Antiviral 1 - Influenza + Ribavarin Flashcards
Describe the common structure of influenza viruses
8 RNA strands encapsulated by Nucleoprotein (NP), virus-encoded polymerases (PA, PB1, PB2), and Matrix (M) protein below the plasma-derived lipid envelope
Describe the lipid membrane of influenza viruses
Host-derived lipid membrane with surface glycoproteins:
Hemagglutinin (HA) 18 subtypes
Neuraminidase (NA) 9 subtypes
True or False: There is no immune cross reactivity between influenza A, B, or C
True!
What part of the influenza virus binds to the target cell? What happens after it binds?
Haemagglutinin; endocytosis (brings virus into the cell)
Where does Amantadine work in the influenza life cycle?
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
What happens after the virus is endocytosed into the cell?
Fusion occurs, the cell is uncoated, the viral RNA enters the nucleus to make mRNA and produce proteins
Where does Ribavarin work in the influenza life cycle?
It blocks RNA polymerase to block viral DNA synthesis
What happens after the viral DNA is replicated?
It leaves the cell to form proteins to make a new cell, which is then released
Where does Zanamivir, Oseltamivir work?
Blocks sialidase (?) to block the release of the virus from the outside of the cell once a new virus forms
MOA of Amantadine, Rimantidine?
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
How are Amantadine, Rimantidine dosed?
Orally, 1-2 times daily for 5-7 days
In what patients are Amantadine, Rimantidine indicated?
Controls flu in institutionalized elderly patients
Adverse effects of Amantadine, Rimantidine?
GI disturbances
CNS - anxiety, headache, insomnia, hallucinations (more common in elderly)
Amantadine or Rimantidine: Which one has less CNS effects? Why?
Rimantidine has less bc it is less lipid soluble
How do Oseltamivir, Zanamivir, Peramivir work?
Selective inhibitors of influenza A and B viral neuraminidase enzyme blocks the release of virus from the cells.
How are Oseltamivir, Zanamivir, and Peramivir dosed?
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
Which drug was emergency approved in 2009 for H1N1 resistant to tamiflu?
Peramivir
What drugs are used in influenza A that is resistant to amantadine and rimantidine?
Oseltamivir, Zanamivir, or Peramivir
Indications for Oseltamivir, Zanamivir, and Peramivir?
Treatment and prophylaxis of influenza A and B in adults and children over 12 months (not babies!)
Adverse effects of Oseltamivir, Zanamivir, and Peramivir?
Oseltamivir: GI upset
Zanamivir: Wheezing and bronchospasm
Which drug should be avoided in pts with an underlying airway disease?
Zanamivir! causes wheezing and bronchospasm
What is Ribavirin?
A modified guanosine base with d-ribose sugar
Mechanism unknown; it inhibits viral messenger RNA synthesis. Given as IV and aerosol
How is Ribavirin dosed?
Oral, IV, inhalation (aerosol)
What is RIbavirin indicated for?
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
True or False: Ribavirin can be used for hepatitis C
False
Ribavirin + pegylated interferon alpha 2a or 2b was choice in hepatitis C, no longer reommended
Adverse effects of Ribavirin?
Anemia due to hemolysis Cardiac arrest Hypotension Seizures Mood changes Suicide Apnea Bronchospasm (aerosol)
Which drug requires high monitoring for women who may become pregnant? What is the monitoring?
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
