Antivirals Flashcards
Name features of Influenza A?
Main seasonal outbreak
Multiple host species
Antigenic drift and shift
what are common complications of Influenza ?
Bronchitis, pneumonia
– Sinusitis
– Exacerbation of underlying disease
what are features of Influenza B?
Only in humans
what are the structures of Influenza A ?
RNA Protein envelope Lipid envelope M2 and M1 Proteins on outside : Neuraminidase and Hemaggltuinin
what can Hemagglutinin do?
recognise human respiratory cells to stick to surface - salic acid , URT
what does the M2 ion channel do ?
once the virus enters the host cell this cannel allows H+ ion to enter to break uo the virus particle to replicate it self
how do Amantadine and Rimantadine work ? what do they work on ?
what else do they work on ?
Antivirals that work in Influnza A
Block M2 ion channels = inhibit viral uncoating
Parkinson’s
what are side effects of amantidine ?
CNS and renal
how was resistance developed for Amantadine ?
single point mutation in M2 gene which is transmissible
the shape of channel changes so drug does not bind into the channel
what does Neuraminidase do ?
Breaks the Sialic acid and Heamagglutinin bond and allows a budding virus particle to break off
what is the pharmokinetics of Zanamavir ?
Low bioavail - dry aersol needed
Acid degrades it
long half life
renally excreted
what is an advantage of Oesltamivir ?
Pro-drug with high bio avail so in tablet form
how does Oesltamivir and Zanamavir work?
competitively inhibits the NA enzymes so virus aggregation occurs and stays in the cell
what is a goal when starting Zanamavir and oesltamivir ? what can it lead to ?
start treatment early when symptoms start
severity and duration decreases , reduction in mortality
what is a major use of Osetltamvir ?
seasonal prophylaxis
what side effects of Zanamavir ?
vomiting
abdo pain
epistaxis
low side effect profile
what is the proper name for Bird flu ?
H5N1 infection
how do we reduce resistance globally ?
survelliance -
WHO system
NA inhibitor Susceptibility network
how do virus’ develop resistance to NA inhibitors ?
Change in shape of enzyme
what strain develop resistance in Oseltamivir ?
H1N1 (human strain) - not triggered by over use of antivirals
why is Oseltamivir now still in use ?
circulating H1N1 human is replaced by swine H1N1 which is susceptible to it
what are primary care guidlines in flu outbreaks?
Healthy people: no Rx unless pt felt to be at risk
– At risk (inc preg): oseltamivir asap (no need for confirmation)
– Severely immunosuppressed: oseltamivir or inhaled zanamivir
(esp if H1N1)
what are secondary care guildlines in flu ?
if suspected give Oseltamivir asap
if H1N1 is high try Zanamivir
what is EBV associated with?
non-malignant and malignant
lymphomas
what is general structure of HSV and VZV ?
large double-stranded DNA genome
covered by a capsid and lipid bilayer envelope.
how do HSV enter cells ?
via MHC class molecules
how does shingles present ?
what kind of patients will you see it in ?
reactivation of the virus (Herpes zoster) which lies dormant in a dorsal root
ganglion after primary chickenpox infection.
elderly and immunocompromised
What is the main treatment principle of Shingles?
start antivirals within 72 hours
what is the main clincinal differences of HSV 1 and 2 ?
1= genital or oral ulceration 2 = Just genital
what is treatment of HSV?
Oral aciclovir or valaciclovir are administered for 7-10 days to treat the multiple
painful genital herpes lesions
What is common complication of HSV?
recurrent lesions to occur from reactivation of latent
virus in the dorsal root ganglia. Symptoms are usually less severe than the primary episode.
How does Acyclovir and Valaciclovir work ?
nucleoside inhibitors of viral DNA replication
how does Aciclovir work ? why is it good for humans
guanosine analogue active against many DNA viruses by inhibiting synthesis of viral DNA. Initial activity
relies on phosphorylation by a viral protein (thymidine kinase) limiting their initial human cell toxicity
how does resistance to Aciclovir develop?
change in thymidine kinase- prevalent in immunocompromised
what are side effects of Aciclovir ?
what D-D interaction ocurs?
N+V
Photo sensitivity
antibiotics could = Nephrotoxicity
what is PK of aciclovir ?
It is well distributed and most is eliminated by the kidneys with a half-life of around 3 hours