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Antiviral Drugs
n/a
16
Microbiology
11/20/2011

Additional Microbiology Flashcards

 


 

Cards

Term
Gancyclovir
Definition
  • nucleoside analog of guanosine 
  • 50x higher activity against CMV 
  • Needs a virally encoded phosphorylating agent, found in CMV infected cells to become an active monophosphate 
  • Valganciclovir is the L-valyl ester prodrug of ganciclovir 
  • Neutropenia and thrombocytopenia are side effects 
  • similar to acyclovir but has an additional hydroxymethyl group on acyclic side chain
Term
Cidofovir
Definition
  • Cytidine nucleoside analogue for herpesviruses 
  • metabolized to its active diphosphate form by cellular enzymes 
  • diphosphate active form actes as both a competitive inhibitor w.r.t dCTP and as an alternative substrate for viral DNA polymerase
  • Resistance in CMV is due to mutations in viral DNA polymerase 
  • excreted mainly through the kidneys 
  • nephrotoxic
  • only used against CMV in case of failure of other drugs
Term
Ribavirin
Definition
  • nucleotide analogue
  • inhibitor of RNA synthesis
  • needs to be phophorylated to become active
  • mechanism incompletely understood:
    • alters cellular nucleotide pool
    • inhibits viral mRNA synthesis
  • intracellular phosphorylation into mono-,di-,and triphophate derivatives by host cell enzymes
    • monophosphate: competitvely inhibits cellular inosine 5' phophate dehydrogenase and interferes with synthesis of GTP
    • triphosphate: competitively inhibits GTP-dependent 5' capping of viral mRNA, inhibits RNA polymerase
  • for treatment of HCV in combination with interferon
  • aerosol for RSV infection in children 
Term
Amantadine and rimantadine
Definition
  • Hydrophobic amines (weak organic bases) inhibit the ion channel function of the M2 protein of influenza A viruses
  • By blocking proton permeation and prevent M2-mediated changes in pH
    • inhibition of the acid-mediated dissociation of the matrix protein from the ribonucleoprotein complex within endosomes early in replication
    • Inhibits several steps in early replication
  • Only oral preparations
  • Amantadine excreted by the kidney without metabolism
  • Rimantadine: metabolized through the liver

 

Term
Oseltamivir
Definition
  • Neuraminidase inhibitor
  • Oral oseltamivir is effective in the treatment and prevention of influenza A and B virus infections.
  • reduces illness duration by about 1 to 2 days
  • reduces the risk of complications leading to antibiotic use by 40% to 50%
  • Treatment is associated with approximate halving of the risk of subsequent hospitalization in adults
  • When used for prophylaxis during the influenza season, oseltamivir (75 mg once daily) is effective (approximately 70% to 90%) in reducing the likelihood of influenza illness in both unimmunized working adults and in immunized nursing home residents
  • short-term use (7 to 10 days) protects against influenza in household contacts
Term
Acyclovir
Definition
  • Guanosine analog
  • 3-carbon acylic carbon instead of cyclic ribose
  • Needs to be phophorylated by thimidine kinase to be active.
  • Phosphorylation occurs only in cells infected by
  • certain herpes viruses that induce the thymidine kinase
  • 100th fold greater affinity of acyclovir to viral DNA polymerase than for cellular DNA polymerase
  • Inhibits viral DNA polymerase and terminates viral DNA chain growth.
  • Does not eliminate the virus from the host
  • Formulations:
    • Oral
    • Topical
    • Parenteral
  • Used for Herpes Simplex Virus type 1 and 2 as well as Varicella Zoster Virus
  • Valacyclovir is a prodrug of acyclovir that is better absorbed
Term
Interferon
Definition

 

  • IFN-α and IFN-β exhibit antiviral and antiproliferative actions:
    • stimulate cytotoxic activity of lymphocytes, NK cells, and macrophages
    • up-regulate MHC I  and other surface markers
  • IFNγ- less antiviral activity but more potent immunoregulatory effects:
    • macrophage activation
    • expression of MHC II  
    • mediation of local inflammatory responses
  • The binding of IFN to specific cell surface receptor molecules signals the cell to produce a series of antiviral proteins
  • Clinical use: Only IV
  • Attachment of IFN proteins to large, inert polyethylene glycol(PEG) molecules (pegylation):
    • slows absorption
    • decreases clearance
    • provides higher and more prolonged serum concentrations
      • enable once-weekly dosing
  • IFN α: Used in treatment of HCV, HBV, Kaposi sarcoma, cancer (ex. Lymphoma)
  • IFN β: Multiple sclerosis

 

Term
Anti-retroviral
Definition
  • Entry inhibitors
  • Nucleoside and nucleotide reverse transcriptase inhibitors
  • Non-nucleoside reverse transcriptase inhibitors
  • Integrase inhibitors
  • HIV protease inhibitors
Term
Enfuviritide
Definition
  • anti retroviral
  • Inhibits penetration and unoating
  • Inhibits the action of the viral fusion protein gp41, stops conformational change
Term
Maraviroc
Definition
  • anti retroviral
  • Inhibits penetration and uncoating
  • Inhibits CCR5 coreceptor
Term

Nuleotide and nucleoside reverse transcriptase inhibitors

NRTI

Definition
  • anti retroviral
  • Like all nucleoside analogs, they need to be phosphorylated to be integraed in the growing chain
Term
Non-nucleoside polymerase inhibitors
Definition
  • anti retroviral
  • bind to a hydrophobic pocket in the p66 subunit of the HIV-1 reverse transcriptase
  • These compounds induce a conformational change in the 3-D structure of the enzyme that greatly reduces its activity
  • act as noncompetitive inhibitors
Term
Raltegravir
Definition
  • anti retroviral
  • integrase inhibitor
  • inhibits the catalytic activity of integrase, preventing integration of the proviral gene into human DNA
Term
Protease inhibitor
Definition
  • anti retroviral
  • peptide like chemicals that competitively inhibit the action of the virus protease that cleaves polyproteins into structural proteins
Term
Foscarnet
Definition
  • Inhibits DNA polymerase
  • CMV, HSV, VZV
Term
anti HBV
Definition
  • Lamivudine, adefovir, entecavir,
  • Tenofovir
  • Interferon