Questions and Answers
What is the main mechanism of action of Foscarnet?
Inhibits viral DNA polymerase by directly binding to it
Which of the following is a key advantage of Foscarnet over acyclovir and ganciclovir?
Activity against drug-resistant strains
What is the primary indication for Famciclovir use?
Prevention of CMV infections in organ transplant recipients
How does the bioavailability of Famciclovir compare to Penciclovir?
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Which of the following is a common adverse effect associated with Foscarnet?
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What is the primary mechanism of action of Penciclovir?
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Which of the following is a key advantage of Valganciclovir over Ganciclovir?
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Which of the following viruses is Aciclovir primarily used to treat?
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What is the primary advantage of Famciclovir over Aciclovir for the treatment of recurrent herpes labialis?
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Which of the following is a common adverse effect associated with Penciclovir?
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Study Notes
Antivirals for Herpes Viruses
- Valaciclovir: prodrug of aciclovir, improved bioavailability (54-70%), converted to aciclovir by cellular enzymes
- Indications: herpes zoster virus (shingles), acute genital HSV, prevention and treatment of recurrent herpes genitalis, mucocutaneous HSV
- A/E: oral (nausea, vomiting, diarrhea, headache), I.V (nephrotoxic, reversible, phlebitis at injection site), topical (burning, stinging)
Ganciclovir and Valganciclovir
- Ganciclovir: aciclovir analogue, inhibits viral DNA replication, 100x more active against cytomegalovirus (CMV) than aciclovir
- Valganciclovir: prodrug of ganciclovir, poor oral bioavailability, converted to ganciclovir by intestinal and hepatic esterases
- Activity against HSV and VZV: equal to aciclovir
Penciclovir
- Similar to acyclovir, but only topical
- MOA: penciclovir triphosphate inhibits herpes DNA synthesis by acting as a false substrate for viral DNA polymerase
- Indication: treatment of recurrent orolabial herpes simplex
Herpes Simplex Virus (HSV)
- HSV1: oral herpes (cold sores)
- HSV2: genital herpes
- Herpes Zoster Virus (HZV): shingles
- Varicella Zoster Virus (VZV): chicken pox
Aciclovir
- Guanosine derivative (nucleoside analogue)
- Prodrug: activated in infected cells
- MOA: aciclovir triphosphate (active form) incorporated into viral DNA, irreversibly inhibits viral DNA polymerase
- Indications: treatment of HSV (I & II), varicella zoster virus, prophylaxis of recurrent episodes (>6/year) of herpes genitalis
- PK: T1/2 = 2-3hrs, 10-30% orally bioavailable, renally eliminated
Famciclovir
- Diacetyl 6-deoxy analogue of penciclovir
- Oral indications: CMV retinitis prophylaxis and treatment in immunocompromised patients, prevention of CMV infections in organ transplant patients
- A/E: myelosuppression, neutropenia, thrombocytopenia
- Rapidly absorbed, 77% bioavailability, metabolized into penciclovir, excreted renally as penciclovir and its 6-deoxy precursor
Foscarnet
- Non-nucleoside DNA polymerase inhibitor
- MOA: direct inhibition of DNA polymerase, not incorporated into the growing viral DNA
- Active against herpes, varicella, and CMV, including those resistant to acyclovir and ganciclovir
- A/E: nephrotoxicity
Antivirals for Hepatitis
- Interferons (IFNs): immunomodulator/biological agents, produced in lab by rDNA technology
- Indications: treatment of chronic Hepatitis B and C
- Other antiviral drugs for hepatitis: Ribavirin, Entecavir, Tenofovir, Emtricitabine, Lamivudine
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