1. Acyclovir
    • Monophosphorylated by HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination
    • Use: HSV, VZV, EBV. No effect on latent forms. Valacyclovir a prodrug has better oral bioavailability
    • Famciclovir for herpes zoster
    • Toxicity: minor
    • Resistance: lack of thymidine kinase
  2. Ganciclovir
    • thymidine kinase in HSV and 5'-monophosphate (phosphotransferase) formed by a CMV viral kinase. Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase. chain temination
    • Use: CMV, HSV, CMV, Valganciclovir is prodrug
    • Toxicity: Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir because can be phosphorlated by human kinase.
    • Resistance: mutated CMV DNA polymerase or lack of viral kinase
  3. Foscarnet
    • Viral DNA and RNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme. Doesn't require activation by viral kinase
    • Use: CMV retinitis when ganciclovir fails, acyclovir resistant HSV
    • Toxicity: nephrotoxicity w/ acute tubular necrosis, electrolyte imbalance w/ hypocalcemia; avoid given w/ pentamidine IV.
    • Resistance: mutated DNA polymerase
  4. Nucleotide reverse transcriptase inhibitors (NRTI)
    • Competitively inhibit RNA dependent- DNA polymerase --> terminate the DNA chain (lack a 3'-OH group). Must be phosphorylated by thymidine kinase to be active.
    • Zidovudine (ZDV formerly AZT) used for general prophylaxis and during pregnancy to reduce risk of fetal transmission
    • AZT: Bone marrow suppression (can be reversed w/ G-CSF and erythropoietin), peripheral neuropathy, lactice acidosis (associated w/ mitochondrial DNA toxicity by inhibiting DNA polymerase), rash, megaloblastic anemia (ZDV)
    • Didanosine DDI: pancreatitis, peripheral neuropathy, hyperuricemia, liver dysfunction
    • Zalcitabine DDC: peripheral neuropathy, pancreatitis, neutropenia, rash
    • Stavudine D4T: peripheral neuropathy
    • Lamivudine 3TC: least toxic of the NRTIs, but some GI effects and neutropenia. Active in hepatitis B
    • Emtricitabine FTC
    • Abacavir ABC
    • Tenofovir TDF
  5. Non-nucleotide reserve transcriptase inhibitors (NNRTIs)
    • bind to reverse transcriptase at site different from NRTIs. Don't require phosphorylation to be active or compete w/ nucleotides.
    • No myelosuppression
    • NeVIRapine: dec vertical transmission, induces P450, rash, inc LFTs
    • EfaVIRenz: insomnia, nightmairs
    • DelaVIRdine
  6. Protease Inhibitors
    Lopinavir, atazanavir, darunavir, saquinavir, ritonavir
    • assembly of virions depends on HIV-1 protease (pol gene) which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses
    • Ritonavir can boost other drug concentrations by inhibiting P450
    • Hyperglycemia, lipodystrophy
  7. Enfuvirtide
    binds gp41 and inhibits fusion of HIV-1 to CD4+ cells
  8. Maraviroc
    blocks CCR5 protein on T-cel surface to prevent viral entry
  9. Raltegravir
    • inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
    • hypercholesterolemia
  10. Amantadine
    • blocks attachment, penetration, and uncoating (M2 protein) of influenza A virus. also causes the release of dopamine from intact nerve terminals (used to treat Parkinson's).
    • Toxicity: ataxia, dizziness, slurred speech (causes problems w/ the cerebella), livedo reticularis
    • Resistance: mutated M2 protein. 90% of all influenza A strains are resistant to amantadine, so not used
  11. Zanamivir, oseltamivir
    inhibit neuraminidases of influenza A and B. dec likelihood that the virus will penetrate uninfected cells.
  12. Ribavirin
    • monophosphorylated form inhibits IMP dehydrogenase
    • Triphosphate inhibits viral RNA polymerase and end-capping of viral RNA
    • Use: RSV, chronic hepatitis C
    • Toxicity: hemolytic anemia. Sevre teraogen avoid pregnancy for > 6 months thereafter
  13. interferons
    • glycoproteins synthesized by virus-infected cells block replication of both RNA and DNA viruses
    • Use: IFN-alpha- chronic hepatitis B and C, Kaposi's sarcoma; IFN-beta-MS; IFN-gamma-NADPH oxidase deficiency
    • Toxicity: neutropenia
Card Set
antiviral drugs