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Herpes/CMV

Non-retroviral agents

QuestionAnswer
Herpes Simplex 1 & 2 1 - oral 2 - genital
Varicella-Zoster chicken pox, shingles
Alpha herpes virus HSV 1 & 2, VZV
Beta herpes virus CMV, HHV 6 & 7 (HH-human herpes virus)
Gamma herpes virus EBV (Epstein-Barr), HHV 8
CMV will cause CMV retinitis, encephalitis in HIV, colitis, pneumonitis, CNS infection lead to organ disease; occur most in advanced immunosuppressed pts
Anti-Herpes and anti-CMV agents inhibit what to stop infection? DNA polymerase (copy viral DNA)
Anti-Herpes Agents acyclovir,valacyclovir, famciclovir, docosanol (abreva), penciclovir, trifluridine
Acyclovir, penciclovir; ganciclovir (treat CMV) (anti herpes agent) requires activation by 3 phosphorylation; 1st-viral thymidine kinase;competitive inhibition of viral DNA polymerase and inhibition of viral DNA synthesis=chain termination; 2.5-3hrs; excretion-kidneys; drink water to prevent nephrotoxicity;10x potent
mutation of DNA polymerase (enzyme no longer inhibited by drug) and viral thymidine (drug is no longer activated) resistance to anti-herpes agents
Valacyclovir (anti herpes agent) ester prodrug of acyclovir (greater absorption, 3-5x blood levels)
Famciclovir (anti herpes agent) active against all herpes except CMV, needs to activated, NVD/HA, good absorption
Docosanol (abreva) (anti herpes agent) 22 carbon alcohol, inhibits HSV fusion (entry) w/cell membrane; topical
Penciclovir (anti herpes agent) topical, active metabolite of famciclovir, excreted urine (kidneys)
Trifluridine (anti herpes agent) fluorinated pyrimidine nucleoside, need no activation
Anti-CMV Agents ganciclovir, valganciclovir, foscarnet, cidofovir; inhibit CMV (viral) DNA polymerase
acyclovir,valacyclovir, famciclovir, docosanol (abreva), penciclovir, trifluridine Anti-Herpes Agents
ganciclovir, valganciclovir, foscarnet, cidofovir Anti-CMV Agents
Ganciclovir (anti-CMV agent) need activation (phosphyloration) by CMV specific kinase, excreted renal, poor PO absorption, IV/intraocular implant (CMV retinitis); 4 hrs, cleared by dialysis, MYELOSUPPRESSION, neutropenia, NVD, rash, HA, altered liver enzymes, peripheral neuropathy
Valganciclovir (anti-CMV agent) ester prodrug of ganciclovir, take w/food, excreted renal, well absorbed, metabolized in liver and intestinal wall to be converted to ganciclovir, lost via dialysis
Foscarnet (anti-CMV agent) inhibits viral DNA/RNA polymerase and HIV RT WITHOUT phosphorylation (no activation)against wide-range of HSV 1 and 2, CMV, VZV, EBV; excreted renal, toxic, IV only, 3-7 hrs, poor PO absorption, NEPHROTOXICITY
Foscarnet interactions/S&S (anti-CMV agent) aminoglycosides:nephrotoxicity-NVD, anemia,altered ca+/phosphate levels,high urine concentrations, genital ulcerations, high liver enzymes impenem(beta lactam - carbapenems group)=seizures CNS toxicity: HA, hallucinations, seizures (impenem interaction)
Cidofovir (anti-CMV agent) potent inhibitor of viral DNA polymerase, broad spectrum(HSV,CMV),phosphorylated independent of viral kinases(not specific-bad);excreted renal,infused w/probenecid to prevent tubular secretion of cidofovir and nephrotoxicity; neutropenia, uveitis (uvea)
prehydrate w/NS to prevent dose-dependent renal tubule toxicity cidofovir (anti-CMV agent)
Cidofovir (anti-CMV agent) avoid with other nephrotoxicity meds: aminoglycosides, foscarnet, NSAIDS
need no activation (phosphyloration) by viral kinase foscarnet (HSV agent), cidofovir (CMV agent, trifluridine (HSV agent)
inhibition of viral DNA polymerase acyclovir,vidarabine,foscarnet,ganiciclovir
esters added to drug for better absorption than in the tissues
Viral DNA polymerase enzyme that makes copies of viral DNA (replication)
Created by: cburrows
 

 



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