anti-influenza agents

exam 3

influenza

responsible for millions of deaths worldwide

influenza

attacks mainly the upper respiratory tract and poses a serious risk for elderly adults, young children, and people with underlying medical conditions such as lung, kidney, or heart problems, diabetes, cancer or immunosuppression

yearly challenge

antigenic changes in the viral surface glycoproteins make effective vaccination a

influenza 

there are 2 classes of drugs and 4 individual agents used for 

sialic acid

influenza virus attaches to cell surface

hemagglutinin (HA)

flue virus attaches to cell surface sialic acid via the receptor site located on top of large globule of the

internalized and uncoated for replication

after virus attaches its particles are

internalized and uncoated 

for influenza virus replication to happen virus particles must be 

surface of the cell

after replication of genetic material the flue virus matures by budding from the

neuraminidase (NA)

removes terminal sialic acids from cellular and viral surface glycoproteins, facilitating release of virus particles form the cell and preventing aggregation

neuraminidase

facilitates release of virus particles form the cell to prevent aggregation

influenza A 

divided into subtypes based on 2 proteins on surface of virus - hemagglutinin and neuraminidase

18 subtypes

hemagglutinin (H) has

11 subtypes

neuraminidase (N) has

type B strain

in 2024-2025 influenza vaccine will contain H1N1 and H3N2 strains with

population surveillance data 

different combinations of vaccine are selected to create yearly vaccine based on 

prevention/treatment of influenza

2 classes of antiviral drugs are available for the

influenza A and B

neuraminidase inhibitors, zanamivir, oseltamivir, and peramivir are active against

influenza A and B

the selective inhibitor of influenza cap dependent endonuclease, baloxavir are active against

new virions

neuraminidase inhibitors prevent release of 

neuraminidase inhibitors

structurally related drugs approved for the prophylaxis and treatment of influenza

neuraminidase inhibitors

approved for treatment of acute uncomplicated influenza in patients who have been symptomatic for over 48 hours

neuraminidase inhibitor

interfere with the release of progeny influenza virus from infected cells, preventing new rounds of infection

progeny virions 

are bound to the host cell via sialic acid residues on cell surface glycoproteins 

pregeny virions

neuraminidase mediated removal of these sialic acid moieties permits release of

sialic acid analogs

zanamivir, oseltamivir, and peramivir are

competitively inhibit neuraminidase on surface of influenza A and B

zanamivir, oseltamivir, and permivir are sialic acid analogs that

Tamiflu 

oseltoseltamivir trade name 

orally BID and liquid depends on use

oseltamivir is an oral capsule and powder for liquid suspension that is dosed

nausea and vomiting

oseltamivir is well tolerated but can cause

Relenza Diskhaler

trade name of zanamivir

inhaled powder 

zanamivir is an 

2 inhalations once or twice daily (frequency and duration depends on use)

dosing of zanamivir

aggravate pulmonary conditions

zanamivir is well tolerated but it may

Rapivab

trade name of peramivir

single dose 

peramivir is given intravenously with a 

diarrhea, elevated glucose, and neutropenia

adverse affects of peramivir

oseltamivir

has serious ADEs in post marketing surveillance

usually transient and doesnt require discontinuation

GI distress due to oseltamivir

oseltamivir 

has neuropsychiatric effects in children and adolescents

flu infection rather than drug

causation of neuropsychiatric effects in patients using oseltamivir is not established the effects like confusion, delirium, hallucination, and self harm may be linked to

baloxavir

a novel oral prodrug

Xofluza

trade name of baloxavir

baloxavir (Xofluza) 

selective inhibitor cap dependent endonuclease that blocks influenza proliferation by inhibiting initiation of mRNA synthesis 

baloxavir (Xofluza)

activity against influenza viruses that are resistant to oseltamivir

neuraminidase inhibitors

baloxavir/ Xofluza appears to have synergistic activity with

96 hours

baloxavir (Xofluza) is given as single dose with a mean elimination half life of

why flu vaccines repeated every year 

HA and Na undergo frequent antigenic changes independent of each other 

antigenic variants of influenza virus

have a selective advantage over the parental virus in the presence of antibody directed against the original strain

antigenic shifts

influenza vaccines are repeated yearly due to HA and NA going through

COIVD 19 antivirals

remdesivir, molnupiravir, and nirmatrelvir/ritonavir

remdesivir 

FDA COVID 19 antiviral that inhibits SARS-CoV-2 RNA dependent RNA polymerase 

Veklury

trade name of remdesivir

remdesivir

COVID 19 antiviral andenosine analog

molnupiravir

not FDA approved only for emergency use authorization and is inhibitor of SARS-CoV-2 RNA dependent RNA polymerase

Lagevrio 

trade name of molnupiravir 

molnupiravir

a COVID 19 antiviral that is a cytosine analog

nirmatrelvir/ritonavir

FDA approved COVID 19 antiviral that is SARS-COV-2 protease inhibitor

Paxlovid

trade name of nirmatrlvir/ritonavir