8.14_Antivirals Flashcards
(23 cards)
Targets of antivirals
penetration, uncoating, genome replication, RNA synthesis, protein synthesis, re-assembly, release from host
Common Herpes Rash
presents with a vesicular rash on an erthematous base
Acyclovir
treats HSV-1 and 2 well, is also drug of choice for VZV, is an analogue of deoxyguanosine and will be incorporated into genome as replication occurs therefore ending the replication,
it is activated in a cell with virus by a viral thymidine kinase that phosphorylates it, this is what makes it specific to viral cells
It also has greater affinity for viral polymerase
What is more toxic antibiotics or antivirals?
Antivirals are more toxic because virals use so much of host cell machinery that it is hard to differentiate or be specific in attack
Valacyclovir and Famciclovir
These are two modifications of acyclovir and are used for oral therapy. They have modification that makes them have a much higher bioavailability and be better absorbed in GI tract, these are considered a prodrug while acyclovir is not
Often used for prophylaxis and treatment but severe infections need acyclovir too
How to treat latent herpes viruses?
These cannot be treated with acyclovir or the others because there is nothing replicating. Latency means the virus is hanging out in a nerve cell and not doing anything so antivirals have no effect, must wait until prodromal phase reappears
Ganciclovir
Similar to ancyclovir, but phosphorylated by a cellular kinase so it is less specific. used in treatment of cytamegalovirus, also has a pro drug called valganciclovir
Resistance to Herpes virus Antivirals
Can occur due to mutations in the viral thymine kinase or the viral polymerase, but in regular immuno patients it is uncommon,
Adamantanes
group of antiinfluenze drugs, this group inhibits the M2 protein that is in charge of uncoating the virus when it enters a host, these are good for flu A but not flu B
Adamantanes examples
Amantadine and Rimantadine are both examples of an adamantane, they target the M2 and prevent uncoating and release of virus in a cell
Neuraminidase inhibitors
class of anti influenzas that target the enzyme neuraminidase which helps cleave the virus from the cyalic linkage to the host when it is trying to leave, so if inhibited you will get a collection of viruses attached to outside of host
Target flu A and B
Neuraminidase examples
Oseltamivir and Zanamivir Peramivir and Laninamivir
Resistance to Neuraminidases and side effects
very easy for cells to make new neuraminidases so they drugs do not work anymore, side effects often include some neuropsych issues
These also dont provide a great reduction in duration of disease only about 1.3 days and fever also down for only about 1 day
Ribavirin
Nucleoside analogue with antiviral activity, used to treat infants with RSV through aerosol treatment, can also treat some funky things like lassa fever, side effect is anemia
What does a retrovirus need to bring into a host?
A reverse transcriptase to make the DNA intermediate
A viral polymerase to transcribe
Classes of antiretroviral agents
Nucleoside reverse transcriptase inhibitors
Nucleotide RT inhibitors
Non nucleotide RT inhibitors
Protease inhibitors
Fusion/entry inhibitors
Integrase inhibitors-inhibits DNA from being inserted into host
Challenges of HIV therapy
successful therapy for decades with minimal toxicity
eradication or functional cure
effective prevention of HIV from mother to child and sexually spread
Vaccine?
PEP versus PrEP
Post-Exposure prophylaxis is when you start treatment right after likely infected
Pre Exposure prophylaxis is when you start when you think there is a high risk of infection but not sure if infected
Resistance to antiretrovirals
has a wild polymerase that leads to lots of resistance through high mutation rates
to combat we hope patients ahere to medication guidelines and can genotype the viral gene and also watch phenotype or how virus functions
What type of therapy is best for HIV
This is measured with CD4 counts and plasma levels of HIV1RNA
Highly Active Antiretroviral Therapy HART is best
Monotherapy CD4 and HIVRNA info
CD4 will rise and HIV RNA decreases but converges back in middle showing resistance
Double RTI Therapy CD4 and HIV RNA info
CD4 rises and HIV RNA decreases and they start to come back together but do not completely converge, so some better than monotherapy
HART or Highly active Antiretroviral Therapy CD4 and HIVRNA
CD4 continuously increases and HIVRNA decreases, they do not show any signs of converging, so best therapy
Even have combination drugs that can be given once daily now so less toxic and easier adherence
