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Flashcards in Multi-Systems: Antiviral Agents Deck (56)
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1

(2) Anti-herpes-viral drugs that are Guanosine analogs that
inhibit Nucleic Acid Synthesis?

Acyclovir (HSV, VZV)

Ganciclovir (CMV)

2

Mechanism of Acyclovir and Ganciclovir?

  • Acts as a Chain terminator and Viral DNA Polymerase Inhibitor (HSV-enzyme required to activate)
  • Guanosine analog w/ Acyclic Sugar
  • Phosphorylated by Viral Thymidine Kinase 
    --> acylcoGMP --> acycloGTP
  • Valacyclovir + H2O --> Acyclovir + Valine
  • Valganciclovir + H2O --> Ganciclovir + Valine

3

Clinical use of Acyclovir and Ganciclovir?

  • Acyclovir
    • HSV-1, HSV-2
    • VZV
    • EBV
  • Ganciclovir
    • CMV
    • HHV-6, HHV-7

4

Resistance to Acyclovir and Ganciclover?

  • Deleted or Mutated - Viral Tyrosine Kinase
  • Resistant - Viral DNA Polymerase
  • No effect during latent infection because Viral Tyrosine Kinase is not expressed

5

Drugs that work on CMV?

  • Ganciclovir (Guanosine analog)
  • Foscarnet (Viral DNA polymerase inhibitor)

6

(2) Anti-herpes-viral, Viral DNA polymerase inhibitors that stop Nucleid Acid Synthesis?

  • Foscarnet (CMV)
  • Cidofovir (HSV* - Acyclovir resistant)

7

Mechanism of Foscarnet?

  • An inorganic pyrophospate analog that Inhibits Viral DNA polymerase w/out requireng activation via Phosphorylation by Viral Kinases.
  • Effective against resistant strains of HSV, VSV, and CMV

8

Clinical use of Foscarnet?

  • Acyclovir-resistant HSV and VZV
  • Ganciclovir-resistant CMV
    • Produces less Bone Marrow suppression than Ganciclovir

9

SEs of Foscarnet?

  • Nephrotoxicity
  • Foscarnet acts as a Potent Chelator of divalent Cations
    --> decreased ionized Ca2+, Mg2+ 
    --> Symptomatic Hypocalcemia w/ normal Serum Ca2+

10

Resistance to Foscarnet?

  • Foscarnet binds to the pyrophosphate binding site of the DNA polymerase
    --> Mutations in DNA Polymerase that prevent binding 

11

(2) Antiviral drugs that Block the
Influenza A M2 Protein Channel

--> Preventing Uncoating of Influenza virion
--> Req'd for Infection

  • Amantadine
  • Rimantadine

12

Mechanism of Amantadine and Rimantadine?

  • M2 channel conducts Protons from the Endosome into the Virion
    --> Acidification of the Interior and Dissociation of the Matrix protein from Viral ribonucleoproteins (RNPs)
  • Amantadine / Rimantadine prevent Virion from fusing w/ the Endosomal membrane and stops from Releasing contents into Cytoplasm

13

Clinical use of Amantadine and Rimantadine?

  • Influenza A infections
  • No longer used though due to increased Resistance
  • Resistance arises rapidly via Single-point mutation of M2 protein

14

(1) Hepatitis Anti-viral, Guanine nucleotide Synthesis that Inhibits Nucleic Acid Synthesis?

  • Ribavirin

15

Mechanism of Ribavirin?

  • Guanosine analog that is Phosphorylated by Cellular enzymes
  • Inhibits Syn. of Guanine Nucleotides by competitively inhibiting Inosine Monophosphate Dehydrogenase
  • Inhibits IMP dehydrogenase
    --> Impaired Purine synthesis
  • Inhibits Viral RNA polymerase and  5' cap formation on mRNAs

16

Clinical use of Ribavirin?

  • Chronic HCV Infection (in combination w/ IFN-α)

17

SEs of Ribavirin?

  • Hemolytic anemia when administered IV
  • Severe Teratogenic
  • Oncogenic
  • Gonadotoxic

18

Small polypeptide (18 kd) that binds to a cellular receptor
and Induces a Antiviral Cellular State?

  • IFN-α

19

Mechanism of IFN-α?

  • Binds to Cellular Receptor and Induces a Antiviral Cellular State
    1. ​Phosph. of EF 2 --> Inhibit Peptide Chain Initiation
    2. Ribonuclease Activation --> degrade Viral mRNA
    3. Phosphodiesterase exp --> degrade tRNAs
      --> inhibit Peptide Chain Elongation
    4. Increase Natural killer cell lytic function
    5. Increase exp. of MHC Class I molecules

20

Clinical use of IFN-α?

  • Chronic Hepatitis B and Hepatitis C Infections
  • Anti-tumor effect on various cancers
    • Melanoma
    • Hairy cell leukemia
    • Kaposi's Sarcoma

21

SEs of IFN-α?

  • Flu-like Symptoms
    • Fever
    • Myalgias
    • Malaise
  • Neutropenia
  • Thrombocytopenia

22

(2) Drugs that Reversibly Inhibit Neuraminidase (NA)
of Influenza A and B and impairs budding of Virions?

  • Zanamivir
  • Oseltamivir

23

SEs of Zanamivir and Oseltamivir?

  • Bronchospasm
  • Oseltamivir (Tamiflu) is a prodrug that is converted by the Liver to an Active neuraminidase Inhibitor after Oral Administartion
    • Used for Treatment and Prophylaxis of Influenza A and Influenza B Infections.

24

Mechanism of Enfuvirtide?

  • Polypeptide Fusion inhibitor
  • Binds to the First Heptad-repeat (HR1) in the 
    gp41 subunit of the HIV envelope glycoprotein and
    Prevents the Conformational changes Req'd for the Fusion of Viral and Cellular membranes
  • HIV is prevented from establishing infection in the Target Cell.

25

Clinical use of Enfuvirtide?

  • HIV infection
  • Salvage regimens to treat Multi-drug-resistant HIV

26

(3) Drugs that are Fusion Inhibitors?

  1. Maraviroc (HIV - CCR5 as a co-receptor)
  2. Enfuvirtide (HIV - gp41 HRI region)
  3. Palivizumab (RSV)

27

Mechanism of Maraviroc?

  • This entry inhibitor Binds to the CCR5 Receptor on
    MacrophagesT cells, and Dendritic cells
  • Prevents HIV from using CCR5 as a co-Receptor
  • Blocks entry of CCR5-trophic HIV into cells

28

Clinical use of Maraviroc?

  • HIV Infection
  • Primarly to salvage regiments of multi-drug-resistant HIV
  • Prior to intiation of Therapy, a Viral tropism assay should be done to Exclude CXCR4 or dual trophic HIV Infection

29

SEs of Maraviroc?

  • Cardiovascular
    • Myocardial Ischemia
    • Myocardial Infarction

30

Mechanism of Raltegravir?

  • An Integrase inhibitor that reversibly
    Inhibits HIV Integrase --> Preventing the HIV genome from being inserted into the Host cell Chromosome.