Amantidine, rimantidine - mechanism
Blocks viral penetration (uncoating - "a man to dine" takes off his coat - via M2 protein); maybe by buffering endosome pH. Also causes DA release from nerve terminals
Amantidine, rimantidine - use
PPX, Tx for influenza A. 90% influenza A strains resistant to amatadine (not used) - via mutated M protein.
Parkinson's disease, Rubella too
Amantidine, rimantidine - toxicity
Ataxia, dizziness, slurred speech. Rimantadine has fewer CNS side effects; doesn't cross BB
Zanamivir, oseltamivir - mechanism
Inhibit influenza neuraminidase; decreasing release of progeny virus
Zanamivir, oseltamivir - use
Influenza A & B
Ribavirin - mechanism
Competitive inhibitor of IMP dehydrogenase (inhibits guanine nucleotide synthesis)
Ribavirin - use
Chronic hepatitis C
Ribavirin - toxicity
Severe teratogen (IMP dehydrogenase inhibitor!)
Acyclovir - mechanism
Chain terminator; preferentially inhibits viral DNApol. Mono-P-lated by HSV/VZV thymidine kinase; guanosine analog; triphosphate formed by cellular enzymes.
Acyclovir - use
HSV, VZV, EBV
HSV-induced mucocutaneous / genital lesions; also encephalitis; PPx in immunocompromised. No effect on latent HSV/VZV. Resistance via lack of thymidine kinase
Acyclovir - toxicity
Generally well toleraetd
Famciclovir - use
Related to acyclovir; used for herpes zoster
Ganciclovir - mechanism
Chain terminator; preferentially inhibits viral DNApol
5'-MP formed by CMV viral kinase or HSV/VZV thymidine kinase; guanosine analog; triphosphate formed by cellular kinases
Ganciclovir - use
CMV (esp. immunocompromised pts). Resistance via mutated CMV DNApol; lack of viral kinase
Ganciclovir - toxicity
More toxic to host enzymes than acyclovir. Leukopenia, neutropenia, thrombocytopenia, renal toxicity
Foscarnet - mechanism
Viral DNApol inhibitor (PPi analog; binds to pyrophosphate-binding site). No viral kinase activation needed.
Foscarnet - use
CMV retinitis in immunocompromised pts when ganciclovir fails; HSV if acyclovir-resistant.
Resistance via mutated DNApol
Foscarnet - toxicity
Saquinavir, ritonavir, indinavir, nelfinavir, amprenavir - mechanism
Protease inhibitors - inhibit maturation of HIV by blocking protease in progeny virions.
Saquinavir, ritonavir, indinavir, nelfinavir, amprenavir - use
HIV triple therapy.
Ritonavir - blocks CYP450 metabolism ("boosting")
Saquinavir, ritonavir, indinavir, nelfinavir, amprenavir - toxicity
GI intolerance (nausea, diarrhea)
Zidovudine (ZDV / AZT), didanosine (ddI), zalcitabine (ddC), lamivudine (3TC), abacavir (ABC) - mechanism
Nucleoside reverse transcriptase inhibitors (NRTIs). Preferentially inhibit HIV reverse transcriptase, preventing incorporation of DNA copy of viral genome into host DNA
Nevirapine, Efavirenz, Delavirdine - mechanism
on-nucleoside reverse transcriptase inhibitors (NNRTIs). Preferentially inhibit HIV reverse transcriptase, preventing incorporation of DNA copy of viral genome into host DNA. Bind away from nucleoside binding site.
NRTIs / NNRTIs - common toxicities
Bone marrow suppression (neutropenia, anemia), peripheral neuropathy. GM-CSF and EPO can be used to reduce bone marrow suppression.
NRTIs - toxicity
Megaloblastic anemia (ZDV = AZT)
NNRTIs - toxicity
Enfuvirtide - mechanism
Fusion inhibitor. Binds HIV gp41 subunit; inhibits conformational change needed for fusion with CD4+ cells; blocks entry / replication
Enfuvirtide - use
HIV pts with persistent viral replication despite HAART; used in combo
Enfuvirtide - toxicity
Hypersensitivity reactions; reactions at subQ injection site, increased risk of bacterial pneumonia.
Interferons - mechanism
Glycoproteins from human leukocytes; block various stages of viral RNA/DNA synthesis. Induce ribonuclease (degrades viral mRNA)
Interferon alpha - use
Chronic hepatitis B/C; Kaposi's sarcoma
Interferon beta - use
NADPH oxidase deficiency
Interferons - toxicity