Lecture 79 - Non HIV Anti-Virals

Question 1

• Neuramninidase Inhibitors

• Mechanism
• target
• the Drugs

Answer 1

Normal function of Neuraminidase: Hemaglutinnin of Influenza binds to Sialic Acid on the cell surface
Nueramidase cleaves this bond

Inhibitors: block Nueraminidase

Drugs:
Zanamavir – nasal spray
Oseltamivir – oral pro-drug

Question 2

Flu Vaccines:

Answer 2

Inactivated – A and B

Activated – (Live/attenuated)
Flumist
Reduces risk in kids by 92%

Question 3

IMP Dehydrogenase Inhibitors

• the drug
• The mechanism

Answer 3

Ribavirin –

Mechanism: structurally related to Guanosine. Monophospohated form inhibits IMP Dehdrogenase.
Inhibits formation for GTP and ATP

Question 4

USes of IMP Dehydrogenase Inhibitors:

Answer 4

Paramoxy viruses – RSV, parainfluenza virus (PIV); Arenavirus

Hep C Treatment: Ribavarin + pegylated interferons

Question 5

Acyclic/Carbocyclinc Nucleoside Analogs –

• drug names
• Spectrum

Answer 5

Acyclovir
Valacyclavir
Famciclovir
Ganciclovir

Herpes Virus,
CMV

Question 6

Acyclovir

• Mechanism
• Indications
• Pharamcology
• toxicity

Answer 6

Mechanism:
- 1) targets Viral Thymidine Kinase which phosphorylates aciclovir. Eventaully becomes tri-phospohorylated

2) The triphosphorylated drug inhibits Viral DNA polymerase by inserting itself into the nascent chain

Indications: HSV, VZV, Neonatal herpes

Pharmacology:
Good (oral) bioavailability
including CSF
excreted via kidneys and breast milk

Toxicity –
Encephalopathy in pt with renal insufficiency

Question 7

Valacyclovir

Answer 7

Valine ester of Aciclovir

Prodrug

Serum concentrations of ACV 3-5x higher with valcyclovir

Question 8

Famciclovir

• prodrug for what?
• mechanism?

Answer 8

Prodrug of Penciclovir

Same mechanism as acyclovir; but not as effective at inhibiting the viral polymerase

Minimal toxicity
good absorption

Question 9

Ganciclovir

• indications
• Mechanism
  Toxicity

Answer 9

Indications - used for lifethreatening cases of CMV;

Mechanism: same as aciclovir
Converted to MP from by UL97 in CMV

Toxicity – Bone marrow suppression (neutropenia, anemia, thrombocytopenia)

Question 10

Other nucleoside analogs:

Answer 10

Idoxuridine
Trifluridine
Flurorouracil

Question 11

FOSCARNET (Phosphonoformic acid)

• mechanism
• Spectrum

Answer 11

Mechanism:
Inhibits viral Polymerase, at site distinct from ACV binding site

Spectrum: HSV, CMV, HHV-6

Question 12

CIDOFOVIR – acyclic nucleoside phosphate

• indications
• Mechanism
• Pharmacology
• Toxicity

Answer 12

Indications: CMV Retinitis in AIDS patients

Mechanism: Molecule Monophosphorylated, eventually triphosphorylated, inhibits viral DNA polymerase (or the RT)

Pharm – renal excretion; long half life; IV admin

Toxicty –irreversible renal toxicity (given with Probenecid to protect the kidneys)

Question 13

Immunoglobulins – neutralizing antibodies

Answer 13

Prophylaxis: HAV; RSV

Therapy: rabies, HBV, CMV, Vaircella, Measales

Question 14

Antisense Oligonucleoties

• Drug name
• mechanism
• indication

Answer 14

• Vitravene

Complementary to RNA (antisense

Indication: Local injection of CMV retinitis in AIDS patients who are intolerant or have contra-indications to other treatments