Acyclovir and Valacyclovir
antiviral agents used to treat HSV, VZV, and CMV (cytomegalovirus)
How do acyclovir and valacyclovir work?
The drugs are converted by thymidine kinase (an enzyme unique to infected cells) into a charged molecule. This charge prevents the drugs from passing out of the cell, resulting in accumulation inside the cell. At a certain concentration the drug is integrated into the replicating viral DNA which results in blocking of DNA synthesis.
Administration considerations for acyclovir and valacyclovir.
- - Valacyclovir is only available orally.
- - Oral absorption of acyclovir is slow and often incomplete (15-30%)
- - Patients must be well hydrated to decrease renal crystallization and prevent decrease inrenal function
An antiviral used to treat HSV and VZV.
How does famciclovir work?
Famciclovir is given orally and converted to active penciclovir once absorbed. Famciclovir is a prodrug.
Antiviral used to treat HSV.
Administration considerations for penciclovir.
- Not absorbed orally (to use penciclovir perenterally it must be administered orally as famciclovir).
- Only given topically.
- Inhibits DNA polymerase.
Treatment for Herpes Simplex Encephalitis.
Treatment/prophylaxis for HSV (herpes labialis).
- Treatment: Penciclovir or Acyclovir cream
- Prophylaxis: Pencivlovir cream (for sun-induced episodes)
Treatment for genetal herpes.
- Acyclovir, Valaciclovir, or Famciclovir PO (all are equally effective).
- None prevent frequency of recurrences.
- All decrease but do not prevent transmission of the virus.
- Topical acyclovir is NOT recommended.
- Prophylaxis (using the smallest effective dose of the same drugs daily) is preferred over episodic treatement.
Treatment for chickenpox caused by VZV.
Treatment for shingles caused by VSV.
- Start w/i 48hrs of onset for best results.
- Acyclovir, Valacyclovir, or Famciclovir (in immunocompetent pt).
- Acyclovir (in immunocompromised pt).
Postherpetic neuralgia - what is it and how is it treated?
- Occurs after shingles - intense pain.
- Early, aggressive treatment may decrease intensity and duration of pain.
- Tx: lidocain patch, caosaicin cream, gabapentin PO, or opiods PO
What are the more toxic antivirals, used for severe cases?
How do Ganciclovir, Valgancyclovir, and Foscarnet work?
They bind to cytomegolovirus (CMV) DNA polymerase and prevent viral replication.
What are Ganciclovir, Valgancyclovir, and Foscarnet used to treat?
- CMV (cytomegalovirus) infections in immunocompromised pts.
- CMV retinitis in immunocompromised pts.
- Acyclovir-resistant HSV or VSV
Administration considerations for Ganciclovir, Valgancyclovir, and Foscarnet.
- - Handle as a hazardous drug.
- - CMV retinitis: prophylactic therapy with ganciclovir or foscarnet is continued indefinitely.
- - Gancyclovir is available as an ocular insert for tx of CMV retinitis
Toxicities of Ganciclovir, Valgancyclovir, and Foscarnet.
- Gan/Valgancyclovir: neutropenia, thrombocytopenia
- Foscarnet: nephrotoxicity (make sure to hydrate pt well)
Drug interactions with Ganciclovir.
Zidovudine/azathioprine/mycophenolate mofetil (celcept) - increases hetatologic toxicity (consider foscarnet instead of ganciclovir)
antiviral used for CMV retinitis
How does cidofovir work?
Same a ganciclovir - binds to CMV DNA polymerase and inhibits viral replication. Conversions to active form is independent of viral enzymes.
Administration considerations for cidofovir.
Hydrate pt well and give probenicid prior to each dose of cidofir to prevent renal toxicity.
What are the neuraminidase inhibitors?
- zanamivir (inhaled) and oseltamivir (capsule)
- used to treat influenza A and B
How do zanamivir and oseltamivir work?
As neuraminidase inhibitors, they prevent neuraminidase from breaking the bond between viral particles and the cell membrane, thus preventing the release and spread of new viral particles.
Toxicities of zanamivir and oseltamivir (neuraminidase inhibitors)
- Zanamivir (inhaled) can cause bronchospasms.
- Nausea, vomitting.
Antiviral used to treat RSV and Hep B
Toxicities of Ribavirin
- Teratogen: women of childbearing age should not be exposed to the drug.
- Hemolytic anemia
- Handle as a hazardous drug.