Antiviral

• 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

• 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

• 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

• 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

• 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

• 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

binds gp41 and inhibits fusion of HIV-1 to CD4+ cells

blocks CCR5 protein on T-cel surface to prevent viral entry

• inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
• hypercholesterolemia

• 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

inhibit neuraminidases of influenza A and B. dec likelihood that the virus will penetrate uninfected cells.

• 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

• 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