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48 Cards in this Set
- Front
- Back
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What is the mechanism of amantadine?
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Blocks viral penetration/uncoating by interfering with M2 protein - a viral membrane matrix protein - a channel required for fusion of viral membrane with cell membrane that ultimately forms the endosome. also causes release of DA from intact nerve terminals.
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What is the clinical use for Amantidine?
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Prophylaxis and treatment for influenza A and rubella; Parkinson's disease
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What are the toxicities of Amantadine?
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Ataxia, dizziness, slurred speech
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What is the mechanism of resistance for Amantadine? How resistant is influenza A?
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Mutated M2 protein. 90% of influenza A strains resistant so not used
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How is Ramntadine different from Amantadine?
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Ramantidine has fewer CNS side effects - does not cross the blood-brain barrier
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What is the mechanism of zanamivir and oseltamivir?
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Inhibit influenza neuraminidase, decreasing the release of progeny virus
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What viruses are zanamivir and oseltamivir used for?
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Influenza A and B
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What antiviral inhibit influenza neuraminidase?
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Zanamivir and oseltamivir
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What is the mechanism of action for Ribavirin?
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Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase
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What viruses does Ribavirin act against?
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RSv, chronic hepatitis C (when used in combo with INF-alpha-2b)
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What are the toxicities of Ribavirin?
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Hemolytic anemia. Severe teratogen
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How does acyclovir work?
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Guanosine analog. Monophosphorylated by HSV/VZV thymidine kinase. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination.
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What viruses are used for acyclovir?
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HSV, VZV, EBV, Used for HSV induced mucocutaneous and genital lesions as well as for encephalitis. Prophylaxis in immunocompromised patients.
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What antiviral is used for herpes zoster?
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Famciclovir
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True or falwse. Acyclovir has no effect on latent forms of HSV and VZV.
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TRUE
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What is a mechanism of resistance to acyclovir?
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Lack of thymidine kinase
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What antiviralsare used for HSV, VZV, EBV and is a guanonsine analog?
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Acyclovir, ganciclovir
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What are the toxicities of acyclovir?
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Generally well tolerated
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What is the mechanism of ganciclovir?
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Guanosine analog. 5'monophosphate formed by a CMV viral kinase or HSV/VZV thymidine kinase. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase
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What is the typical clinical use of ganciclovir?
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CMV, esp. in immunocompromised
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What is the mechanism of resistance to gancicloovir?
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Mutated CMV DNA polymerase or lack of viral kinase
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What is the mechanism of foscarnet?
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Viral DNA polymerase inhibitor that binds to the pyrophosphate binding site of the enzyme.
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Foscarnet is different from ganciclovir and acyclovir. . how?
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Does not require activation by viral kinase
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What is the clinical use for Foscarnet?
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CMV retinitis in immunocompromised patients when ganciclovir fails; acyclovir resistant HSV.
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What is the toxicity of Foscarnet
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Nephrotoxicity
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What is the mechanism of resistance to Foscarnet
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Mutated DNA polymerase
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What are the three classes of HIV therapy?
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Protease inhibitors, Reverse transcriptase inhibitors, Fusion inhibitors
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What is the mechanism of indinavir, and saquinavir and what class of drugs are these?
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Inhbit maturation of new virus by blocking protease in progeny virions. Protease inhibitors
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What are the toxicities of amprenavir and nelfinavir and this class ofdrugs?
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GI intolerance (nausea, diarrhea), hyperglycemia, lipodystrophy
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What toxicity of indinavir is different from the other proteases?
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TCP
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How do nucleoside RT inhibitors work? What are some main ones?
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Analogs of native ribosides that all lack a 3'hydroxyl group. Once in the cells they become triphosphoryated and incorporated into viral DNA. Because 3'oh is missing, 3'4 to 5' phosphodiester bond between incoming nucleoside triphosphate and growing DNA chain not formed and DNA chain enlongation by viral RT is inhbited. ZIDOVUDINE (ZDV, formerly AZT), DIDANOSINE (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), abacavir
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What class of drugs are Zidovudine, Didanosine, Zalcitabine, Stavudine, Lamivudine?
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Nucleoside reverse transcriptase inhibitors
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How do non-nucleoside RTs work?
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Highly selective, noncompetitive inhibitors of RT. Bind to site adjacent to active site, induce a conformational change that results in enzyme inhibition. NEVIRAPINE, EFAVIRENZ, DELAVIRDINE (Never Ever Deliver nucleosides)
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What are the toxicities of the reverse transcriptases?
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Bone marrow suppression (neutropenia, anemia), peripheral neuropathy, lactic acidosis (nucleoside RTs), rash (non-0nucleoside RTs), megaloblastic anemia (ZDV)
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What is the clinical use for reverse transcriptase inhibitors?
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Highly active antiretroviral therapy (HAART): Combo therapy with protease inhibitors and RT inhibitors. Used when patients have low CD4 counts (<500) or high viral load. ZDV used for general prophylaxis and during pregnancy to reduce risk of fetal transmission
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Which antiviral for HIV is used to reduce the risk of fetal transmission?
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ZDV - Zidovudine
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What is the name of a fusion inhibitor?
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Enfuviritide
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What is the mechanism of enfuviritide?
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Binds viral gp41 subunit, inhibits conformational change required for fusion with CD4 cells. BLOCK ENTRY AND SUBSEQUENT replciation
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What are the toxicities of enfuvirtide?
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Hypersensitivity rxns, rxns at subcutaneous injection site, increased risk of bacterial pneumonia
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What is the clinical use of enfuvirtide?
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Patients with persistent viral replication in spite of antiretroviral therapy
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What drug for HIV Binds viral gp41 subunit, inhibits conformational change required for fusion with CD4 cells. BLOCK ENTRY AND SUBSEQUENT replciation
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Enfuvirtide
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What are interferons?
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Glycoproteins from human leukocytes that block various stages of viral RNA and DNA synthesis. Induce ribonuclease that degrades viral mRNA
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What INF can be used for chronic hepatitis B and C?
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IFN-alpha
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What is IFN-a used for?
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Chronic hepatitis B and C, Kaposi's sarcoma
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What is IFN-B used for?
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MS
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What is IFN-gamma used for?
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NADPH oxidase deficiency
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What are the toxicities for interferon?
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Neutropenia, Flu like sx on injection, neurotoxicity: somnolence and behavioral disturbances, severe fatigue and weight loss, autoimmune disorders (thyroiditis)
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What are the antibiotics to avoid in pregnancy?
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Sulfonamides (kernicterus), Aminoglycosides (ototoxicity), Fluoroquinolones (cartilage damage), Erythromycin (acute cholestatic hepatitis in moms - and clarithromycin - teratogenic), Metronidazole - mutagenesis, Tetracyclines - iscolored teeth, inhbiition of bone growth, Ribavirin - teratogenic, Griseofulvin - teratogenic, Chloramphenicol ("gray baby") - SAFE Moms Take Really Good Care
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