antiviral pharmacology/medchem Flashcards
immune globulin use
acute, serious infections
post exposure prophylaxis
used with nucleoside antiviral
herpes genome
dsDNA
influenza genome
(-) ssRNA
viruses that use host polymerase
DNA viruses herpes (human and simplex) varicella epstein-barr CMV
acyclovir MoA
guanosine analog prodrug
terminates DNA chain synthesis
what converts acyclovir to active drug
- viral thymidine kinase does first phosphorylation
- guanosine monophosphate kinase does rest
resistance mechanisms to acyclovir and valacyclovir
- deficient thymidine kinase
- altered thymidine kinase
- altered DNA polymerase
gancyclovir activity against
CMV
HSV
VZV
HHV
ganciclovir toxicity
high because its less specific to viral thymidine kinase
-potential for bone marrow toxicity
famciclovir features
- prodrug of penciclovir which increases bioavailability
- similar to acyclovir but longer duration
cidofovir MoA
cytosine analog that inhibits DNA synthesis
No viral TK needed
cidofovir dose limiting toxicity
nephrotoxicity
cidofovir route
IV only due to poor bioavailability
foscarnet MoA
inhibits DNA polymerase by blocking nucleotide binding, with no need of triphosphate (thus TK) like acyclovir and others
foscarnet side effects
headache tremor seizures hallucinations *all due to chelation of calcium*
foscarnet dose limiting toxicity
nephrotoxicity
hypocalcemia
foscarnet route
IV only
idoxuridine and trifluridine (thymidine analogs) MoA
is phosphorylated then inhibits DNA synthesis by inhibiting thymidylic phosphorylase
fomivirsen use
CMV retinitis
fomivirsen MoA
inhibits replication through specific and nonspecific mechanisms like virus binding
fomivirsen route
eye injection (intravitreal)
docosanol use
cold sores
imiquimod use
HPV infections
imiquimod MoA
not fully understood, does induce secretion of pro-inflammatory cytokines
influenza strain that causes pandemics
A only
influenza nomenclature
H (hemagglutinin - 16 subtypes)
N (neuraminidase - 9 subtypes)
neuraminidase inhibitor drugs
zanamivir
oseltamivir (prodrug)
neuraminidase inhibitor MoA
inhibits cleavage of sialic acid and the release of virus from the infected cell
neuraminidase inhibitor adverse effects
bronchospasm
unusual psychiatric behavior
d/n
Uncommon though
viral uncoating inhibitor use
influenza A
viral uncoating inhibitor drugs
amantadine
rimantadine
viral uncoating inhibitor MoA
inhibits M2 ion channel in flu virus and uncoating of virus in endosome
viral uncoating inhibitors adverse effects
GI and CNS
hepatitis C genome
(+) ssRNA
hepatitis B genome
dsDNA-RT
hepatitis strain with no vaccine
C
hep A transmission
fecal-oral
hep C transmission
injection drug use
blood exposure
interferon use
in combination with ribavirin for hep C
not very useful however
ribavirin use
combo therapy for hep C
ribavirin MoA
- inhibits capping of 5’ end of mRNA
- inhibits inosine monophosphate deyhdrogenase in DNA production
ribavirin adverse effects
- hemolytic anemia
- bone marrow suppression
- possibly teratogenic
NS5A inhibitor MoA
inhibits the scaffolding protein that allows for the building of complex protein structures for use in the hep C virus
NS5A (replication complex) inhibitor drugs
daclatasvir velpastasvir pibrentasvir elbasvir ledipasvir
NS5A inhibitor adverse effects
headache
fatigue
nausea
HCV protease (NS3/A4) inhibitor drugs
glecaprevir
paritaprevir
grazoprevir
HCV protease inhibitor adverse effects
anemia
skin rashes
HCV polymerase (NS5B) inhibitors
sofosbuvir
HCV polymerase inhibitor drug interaction
serious bradycardia with amiodarone
hep B transmission
contact with blood or body fluids of infected person
unique DNA construct for hep B
covalently closed circular DNA (cccDNA)
HIV drugs used for hepatitis (NI inhibitors)
tenofovir
entecavir
valacyclovir features
- great oral bioavailability
- cleaved to active drug by valacyclovirase before portal circulation
idoxuridine and trifluridine toxicity
bone marrow toxicity
-not very specific for virus so we get a lot into our DNA
which drugs have the phosphonate group
cytidine analogs
cidofovir
deoxycytidine
why aren’t adamantanse used much
near universal resistance
hemagglutinin
influenza component that binds to human glycoprotein containing sialic acid
NI inhibitors MoA
- compete with adenosine to cause chain termination
- prodrug
HCV polymerase inhibitor (NS5B) MoA
inhibit nucleoside biosynthesis and mRNA capping
HCV protease inhibitors MoA
bind non-covalently to serine in the active site
