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Acyclovir
Mechanism:
| • | a synthetic acyclic purine nucleoside analogue |
| • | phosphorylation of drug depends on HSV-specific thymidine kinase |
| • | acyclovir triphosphate inhibits viral DNA polymerase (therefore effective against replicating, but not latent, virus) |
acyclovir, famciclovir, valacyclovir:
| • | all 3 agents, as well as ganciclovir, interfere with viral DNA synthesis and require viral thymidine kinase for their activity |
| • | Foscarnet (phophonoformic acid) directly inhibits viral DNA polymerase and therefore is often effective in resistant HSV (because most likely cause for resistance is thymidine kinase mutants) |
Valacyclovir
| • | mnemonic – “val” acyclovir (a more bioa- “val”- able form of acyclovir) |
| • | converted to acyclovir after absorption but bioavailability is 3 to 5X greater |
Famcyclovir
| • | = oral form of pencyclovir |
| • | like acyclovir: viral encoded thymidine kinase à monophosphate |
| • | cellular enzymes à triphosphate |
| • | inhibits DNA polymerase (therefore viral replication) |
| • | advantage over acyclovir = increased half-life (20 hours vs. 1 hour in HSV-2 infected cells) |
valacyclovir = pro-drug of acyclovir
famciclovir = pro-drug of pencyclovir
Ted Rosen pearl – antiviral prophylaxis during entire third trimester of any pregnant woman with history of genital HSV
| • | dose = valacyclovir 1000mg/day; acyclovir 400mg/TID (these are higher than normal suppressive doses) |
resistant HSV: Foscarnet; still resistant: cidofovir
| • | Ted Rosen pearl - try viroptic (ophthalmic solution) QID to lesion |
| • | 1/3 to ¼ of acyclovir resistant cases will respond |
| • | (because viroptic does not need thymidine kinase activation) |
| • | avoids the dangerous and difficult IV meds (listed above) |
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