Term
agents that disrupt virus attachment to host cell receptors, penetration, or uncoating
agents that inhibit virus-associated enzymes (DNA polymerases, neuraminidase)
agents that inhibit viral transcription/translation
agents that interfere with viral regulatory proteins
agents that interfere with glycosylation, phosphorylation, sulfation
agents that interfere with the assembly of viral proteins
agents that prohibit the release of viruses from cell surface membranes |
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Definition
| potential drug targets for antivirals |
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Term
idoxuridine (pyrimadine derivative with a sugar group)
trifluridine (pyrimadine derivative with a sugar group)
vidarabine (purine derivative with a sugar group)
Acyclovir (purine derivative)
valacyclovir (produg of acyclovir)
ganciclovir (purine derivative)
penciclovir (purine derivative)
famciclovir (purine derivative)
cidofovir (pyrimadine derivative, phorphorylated)
foscarnet (inorganic phosphate group)
[image] |
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Definition
| antivirals for herpes virus infection |
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Term
[image] [image]
pyrimiDINE analog (idoxuriDINE)
halogen characteristics
low selective toxicity (better in eye infections)
incoporation of idoxuridine instead of thymidine into viral DNA
DNA susceptible to strand breakage
mutation rate increased
errors in subsequent RNA and protein synthesis
anti HSV agent
ADRs: local allergic reactions |
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Definition
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Term
[image]
pyrimiDINE analog (trifluriDINE)
CF3 similar in size to CH3
incorporated into viral (and host cell) DNA
short half life
less toxic than idoxuridine
anti HSV agent
ADR: burning sensation |
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Definition
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Term
[image]
purine derivative
vidarabine biochemical reactions: phosphorylation to VIDARABINE TRIPHOSPHATE, deamination to hypoxanthing arabinioside
potent inhibitor of ribonucleotides reductases and DNA polymerases -> interferes with viral nucleic acid replication
competitive inhibition of the HSV DNA polymerase
selective toxicity
anti HSV agent |
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Definition
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Term
[image]
highly selective inhibitor of HSV replication
activated to acyclovir monophosphate by herpes virus specific thymidine kinase -> faster in infected cells (replicated more quickly)
then is converted to di and triphosphate by guanosine monophosphate enzyme (cell enzyme)
viral DNA polymerase inhibited competitively by acyclovir triphosphate
preferential uptake of acyclovir by infected cells
anti HSV agent |
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Definition
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Term
| mutation in thymidine kinase gene (HSV enzyme that activates acyclovir to the monophosphate) |
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Definition
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Term
PRODRUG of acylclovir
after absorption full conversion to acyclovir (1st pass metabolism)
competitively inhibits viral DNA polymerase
anti HSV agent |
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Definition
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Term
poorly absorbed from GI tract, given IV
metabolism: very little
excretion: kidney |
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Definition
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Term
well tolerated
topical may cause burning in genital lesions
IV: phelbitis, local reactions, renal toxicity
bone marrow toxicities at higher doses
renal toxicity: due to precipitation in renal tubules
drug interactions: cimetidine and probenecid decrease renal clearance and increase plasma concentrations |
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Definition
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Term
[image]
acyclic guanine mucleoside analog (famciclovir is the diacetyl ester prodrug)
inhibitor of viral DNA synthesis -> affinities for viral DNA polymerase
acceleration of cutaneous healing and pain - reduces duration of shedding and time to healing
effective in immunocompetent patients
IV and topical administration
well tolerated drugs
anti HSV agent |
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Definition
| MOA of penciclovir and famciclovir |
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Term
mutations to thymidine kinase (HSV specific enzyme that leads to the monophosphate of the drug)
cross resistance with acyclovir |
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Definition
| resistance to penciclovir and famciclovir |
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Term
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acyclic nucleoside analog of guanosine
converted to the monophosphate and triphosphate
inhibits viral DNA polymerase
inhibition of the incorporation of the deaxyguanosine triphosphate into enlongating viral DNA
not an absolute terminator of the synthesis
anti HSV agent |
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Definition
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Term
mutations that reduce the conversion to monophosphate
mutations in viral DNA polymerase |
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Definition
| resistance to ganciclovir |
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Term
poor oral bioavailability, given IV
penetrates BBB
eliminated renally |
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Definition
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Term
narrow therapeutic index
granulocytopenia, thrombocytopenia, azoospermia, rise in SrCr
CNS: from HA to behavioral changes to convulsions to coma
infusion related phelbitis, azotemia, rash, fever, LFT abnormalities
drug interactions: drugs toxic to the bone marrow and drugs that cause nephrotoxicity |
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Definition
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Term
foscarnet
ribavirin
interferon |
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Definition
| broad spectrum antiviral agents: active against a wide variety of DNA and RNA viruses |
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Term
[image]
inorganic pyrophosphate
broad spectrum antiviral: HSV, HIV, CMV, VZV
selective inhibition of DNA polymerases
inhibition of the reverse transcriptase
non-competitive inhibition: direct interaction - blocks binding of pyrophosphate to the pyrophosphate binding site, prevents elongation
additive and synergistic effects |
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Definition
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Term
| mutations in DNA polymerase |
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Definition
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Term
poorly absorbed, administered IV
intra and inter patient variability
not metabolized
renally eliminated |
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Definition
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Term
dose limiting ADRs: renal impairment, acute infusion-related symptoms, disturbance in serum Ca and phosphate levels
nephrotoxicity
diarrhea and vomiting
metabolic abnormalities (bind to free, ionized plasma Ca) - electrolytes should be monitored |
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Definition
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Term
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antihepatitis antiviral
low incidence of resistance b/c the drug is already phosphorylated (don't need viral kinase enzyme)
competitive inhibitor of DNA polymerase and reverse transcriptase
PRODRUG is absorbed rapidly and hydrolyzed by esterases |
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Definition
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Term
eliminated unchanged by renal excretion
dose related nephrotoxicity and tubular dysfunction
HA, abdominal discomfort, diarrhea
drug interactions |
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Definition
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Term
adefovir
lamivudine
entecavir
telbivudine
LATE |
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Definition
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Term
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nucleoside analog
antihepatitis agent
inhibits HIV reverse transcriptase and DNA polymerase |
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Definition
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Term
mutations in DNA polymerase
lamivudine-resistant strains are sensitive to adefovir and entacavir |
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Definition
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Term
well absorbed PO
excreted in the urine
inactive metabolite
ADRs: well tolerated |
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Definition
| ADME and ADRs of lamivudine |
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Term
[image]
synthetic guanosine analog
broad spectrum: DNA and RNA viruses, herpes viruses are the most sensitive, influenza A and B are very sensitive
clinical attention to treatment of HIV and hepatitis
MOA is controversial
inhibits synthesis of RNA/DNA
undergoes intracellular phosphorilation (host enzyme)
monophosphate: competitive inhibitor of cellular IMP dehydrogenase - interferes with GTP synthesis (needed for the virus to grow)
triphosphate: also inhibits GTP-dependent 5' capping of viral mRNA (stops last part of mRNA synthesis) |
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Definition
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Term
rapidly absorbed PO
also available IV
also an aerosol administration
metabolized by the liver
renal excretion |
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Definition
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Term
well tolerated
related to dose duration
mild conjuctive irritation
rash
from aerosol administration: transient wheezing, reversible deterioration of pulmonary function |
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Definition
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