Anti-influenza agents

1. Antiviral drugs
Anti-Influenza agents
S. Parasuraman, M.Pharm., Ph.D.,
Associate Professor
Faculty of Pharmacy
AIMST University, Malaysia

2. Anti-Influenza agents - Learning Outcomes
• At the end of this session, the student would be able
to:
– list the drugs used for the management of influenza virus
infection. (CLO1)
– describe the mechanism of action, pharmacological
actions, pharmacokinetic features, therapeutic uses,
adverse effects, interaction and contraindications of anti-
influenza drugs. (CLO1)

3. Influenza virus and Anti-Influenza agents
• Three types of flu viruses: A, B, and C
• Type A flu or influenza A viruses are capable of infecting
animals, although it is more common for people to suffer the
ailments associated with this type of flu. Wild birds commonly
act as the hosts for this flu virus.
– Strains of influenza A: H5N1 (avian influenza/bird
flu) and H1N1 (swine flu).
• Unlike type A flu viruses, type B flu is found only in humans.
Type B flu may cause a less severe reaction than type A flu
virus, but occasionally, type B flu can still be extremely
harmful.
• Influenza C viruses are also found in people. They are,
however, milder than either type A or B. People generally do
not become very ill from the influenza type C viruses.
Reference: https://www.webmd.com/cold-and-flu/advanced-reading-types-of-flu-viruses#1; Last assessed on 20/03/2020

4. Influenza virus and Anti-Influenza agents
• Amantadine
– Inhibits replication of influenza A virus. The antiviral
activity of amantadine is strain specific; influenza B is
not affected.
– Amantadine is well absorbed orally and excreted
unchanged in urine over 2–3 days (t½ 16 hr).
– ADR: Generally well tolerated; nausea, anorexia,
insomnia, dizziness, nightmares, lack of mental
concentration, rarely hallucinations have been
reported. Ankle edema occurs due to local
vasoconstriction.
Anti-Influenza virus: Amantadine, Rimantadine,
Oseltamivir, Zanamivir

5. Influenza virus and Anti-Influenza agents
• Amantadine
• Uses:
– Prophylaxis of influenza A2: Only when the epidemic
causing strain of virus is known to be sensitive to
amantadine, should prophylactic use be considered,
especially in high risk patients. Amantadine is no longer
recommended in UK, either for prophylaxis or for treatment
of influenza.
– Treatment of influenzal (A2) illness: A modest therapeutic
effect (reduction in fever, congestion, cough and quicker
recovery) occurs if the drug is given immediately after the
symptoms appear. A 5 day treatment is advised.
– Parkinsonism

6. Influenza virus and Anti-Influenza agents
Rimantadine
• This methyl derivative of amantadine is more potent,
longer acting (t½ 30 hours) and better tolerated than the
parent drug.
• Dose and clinical application in influenza A is similar to
amantadine and it is being preferred over the latter.
However, amantadine resistant virus is resistant to
rimantadine as well.

7. Influenza virus and Anti-Influenza agents
Oseltamivir
• This newer anti-influenza virus drug is a sialic acid
analogue with broad spectrum activity covering influenza
A (amantadine sensitive as well as resistant), H5N1 (bird
flu), nH1N1 (swine flu) strains and influenza B.
• PK: oral bioavailability of ~ 80%. The active metabolite is
not further metabolized and is excreted by the kidney
with a t½ of 6–10 hours.
• MOA: It acts by inhibiting influenza virus neuraminidase
enzyme which is needed for release of progeny virions
from the infected cell.

8. Influenza virus and Anti-Influenza agents
Oseltamivir
• Use:
– Oseltamivir is indicated both for prophylaxis as well as
treatment of influenza A, swine flu, bird flu and influenza
B.
– Prophylactic use for 5–10 days prevents illness in contacts
of influenza patients.
• ADR:
– Nausea, abdominal pain, headache, weakness, sadness,
diarrhoea, cough, insomnia, skin reactions

9. Influenza virus and Anti-Influenza agents
Zanamivir
• Zanamivir is influenza A (including amantadine-resistant,
nH1N1, H5N1 strains) and influenza B virus
neuraminidase inhibitor.
• Clinical utility and efficacy of zanamivir are similar to that
of oseltamivir.
• The inhaled powder can induce bronchospasm in some
individuals. Contraindicated in asthmatic patients.