MD 3

What are the two types of influenza outbreaks

seaosnal - most common usually comprises a variant of a previous strain (predictable)

pandemic/epidemic - usually a new strain posisbly of non-human origin (unpredictable)

what is antigenic shift

genetic reassortment - entire genes encoding a different H or N sub-types is incorporated into the new viruis

often occurs in animal hosts which are co-infected with two or more strains

result - you get a completely new viruis subtype

what are 3 keys points about pandemic influenza?

no immune history so no natural protection

highly pathogenic and result in high rates of mortaility

often non distinction between ‘at risk’ groups and healthy adults

what are two examples of Adamantanes (M2 inhibitors)

amantadine

rimantadine (suffers from same problems of amantadine just less toxic)

two examples of Neuraminidase inhibitors

oseltamivir

zanamivir

how do Adamantanes (M2 Inhibitors) work?

block M2 transmembrane protein of influenza A proteins - decreases the release of influenza A viruis particles into host cell

uses of amantadine

adults and children 1 and over

reduce duration of illness of about 1 day when administered within 48hrs of onset of illness

orally administered

problems with Amantadine

rapid development of resistance

wider range of side effects and toxicity

what do Neuraminidase inhibitors do

competitive inhibitors that compete with the natural receptros for access to the neuraminidase active site - active aganist all strains of influenxa (A,B,C)

3 key points about Zanamivir

approved for treatment of influenza A & B among those 7 and over

reduces duration of illness by one day if administered within 48hrs of onset of symptoms

inhalation delivery of dry powdered drug in a lactose carrier

what 4 modifications were made to Oseltamivir to improve oral BA

1. hydrocarbon side chain added - improves lipophillicity

2. removed Guanidino - reduced polarity

3. converted carboxylic acid to ester - improves lipophillicity

4. removed ring oxygen - improved stability

4 key points about oseltamivir

orally adminsitered tablets and syrup for children

approved for treamtnet and prophylaxis of influenza A and B

absorption of pro-drug is high

reduces duration of illness by one day if administered within 48 hours of onset of symptoms

management of seaosnal influenza

vaccines first line of defense

management of influenza pandemic

NA inhibitors are first line of defense

adminsitered more widely for prophylaxis in an errfot to reduce spread of infection