EXAM 4 antivirals 1 HSV, VZV, CMV, FLU Flashcards
Herpes simplex viruses 1 (HSV1)
oral herpes
diagnosis via swab and PCR testing
Herpes simplex viruses 2 (HSV2)
Genital mucosa
Commonly causes genital herpes
Infection within sacral ganglia
HSV1 + HSV2
central nervous system
HSV encephalitis is mostly caused by HSV1
Can see changes on imaging
anti-herpes agents
Acyclovir
Valacyclovir
Famciclovir (not used in practice)
Penciclovir
acyclovir MOA
Prodrug that gets requires 3 step phosphorylation
Virus produces enzyme that causes selective phosphorylation
competitive inhibitor of viral DNA polymerase and competes with dGTP (guanine).
Acts as a chain terminator and inhibits DNA synthesis
acyclovir spectrum
active against HSV-1, HSV-2, and VZV
acyclovir resistance
Two mechanisms: mutations in thymidine kinase and DNA polymerase
More likely to occur in immunocompromised people
acyclovir adverse effects
Nephrotoxicity: more likely to occur with IV admin
Give w/ IV fluids to prevent
but generally well tolerated
valacyclovir
L-valyl ester of acyclovir and is converted to acyclovir by esterase in intestine and liver
improved efficacy compared to acyclovir (increased oral bioavailability)
SAME ADRs, MOA, and spectrum as acyclovir
famciclovir and penciclovir MOA
competitive inhibitor of viral DNA polymerase
Does not cause immediate chain termination
Obligate DNA chain terminator (incorporate into DNA)
famciclovir and penciclovir resistance
Viral kinase mutants: confer cross-resistance to penciclovir and acyclovir
famciclovir vs penciclovir
famiclovir is a prodrug of penciclovir
famciclovir is converted by first pass metabolism in intestine and liver
penciclovir vs acyclovir
higher affinity for HSV TK than acyclovir because it is more stable
HSV DNA polymerase have higher affinity for acyclovir triphosphate than penciclovir triphosphate
Varicella Zoster virus
DNA virus that cases infections referred to chickenpox or shingles
Varicella (chicken pox)
Zoster (shingles)
Varicella Zoster virus treatment
acyclovir
valacyclovir
oral for varicella or zoster
IV for disseminated zoster
famciclovir
used to treat zoster
Cytomegalovirus
Severe infection can occur if during fetal development or in immunocompromised patients
Cytomegalovirus drug therapy
ganciclovir
valganciclovir
ganciclovir and valganciclovir MOA
same as penciclovir
competitive inhibitor of viral DNA polymerase
Does not cause immediate chain termination
Obligate DNA chain terminator (incorporate into DNA)
ganciclovir vs acyclovir
better substrate for CMV than acyclovir
ganciclovir ADRS
bone marrow suppression
main side effect –> dose limiting
ganciclovir resistance
due to mutations in CMV kinase (UL97) or CMV DNA pol (UL54)
mutations in kinase are not cross-resistant to cidofovir or foscarnet
mutations in DNA pol may be cross-resistant to cidofovir or foscarnet
valganciclovir
Monovalyl ester of ganciclovir (increases oral bioavailability 60%)
Rapidly hydrolyzed to ganciclovir
Uses: treat CMV retinitis
foscarnet MOA
inhibits viral DNA polymerase
Does not require phosphorylation for activity
Carboxyl overlaps with binding site of phosphonates and traps polymerase in closed formation
foscarnet spectrum
CMV retinitis
foscarnet resistance
mutations in DNA pol or HIV RT
Resistant CMV isolates are cross resistant to ganciclovir
Foscarnet is usually still effective against cidofovir resistant CMV
Cidofovir MOA
competitive inhibitor and chain terminator
Does not require activation by viral kinases
Cidofovir spectrum
CMV
HSV1/2
VZV
adenovirus
poxvirus
polymavirus
HPV
Letermovir MOA
inhibits terminase complex (responsible for cutting out genomes during DNA replication process): pUL56/89/51
Result: inhibition of CMV replication and prevention of CMV infection
letermovir drug interactions
CYP3A4 inhibitor, substrate/inhibitor of OATP1B1/3
life cycle of influenza virus
Virus is sysnthesized within the cell which undergoes mRNA synthesis and RNA replication
The mature cell is connected to the outside of the host cell
Neuraminidase cleaves this connection (glycolytic bonds) and frees the virus cell
This facilitates virus dissemination: hemataglutin binds to terminal sialic acid residues
target for influenza virus
Neuraminidase: is the main target
Neuraminidase inhibitors block this cleavage
Essential for virus replication
drugs to treat influenza virus
oseltamivir
zanamivir
permivir
baloxavir marboxil
oseltamivir and zanamivir MOA
Prodrug converted to active form by liver
Metabolite is an effective inhibitor of NA
oseltamivir and zanamivir spectrum
active against influenza A and B
oseltamivir and zanamivir resistance
mutations in active site of neuraminidase
There is flu A virus with reduced susceptibility to oseltamivir
Drug resistant virus occurs in 3% of patients receiving oseltamivir
More resistance against oseltamivir compared to zanamivir
peramivir MOA
Parental NA inhibitor
peramivir spectrum
effective against influenza A and B
peramivir resistance
mutation in active site of neuraminidase
Baloxavir marboxil MOA
inhibits viral “cap-snatching” –> blocks transcription
Binds to PB2 subunit of RNA pol and inhibits cap-dependent endonuclease
Baloxavir marboxil spectrum
flu within first 48 hrs of symptoms
