Antiviral 1 - Influenza + Ribavarin

Question 1

Describe the common structure of influenza viruses

Answer 1

8 RNA strands encapsulated by Nucleoprotein (NP), virus-encoded polymerases (PA, PB1, PB2), and Matrix (M) protein below the plasma-derived lipid envelope

Question 2

Describe the lipid membrane of influenza viruses

Answer 2

Host-derived lipid membrane with surface glycoproteins:
Hemagglutinin (HA) 18 subtypes
Neuraminidase (NA) 9 subtypes

Question 3

True or False: There is no immune cross reactivity between influenza A, B, or C

Answer 3

True!

Question 4

What part of the influenza virus binds to the target cell? What happens after it binds?

Answer 4

Haemagglutinin; endocytosis (brings virus into the cell)

Question 5

Where does Amantadine work in the influenza life cycle?

Answer 5

2 places: It blocks M2, haemagluttinin to block uncoating of the virus once it’s endocytosed

also Blocks M2 to block protein synthesis of the new virus

Question 6

What happens after the virus is endocytosed into the cell?

Answer 6

Fusion occurs, the cell is uncoated, the viral RNA enters the nucleus to make mRNA and produce proteins

Question 7

Where does Ribavarin work in the influenza life cycle?

Answer 7

It blocks RNA polymerase to block viral DNA synthesis

Question 8

What happens after the viral DNA is replicated?

Answer 8

It leaves the cell to form proteins to make a new cell, which is then released

Question 9

Where does Zanamivir, Oseltamivir work?

Answer 9

Blocks sialidase (?) to block the release of the virus from the outside of the cell once a new virus forms

Question 10

MOA of Amantadine, Rimantidine?

Answer 10

Blocks M2 ion channel which blocks the uncoating of Influenza A, NOT INFLUENZA B!!!

Also alters the pH of the endosome to prevent uncoating of the viral material

Question 11

How are Amantadine, Rimantidine dosed?

Answer 11

Orally, 1-2 times daily for 5-7 days

Question 12

In what patients are Amantadine, Rimantidine indicated?

Answer 12

Controls flu in institutionalized elderly patients

Question 13

Adverse effects of Amantadine, Rimantidine?

Answer 13

GI disturbances

CNS - anxiety, headache, insomnia, hallucinations (more common in elderly)

Question 14

Amantadine or Rimantidine: Which one has less CNS effects? Why?

Answer 14

Rimantidine has less bc it is less lipid soluble

Question 15

How do Oseltamivir, Zanamivir, Peramivir work?

Answer 15

Selective inhibitors of influenza A and B viral neuraminidase enzyme blocks the release of virus from the cells.

Question 16

How are Oseltamivir, Zanamivir, and Peramivir dosed?

Answer 16

Oseltamivir: oral tablets and suspensions
Zanamivir: Dry powder inhaler
Peramivir: Single dose IV infusion

Must be given within 48 hours of onset of symptoms, shortens disease by 24 hours

Question 17

Which drug was emergency approved in 2009 for H1N1 resistant to tamiflu?

Answer 17

Peramivir

Question 18

What drugs are used in influenza A that is resistant to amantadine and rimantidine?

Answer 18

Oseltamivir, Zanamivir, or Peramivir

Question 19

Indications for Oseltamivir, Zanamivir, and Peramivir?

Answer 19

Treatment and prophylaxis of influenza A and B in adults and children over 12 months (not babies!)

Question 20

Adverse effects of Oseltamivir, Zanamivir, and Peramivir?

Answer 20

Oseltamivir: GI upset

Zanamivir: Wheezing and bronchospasm

Question 21

Which drug should be avoided in pts with an underlying airway disease?

Answer 21

Zanamivir! causes wheezing and bronchospasm

Question 22

What is Ribavirin?

Answer 22

A modified guanosine base with d-ribose sugar

Mechanism unknown; it inhibits viral messenger RNA synthesis. Given as IV and aerosol

Question 23

How is Ribavirin dosed?

Answer 23

Oral, IV, inhalation (aerosol)

Question 24

What is RIbavirin indicated for?

Answer 24

Effective against Adenovirus, Colorado tick virus, hepatitis C, Herpes virus, mumps virus, Rift valley virus, yellow fever virus, Hantavirus, Crimean-Congo hemorrhagic virus

FDA approved for respiratory syncytial virus in children

Also used in immune suppressed pts

Question 25

True or False: Ribavirin can be used for hepatitis C

Answer 25

False

Ribavirin + pegylated interferon alpha 2a or 2b was choice in hepatitis C, no longer reommended

Question 26

Adverse effects of Ribavirin?

Answer 26

Anemia due to hemolysis
Cardiac arrest
Hypotension
Seizures
Mood changes
Suicide
Apnea
Bronchospasm (aerosol)

Question 27

Which drug requires high monitoring for women who may become pregnant? What is the monitoring?

Answer 27

Ribavirin
Teratogenic in animals
2 types of contraceptives during and for 6 months after therapy
Do not use in women OR men trying to get pregnant