Generally, the absence or reduced production of thymidine kinase is the most frequent mechanism of resistance by HSV and VZV.
  • Altered production of viral DNA polymerase is less common but is sometimes seen in VZV.

Resistant Herpes Simplex viruses are especially found in AIDS patients who receive chronic treatment with acyclovir. Since these patient are treated with different types of drugs, many resistant viral strains are found in them especially when these patients are treated to suppress the recurrence of genital herpes infection.

[edit] SIDE EFFECTS

Most common side effects may include headache, vomiting, nausea, and abdominal pain.

  • Nephrotoxicity and neurotoxicity from oral administration and IV infusion: Acyclovir is eliminated by renal clearance, therefore, elderly patients and patients with impaired kidney function are more susceptible to nephrotoxicity/neurotoxicity and therefore the need for dose reduction must be considered. Nephrotoxicity can also result from accumulation of the drug.

[edit] RELATED LINKS

What is Acyclovir
Useful natural treatments to treat herpes

[edit] BIBLIOGRAPHY

[edit] REFERENCES