54-Antiviral Drugs

Question 1

Acyclovir

MOA, resistance, use, adverse

Answer 1

nucleoside analoue is phosphorylated by viral thymidine kinase enzyme that blocks DNA synthesis
mutation of thymidine kinase gene (cross resistance with other similar antivirals)
Oral for genital herpes or varicella zoster; IV for severe
reversible crystalline nephrotoxicity that is exacerbated by dehydration

Question 2

Valacyclovir (use)

Answer 2

prodrug of acyclovir that is metabolized by liver and intestines
oral only for herpes, varicella

Question 3

Foscarnet (MOA, use, adverse)

Answer 3

blocks pyrophosphate release (doesn’t require thymidine kinase so can use in acyclovir resistant patients) IV ONLY
HSV an VZV resistant to acyclovir; CMV everything
changes in blood chemistry, avoid co-administration of nephrotoxic agents because this slows down kidneys

Question 4

Ganciclovir (MOA, resistance, use, adverse)

Answer 4

guanosine analogue that requires initial phosphorylation by viral kinase. Phosphorylated by CMV UL97 much better than acyclovir (thus way more effective)
mutation of UL97 gene
CMV stuff
bone marrow and CNS toxicity

Question 5

Valganciclovir

Answer 5

prodrug of ganciclovir with much better oral bioavailability

CMV with transplant patients

Question 6

Trifluridine (MOA, use)

Answer 6

fluorinated nucloside phosphorylated by cellular enzymes

low selectivity means only local administration

Question 7

Oseltamivir (MOA, use)

Answer 7

sialic acid analogue binds to neuraminidase to block efficient release of virions
give in first 48 hours of flu or later if complicated

Question 8

Zanamivir (MOA, use)

Answer 8

inhalable neuraminidase inhibitor (sialic acid analogue like oseltamivir)
kids 7 and up
can cause pulmonary problems

Question 9

Amantadine and Rimantadine

MOA, resistance, use

Answer 9

tricyclic amines that inhibit infuenza A M2 protein required for injecting genetic material into cell
amino acid substitutions in M2 protein
limited use now, but used to be given within 48 hours of flu symptoms

Question 10

Ribavirin (MOA, use, adverse)

Answer 10

guanosine analogue that is phosphoylated by cellular adenosine kinase and inhibits mRNA in RSV and Hep C virus
aerosol for RSV or orally for Hep C
can cause hemolytic anemia

Question 11

What drug for what genotypes of Hep C treatments?

Answer 11

1,4,5,6 get ribavirin, interferon and sofosbuvir

2,3 get sofosbuvir and ribavirin

Question 12

Interferon (MOA, adverse)

Answer 12

pegylated cytokine (attached to inert molecule to slow clearance) that signals IFN receptors and Jak/Stat pathways to invoke "antiviral state" in cells
flu-like symptoms

Question 13

Sofosbuvir (MOA, use, adverse)

Answer 13

nucleic acid prodrug that blocks RNA termination
NOT FOR MONOTHERAPY
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