Antiviral Drugs Flashcards
What are the three different types of influenza and how do they differ?
Influenza A: Multiple host species, capable of antigenic drift and shift. Responsible for many pandemics and considerable mortality.
Influenza B: Human only, lower mortality.
Influenza C: Common cold like symptoms.
What are the common complications of influenza infections?
Bronchitis/Pneumonia
Sinusitis
Exacerbation of underlying disease.
What are the two virulence factors on the surface of the influenze virus?
Haemaglutinin - this adheres to sialic acid on human respiratory epithelium.
Neuraminidase - cleaves sialic acid groups allowing replicated viruses to be released from the hijacked cell.
What does the influenza vaccine contain?
The non-live influenza vaccine includes either inactivated (injectable) or weakened/attenuated (nasal spray) flu viruses. Which viruses are chosen are based on a WHO list published for that year.
What is AMANTADINE?
This is a drug that blocks the M2 channel of the influenza virus and thus prevents the ‘uncoating’ and thus replication of the virus within the cells.
Which strain of influenza is AMANTADINE active against?
Influenza A only.
What is a major issue with AMANTADINE as a treatment for influenza?
It only takes a single point mutation for resistance to emerge and then this can be transmitted. More and more of the pandemic causing isolates are resistant to M2 channel blockers nowadays.
Why do viral neuraminidases make good target sites for anti-influenza drugs?
The active site of the viral neuraminidase, because it has a specific job to do (cleaving sialic acid domains) is not as variable as the rest of the viral proteins and so is conserved across both A and B strains, even those that are resistant to Amantadine therapy.
If we give a viral neuraminidase inhibitor, how does this affect the replication of the virus?
The influenza viruses can be made but cannot be released as the blocked neuraminidase cannot cleave the sialic acid - haemaglutinin linkage and be released. ‘Daughter’ viruses therefore build up at the surface of the cell that was invaded. These are not free to go on and invade other cells.
Why is Zanamivir given by dry powder aerosol only?
It is degraded by acid and thus would have such a low oral bioavailability that it is useless to package it as a tablet.
Describe the metabolic characteristics of Oseltamivir.
It is a prodrug that is modified (active site changes shape) once in the body. It has an 80% bioavailability which is considered good.
What exactly do the neuraminidase inhibitors do to the course of the influenza case?
They shorten it but effects are only significant if it is given soon after the onset of symptoms.
Do viral neuraminidase inhibitors have any effect on mortality.
A study in Canada found that they did decrease mortality but the confidence interval was too big (just) for us to say that they have a statistically significant impact on mortality.
Where else can Oseltamivir be used?
It has been shown to have a significant effect in reducing risk of contracting influenza in vulnerable groups.
What are some side effects of Oseltamivir?
- Abdominal Pain
- Vomiting
- Epistaxis
