__________ is an inorganic pyrophosphate that inhibits all HSV and HIV.
Foscarnet
Foscarnet is effective against _____ _____ CMV and _____ _____ HSV and VZV strains.
ganciclovir-resistant, acyclovir-resistant
What is foscarnet's MOA?
It reversibly blocks the pyrophosphate binding site of viral polymerase non-competitively. This inhibits cleavage of pyrophosphate from dNTP's.
Resistance to foscarnet occurs through _____ _____ in the viral polymerase gene.
point mutations
Foscarnet use can cause chronic __________. This leads to significant CNS disturbances like tremors and seizures.
hypocalcemia
Which of the following is not an indication for foscarnet?
A. Ganciclovir-resistant CMV retinitis
B. Acyclovir-resistant HSV infections
C. Zidovudine-resistant HIV
D. Prophylaxis for bone marrow transplants
C
__________ is an acyclic guanine nucleoside, similiar to acyclovir.
Ganciclovir
What is ganciclovir's prodrug form?
Valganciclovir-L-valyl ester
What infection is ganciclovir particularly effective against?
CMV
During HSV infection ganciclovir is initially phosphorylated by virally encoded _____ _____. A viral__________ phosphorylates it during CMV infection.
thymidine kinase, phosphotransferase
The di- and triphosphate forms of ganciclovir are phosphorylated by _____ _____.
cellular enzymes
The triphosphate form of ganciclovir is a competitive inhibitor for _____ at the viral DNA polymerase.
dGTP
What happens when ganciclovir is incorporated into viral DNA?
It halts elongation.
How does viral resistance develop to ganciclovir?
Decreased phosphorylation due to mutations in the viral phosphotransferase gene and mutations in the viral DNA polymerase gene.
T/F Ganciclovir is more effective in acyclovir-resistant HSV.
What is the primary dose-limiting ADR for ganciclovir?
Myelosuppression- neutropenia and thrombocytopenia
How does one treat ganciclovir-induced neutropenia?
A recombinant granulocyte colony stimulating factor.
Ganciclovir is used to treat CMV infections particularly in _____ _____.
immunosuppressed patients
Which drug is only available as a DMSO formulation for topical treatment of herpes labialis, genitalis, and zoster?
Idoxuridine
What fluorinated nucleoside has limited use in the USA in treating keratoconjunctivitis?
trifluridine
The hepatitis B virus has dsDNA, but works through an RNA intermediate with _____ _____.
Reverse transcriptase
_____ _____ & _____ are general types of agents that treat HBV and HCV infections.
Nucleotide analogs, interferons
_____ is an acyclic phosphate nucleotide analogue of adenosine monophosphate.
Adefovir
What is the diester prodrug of adefovir?
Adefovir dipivoxil
The __________ of adefovir is a competitive inhibitor at viral _____ _____ and _____ _____ for dATP.
DNA polymerase, reverse transcriptase
If adefovir is incorporated into the viral DNA, it acts as a _____ _____.
Chain terminator
What is the most notable ADR with adefovir dipivoxil use?
Nephrotoxicity and tubular dysfunction
Other than chronic HBV infection, adefovir is effective in treating _____ _____ HBV infections.
lamivudine-resistant
__________ are non-glycosylated, recombinant proteins that inhibit animal viruses.
Interferons
Interferon binding to its receptor activates which pathway leading to expression of proteins influencing viral replication?
JAK/STAT
Describe the several effects of interferon therapy.
Transcription inhibition, translation inhibition, protein processing inhibition, and virus maturation inhibition
T/F Interferons must be given IV.
False, IM or Sub-Q
__________ increases blood levels and duration of interferons.
Pegylation
Injection of interferons can cause an _____ _____ syndrome with fever, chills, headache, and myalgia.
influenza-like
T/F Interferon therapy clears HCV infections better than HBV infections when used as monotherapy.
False, 1/3 of HBV patients see viral load clearance, but HCV is generally not cleared.
Lamivudine inhibits HBV _____ _____, leading to _____ _____.
DNA polymerase, chain termination
Lamivudine is commonly used with _____ or _____ to treat hepadnaviruses.
Adefovir, penciclovir
_____ is a purine nucleoside analog that inhibits a wide variety of DNA and RNA viruses.
Ribavirin
What is ribavirin's MOA?
Generally unclear, but it seems to alter intracellular nucleotide pools with inhibition of viral mRNA synthesis. It also inhibits GTP-dependent 5' capping of mRNA.
Ribavirin is indicated for _____ infections.
HCV
Ribavirin is administered with ___________ for standard treatment of _____.
