Questions and Answers
Which nucleoside analog is a prodrug of acyclovir?
What is the mechanism of action of acyclovir and penciclovir in treating VZV infections?
Why is foscarnet sometimes preferred in nucleoside-resistant cases of VZV infections?
What potential risk is associated with the use of brivudin in the United States?
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What is an advantage of using famciclovir over penciclovir?
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What is the primary mechanism of action of amenamevir?
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In patients with herpes zoster, which antiviral medication showed comparable efficacy to valacyclovir?
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Why are famciclovir, valacyclovir, or acyclovir preferred for oral therapy of VZV infections?
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What is a notable characteristic of acyclovir-resistant VZV mutants?
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Which antiviral agent has been shown to be effective against acyclovir-resistant strains?
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Study Notes
Treatment of Varicella and Herpes Zoster
- Varicella-zoster virus (VZV) infections, including chickenpox and shingles, are treated primarily with antiviral medications.
- Effective antivirals include nucleoside analogs: acyclovir, famciclovir, valacyclovir, brivudin, and the pyrophosphate analog foscarnet.
Mechanism of Action
- Acyclovir and penciclovir are guanosine analogs; they are preferentially activated by viral thymidine kinase, minimizing toxicity to uninfected cells.
- These drugs are phosphorylated to monophosphates, which convert to triphosphates that inhibit viral DNA synthesis by blocking viral DNA polymerase.
Sensitivity and Dosage
- VZV exhibits approximately tenfold lower sensitivity to acyclovir and penciclovir compared to Herpes Simplex Virus (HSV).
- Prodrugs like valacyclovir (converted to acyclovir) and famciclovir (converted to penciclovir) demonstrate better absorption and higher blood levels, allowing for less frequent dosing.
Specific Antivirals
- Brivudin: A thymidine analog with strong activity against VZV but not approved in the U.S. due to potential interactions with other drugs (e.g., 5-fluorouracil).
- Foscarnet: Second-line drug acting as a pyrophosphate analog; inhibits replication of all herpesviruses without requiring activation by thymidine kinase, effective against nucleoside-resistant VZV but more toxic compared to nucleoside analogs.
- Cidofovir: Directly inhibits viral DNA polymerase but is considered less favorable due to high toxicity, classifying it as a third-line treatment.
- Amenamevir: A potent helicase-primase inhibitor effective against acyclovir-resistant VZV and HSV; comparable effectiveness to valacyclovir in herpes zoster treatment.
Treatment Considerations
- Topical antiviral therapy is ineffective for varicella and only has limited use in herpes zoster; systemic therapy (oral or parenteral) is the standard treatment.
- Famciclovir or valacyclovir are preferred over acyclovir for oral therapy due to superior pharmacokinetics and VZV's lower sensitivity.
- Acyclovir-resistant VZV may emerge in severely immunocompromised patients, such as those with advanced AIDS. These strains are typically resistant to other nucleoside analogs but may respond to foscarnet and are sensitive to amenamevir.
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Description
Explore the detailed treatment options for varicella and herpes zoster as covered in Chapter 191. This quiz focuses on the efficacy of nucleoside analogs like acyclovir and others in treating VZV infections. Test your understanding of these antiviral medications and their mechanisms of action.
