Antivirals

Question 0

Zanamirvir

Answer 0

• MOA: Inhibit influenza neuraminidase, decreasing the release of progeny virus
• Use: Both influenza A & B

Question 1

Amantadine

Answer 1

• MOA: Blocks viral penetration/uncoating (M2 protein)
  
  1. Also causes release of dopamine in intact nerve terminals
• Use: prophylaxis & Tx for influenza A
  
  1. Parkinson’s disease
• Toxicity: Ataxia, dizzy, slurred speech
• Resistance: Mutated M2 protein; 90% flu A resistant

Question 2

Oseltamivir

Answer 2

• MOA: Inhibit influenza neuraminidase, decreasing the release of progeny virus
• Use: Both influenza A & B

Question 3

Ribavirin

Answer 3

• MOA: inhibits synth of guanine nucleotides by competitively inhibiting IMP dehydrogenase
• Use: RSV, chronic hepatitis C
• Toxicity: hemolytic anemia, severe teratogen

Question 4

Acyclovir

Answer 4

• MOA: Monophosphorylated by HSV/VZV thymidine kinase
  
  1. Guanosine analog
  2. Triphosphate formed by cellular enzymes
  3. Inhibits viral DNA polymerase by chain termination
• Use: HSV, VZV, EBV
  
  1. HSV-induced mucocutaneous/genital lesions, encephalitis
  2. No effect on latent HSV or VZV
• Toxicity: few
• Resistance: lack of viral thymidine kinase

Question 5

Valacyclovir

Answer 5

• Prodrug of acyclovir
• MOA: Monophosphorylated by HSV/VZV thymidine kinase
  
  1. Guanosine analog
  2. Triphosphate formed by cellular enzymes
  3. Inhibits viral DNA polymerase by chain termination
• Use: HSV, VZV, EBV
  
  1. HSV-induced mucocutaneous/genital lesions, encephalitis
  2. No effect on latent HSV or VZV
• Toxicity: few
• Resistance: lack of viral thymidine kinase

Question 6

Famciclovir

Answer 6

• Related to Acyclovir; Used for herpes zoster
• MOA: Monophosphorylated by HSV/VZV thymidine kinase
  
  1. Guanosine analog
  2. Triphosphate formed by cellular enzymes
  3. Inhibits viral DNA polymerase by chain termination
• Use: HSV, VZV, EBV
  
  1. HSV-induced mucocutaneous/genital lesions, encephalitis
  2. No effect on latent HSV or VZV
• Toxicity: few
• Resistance: lack of viral thymidine kinase

Question 7

Ganciclovir

Answer 7

• MOA: 5’-monophosphate formed by CMV viral kinase
  
  1. Guanosine analog
  2. Triphosphate formed by cellular kinases
  3. Inhibits viral DNA polymerase
• Use: CMV esp in immunocompromised patients
• Toxicity: Leukopenia, neutropenia, thrombocytopenia, renal tox
• Resistance: mutated CMV DNA polymerase or lack of viral kinase

Question 8

Valganciclovir

Answer 8

• Prodrug of ganciclovir
• MOA: 5’-monophosphate formed by CMV viral kinase
  
  1. Guanosine analog
  2. Triphosphate formed by cellular kinases
  3. Inhibits viral DNA polymerase
• Use: CMV esp in immunocompromised patients
• Toxicity: Leukopenia, neutropenia, thrombocytopenia, renal tox
• Resistance: mutated CMV DNA polymerase or lack of viral kinase

Question 9

Foscarnet

Answer 9

• MOA: Pyrophosphate analogue
  
  1. Binds pyrophosphate site on DNA polymerase
  2. inhibits polymerase and blocks DNA chain elongation
  3. No viral kinase needed
• Use: CMV retinitis in immunocompromised patients when ganciclovir fails; acyclovir resistant HSV
• Toxicity: Nephotoxicity
• Resistance: mutated DNA polymerase

Question 10

Cidofovir

Answer 10

• MOA: Monophosphate nucleotide analogue
  
  1. inhibits viral DNA polymerase- prevents DNA chain elongation
  2. Does NOT require phosphorylase by viral kinase
• Use: CMV retinitis in immunocompromised patients; acyclovir resistant HSV
• Toxicity: Nephrotoxicity, coadminister w/ probenecid

Question 11

Interferons

Answer 11

• MOA: Glycoproteins synthesized by virus-infected cells block replication of both RNA and DNA viruses
• Use:
  
  1. IFN-alpha: chronic hepatitis B & C, Kaposi’s sarcoma
  2. IFN-beta: MS
  3. IFN-gamma: NADPH oxidase deficiency
• Toxicity: Neutropenia