Antivirals II

Question 1

Simeprevir, Bocepravir, Telapravir are drugs used to treat HCV infection. They belong to which class?

Answer 1

NS3/4A protease inhibitors

Question 2

What is the mechanism of NS3/4A protease inhibitors?

Answer 2

Prevent Hepatitis viral maturation through inhibition of protein synthesis

Question 3

Sustained viral Response is treated

Answer 3

for 12 weeks and see if they stayed unresponsive and are cured

Question 4

Interferon for HCV-pegylated works by

Answer 4

Inducing interferon-stimulated genes (ISGs) that help establish an antiviral state within cells

Question 5

What were the toxicities acquired by Interferon Treatment?

Answer 5

Numerous toxicity concerns!!
Flu-like symptoms, Cytopenias, depression, fatigue
*Unstable psychiatric problems; baseline severe cytopenias

Question 6

Ribavirin major side effects?

Answer 6

Hemolytic anemia

Teratogenic

Question 7

Sofosbuvir belongs to a category of

Answer 7

Nucleoside/nucleotide NS5B POLYMERASE inhibitors

Question 8

MOA of Sofosbuvir?

Answer 8

Inhibitor of HCV NS5B RNA-dependent RNA polymerase. Once phosphorylated, competes with natural viral nucleotide (uridine) to cause chain termination of HCV RNA
*safe but it is still new

Question 9

Ledipasvir is sold in combo w. Sofosbuvir. Since Ledipasvir is a NS5A Inhibitor, what is its MOA?

Answer 9

Inhibits HCV NS5A, a viral phosphoprotein required for viral replication.
*safe

Question 10

Which drugs are the NS3/4A Protease Inhibitors?

Answer 10

Simeprevir, Boceprevir, Telaprevir

Question 11

What is the MOA of NS3/4A Protease Inhibitors

Answer 11

Prevent viral maturation through the inhibition of protein synthesis

*anemia, rash, itching, GI side effects, drug interactions

Question 12

MOA of Viral Guanosine Antivirals

Answer 12

Drug is using the viral Thymidine kinase to phosphorylate itself, acyclovir and penciclovir are only
phosphorylated in infected cells.

Question 13

Acyclovir (IV/PO/topical) covers

*prodrug is Valacyclovir (much more easily absorbed)

Answer 13

Herpes simplex 1+2

Varicella-zoster

Question 14

Penciclovir (IV,PO, topical)

*prodrug is Famciclovir (PO)

Answer 14

Herpes simplex 1+2

Varicella-zoster

Question 15

Ganciclovir (IV/PO)

*prodrug is Valganciclovir (PO)

Answer 15

Cytomegalovirus
Herpes simplex 1+2
Varicella-zoster

Question 16

Foscarnet spectrum of activity

Answer 16

Cytomegalovirus,
Herpes simplex 1+2
Varicella-zoster

Question 17

Toxicity of Acyclovir

Answer 17

Central nervous system - Malaise, headache, confusion
Nausea, vomiting, diarrhea
Renal dysfunction: only seen with higher doses of IV therapy due to drug crystallization in the kidney

Question 18

Toxicity of Valgancyclovir/Gancyclovir is

Answer 18

Myelosuppression (neutropenia 25-40% of patients)
Monitor CBC – may need to d/c drug
CNS toxicity (HA, seizures, confusion)
Hepatotoxicity, GI intolerance in limited patients

Question 19

Foscarnet MOA

Answer 19

MOA: directly inhibits herpesvirus DNA polymerase or HIV reverse transcriptase
Does not undergo significant intracellular metabolism so you don’t have to worry about resistance

Generally active against acyclovir / penciclovir /ganciclovir resistant viruses

Question 20

Toxicity of Foscarnet

Answer 20

Nephrotoxicity (occurs in 1/3 of patients)
Dose limiting side effects

Electrolyte/Metabolic abnormalities: (10-45% of patients)
Hypo / hypercalcemia
Hypo / hyperphosphatemia
Hypomagnesemia
Hypokalemia
Infuse at maximum rate of 1 mg/kg/minute to minimize these effects

CNS side effects (1/4 of patients)
Tremor, irritability, seizures (up to 10%), hallucinosis

Myelosuppression
***so you don’t give this drug unless you have to for resistant bugs

Question 21

Take home, which drug is best for Herpes Virus?

Gancyclovir is better for?

Answer 21

Acyclovir

—CMV

Question 22

Influenza Drugs -

Answer 22

Oseltamivir (Tamiflu) - prevents penetration and release of virus
Zanamivir (Relenza)
**active against both A/B
**must start w/in 2 days of symptoms

Question 23

Side Effects of Influenza Drugs

Answer 23

Oseltamavir:
GI side effects including nausea/vomiting/diarrhea
Neuropsychiatric events reported in older patients
Agitation, anxiety, altered mental status

Zanamavir-
Bronchospasm