Influenza can be type A, B or C depending upon type. Influenza A and B are more common. Effective drugs have been discovered.
Life cycle
After binding host cell, fusion and entry occurs, gene is transferred, nucleic acid component is produced, leading to release of virus.
Two additional components are present:
1. Heme agglutinin
Influenza virus binds heme agglutinin on host cell epithelial surface specifically respiratory tract.
2. Neuraminidase on surface
Enzymes present within influenza virus on surface and enhance cleavage of newly formed mature virus components. These are cleaved and released to infect others, neuraminidase facilitates.
Mechanism of action
Basis of mechanism of action of most anti-influenzal agents are same, hemeagglutination, others neuraminidase.
A number of strains of humans and animals were endemic in 2003 and beyond resistant strains were discovered. H5, N1, swine flu and there is fear that transmission might occur.
Amantadine/Rimantadine
Specifically for influenza A virus. Bind M2 proteins, necessary for fusion of viral membrane to cell membrane, as a result fusion does not take place.
Some effects are also seen against release of new virions.
Mechanism of Action:
- Active against influenza A virus only.
- These drugs block M2 proteins that act as an ion channel, and necessary for fusion of viral membrane to the cell membrane.
- Also interfere with release of new virions.
Pharmacokinetics:
- Orally, well absorbed .
- Amantadine well distributed including CNS, Rimantadine does not cross BBB to same extent.
- Amantadine excreted unmetabolized in urine, Rimantadine undergoes extensive metabolism by hydroxylation, conjugation, glucuronidation before urinary excretion.
- T ½ = 12 – 18 hrs for Amantadine while it is 24 – 36 hrs for Rimantadine
Adverse effects
Amantadine:
- Insomia,
- dizziness,
- ataxia,
- nervousness,
- light headedness.
Rimantadine:
- causes fewer CNS disturbances.
- contraindicated in pregnant and lactating women.
| Amantadine | Rimantidine | |
| Half life | 12-18 hours | 36 hours |
| PPB | 67% | 14% |
| Metabolism | Not metabolized | Extensively metabolized |
| Excretion in urine | Unchanged | Metabolite form |
| ADRs | As readily cross BBB, most troublesome CNS related:InsomniaDizzinessAtaxiaNervousnessLight headedness | Cause fewer CNS disturbances |
Zanamivir & Oseltamivir
Active against both influenza A & B.
Mechanism of Action:
They inhibit neuraminidase, that is essential for viral replication and release.
Zanamivir:
- Oral/inhalation route and is approved for 7yrs and above.
- Absence of significant metabolism
- Rapid renal clearance
- Nasal & throat discomfort
- Bronchospasm in patients with reactive airway disease
Oseltamivir:
- Given orally and approved for one yr and above.
- Prodrug activated in gut and liver
- t ½ – 6 – 10 hrs
- Excreted in urine
Adverse Effects:
Nausea and vomiting which decreases by administration with food.
Ribavirin
- Synthetic guanosine analog.
- Effective against a broad spectrum of RNA & DNA viruses.
- Orally, I/V, as an aerosol
- Drug & metabolites excreted in urine.
Mechanism of Action:
- Ribavirin inhibits viral mRNA by converting into ribavirin triphosphate (RTP).
- Ribavirin triphophate inhibits replication of wide range of DNA, RNA viruses, including influenza A and B, Parainfluenza respiratory syncitial and Paramyxovirurs, HCV and HIV
Therapeutic Uses
- Respiratory syncytial viral pneumonia and broncholitis.
- Aerosolized ribavirin used to treat influenza A & B infection.
- I/V Ribavirin decreases mortality in lassa fever & haemorrhagic fever if started.
- Severe measles pneumonitis.
Adverse Effects
- Dose dependent Anemia.
- Increased bilirubin levels
- Aerosolized ribavirin cause conjunctival or bronchial irritation.