You are Now Free to Move About the Ganglia Acyclovir, Valacyclovir, Famciclovir, Cidofovir, Foscarnet

8.1 – “You are Now Free to move about the Ganglia”: Acyc Acyclovir, lovir, valacyclovir, famciclov famciclovir, ir, cidofovir, foscarnet • Oral purine nucleoside analogs used for HSV (Hermes for herpes) & VZV (Zeus) infections • Acyclovir, valacyclovir, famciclovir all treat HSV. Short course of 7-10 d Tx with primary oral, genital, HSV infection → ↓viral shedding, time for lesion healing, and ↓local pain. Does not affect recurrence rates. o Can offer in recurrence daily to take any of the medications daily. Valacyclovir preferred as it is dosed qid & has superior bioavailability (“valet parking for frequent flyers” & “Daily rate” signs; attendant popping pills over “↑available↑” sign) o Can also be used as HSV prophylaxis in immunocompromised patients (lady with cane) ▪ In pregnancy with active recurrent genital herpes, give suppressant acyclovir at 36w to reduce risk of C-section & active shedding (pregnant lady) ▪ Transplant patients (organs on ice) • Acyclovir (recycling bins) o G-purine nucleoside analog that gets Ⓟ via herpesvirus encoded thymidine kinas → acyclovir monophosphate; occurs selectively in virus-infected cells (guanosine nucleoside shaped Gucci luggage labeled with Ⓟ luggage tag by Hermes attendant). This is the rate-determining activation step (“Rate limit”) (also the point where bugs can develop resistance). Subsequent Ⓟ steps taken over by cellular kinases (blue-collar workers slapping on 2nd & 3rd). Triphosphate can compete with deoxy-guanosine triphosphate. When incorporated, halts viral DNA synthesis via DNA-dependent DNA polymerase (bags jamming DNA-shaped conveyor belt) o Absence of thymidine kinase confers resistance (absence of attendant at closed baggage check) o Effective against herpes zoster (shingles is reactivated VZV) o Only drug here that is available for IV use in US (ivy). ▪ Treatment of serious HSV & VZV infection, including HSV encephalitis (helmet wings), neonate HSV infection (baby). • Valacyclovir o Acyclovir prodrug with better oral bioavailability (oral eating; ↑available) o Effective against herpes zoster (Zeus sign). Superior activity and less frequent dosing. ▪ Hasten resolution of cutaneous lesions & acute neuritis. ▪ Unknown effect on post-herpetic neuralgia. ▪ Valacyclovir & famciclovir are most effective when administered within 3d of symptom onset (“Great Value: 3-Day family vacation”) • Famciclovir o Effective against herpes zoster (“3-Day family vacation”) • Cidofovir (Cid the security guard) o Does not require viral kinase Ⓟ so effective against acyclovir or ganciclovir resistant HSV, VZV, CMV (Cid the security officer has Ⓟ tags so can bypass the closed luggage counter). This is especially important in immunocompromised patients, as thymidine resistant strains of VZV are found almost exclusively in immunocompromised populations o Directly inhibits viral DNApol (security officer directly turning off conveyor belts). • Foscarnet (car with a net) o Does not require Ⓟ by viral kinase (cart bypassing closed checkpoint). Active against acyclovir or ganciclovir resistant HSV, VZV, CMV. o Directly inhibits viral DNApol; pyrophosphate analog that selectively inhibits the pyrophosphate binding site on viral DNApols (security officer directly turning off conveyor belts). • Adverse effects o IV acyclovir can cause interstitial nephritis or crystalline nephropathy (sharp crystalline objects causing tubular obstruction in kidney shaped can). Uncommon with slower infusion rate & sufficient hydration (tossing water bottles) o All can cause CNS effects (delirium confusion, vertigo, hallucinations). Especially with high dose a/o IV administration (shaky kid setting off alarm in detector)