4/25 Antivirals Flashcards
name 2 neuraminidase inhibitors
Oseltamivir
Zanamivir
MoA of Oseltamivir or Zanamivir
Inhibits influenza neuraminidase -> decrease release of virus
difference between Oseltamivir or Zanamivir?
Oseltamivir – oral drug
Zanamivir – inhaler; limited use in young children or patients who are unable to follow instructions
indications for Oseltamivir or Zanamivir?
influenza A/B (trmt/prevention)
name nucleotide analogs (at least 5)
Ribavirin Acyclovir Famciclovir Valacyclovir Ganciclovir Valganciclovir
MoA of Ribavirin?
nucleotide analog that inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase (prevents ribosomes from binding to viral RNA)
half-life of Ribavirin?
long half-life (stored in RBC and released over days)
Indications for Ribavirin?
RSV
HepC (chronic)
ADRs of using ribarivin?
Hemolytic anemia
Teratogen
Gout
What are 2 alternate drugs that are within the same class as acyclovir?
Famciclovir
Valacyclovir (pro-drug)
MoA of Acyclovir?
Guanosine analog; phosphorylated by HSV/VZV–TK and subsequently phosphorylated by host enzymes to form a triphosphate
preferentially inhibits viral DNA polymerase chain termination (virus must be actively replicating; NO effect on latent forms)
Why should you be be considered when you prescribe acyclovir?
does the patient have renal failure?
renally excreted, therefore dose must be adjusted for patients with renal insufficiency
compare oral bioavailability between acyclovir and the 2 alternate drugs that are within the same class
acyclovir: not great
valacyclovir: oral pro-drug of acyclovir; better oral bioavailability
famciclovir: best oral bioavailability
Indications for acyclovir? valacyclovir?
HSV (mucocutaneous and genital lesions, encephalitis, pregnant women/neonatal, prophylaxis in immunocompromised patients) = oral acyclovir or valacyclovir
VZV (healthy, immunocompromised, pregnant women/neonates) = valacyclovir*, acyclovir
VZV, uncomplicated = famciclovir
CMV – weak activity
when would you normally prescribe famciclovir?
VZV (according to first AID)
Mechanism of resistance for Acyclovir et al?
Mutated viral TK
common among immunodeficient patients, eg AIDs patients, who receive ACV for prolonged periods
Side effect of Acyclovir et al?
What can you do to prevent this?
Nephropathy due to obstructive crystalline formation; can progress to acute renal failure if not adequately hydrated
CNS disturbances
What is an alternate drug that is within the same class as Ganciclovir?
Valganciclovir
What is the mxn of ganciclovir?
Guanosine analog that is converted to 5MP by CMV viral kinase and subsequently phosphorylated by host enzymes to form a triphosphate
preferentially inhibits viral DNA polymerase
why is ganciclovir more toxic than acyclovir?
more toxic to host enzymes than acyclovir because it can actually be incorporated into DNA, thereby inhibiting HOST kinases and DNA polymerases
What is valganciclovir?
valganciclovir is a pro-drug of ganciclovir; better oral bioavailability
Indications for ganciclovir?
CMV*
HSV
EBV
mechanism of resistance for ganciclovir?
UL97 mutated CMV DNA polymerase or lack of viral kinase
side effects of ganciclovir?
Bone marrow suppression - Leukopenia - Neutropenia - Thrombocytopenia Renal toxicity Teratogen
What is Foscarnet?
Pyro”fos”phate inhibitor that binds to the pyrophosphate-binding site of DNA polymerase; does not require activation by viral kinase
Indication for Foscarnet?
Ganciclovir-resistant CMV retinitis
Acyclovir-resistant HSV
Mxn of resistance for Foscarnet
mutated DNA polymerase
ADR for foscarnet?
Nephrotoxicity
Sequesters divalent cations –> Hypo-Ca, Hypo-PO4, Hypo-Mg
Mxn of Cidofovir?
Nucleotide analog that inhibits viral DNA polymerase; does not require activation by viral kinase
10-100x more active against CMV in vitro
Half-life of Cidofovir?
long half-life
Indications for Cidofovir?
Ganciclovir-resistant CMV
Acyclovir-resistant HSV
Molluscum contagiosum
Pox viruses (small pox, vaccinia, monkeypox)
Mxn of resistance for Cidofovir?
Mutated DNA polymerase
Side effect of Cidofovir? ways to prevent it from happening?
Nephrotoxicity (coadminister with probenecid and IV saline to toxicity)
What is Interferon α and its mechanism of action?
glycoproteins with anti-viral and anti-tumor properties; inhibits viral replication and promotes cytotoxic T cell and NK cell activity
Indications for Interferon α?
Hep B, C
Kaposi Sarcoma
Hairy cell leukemia
Conyloma acuminatum
Side effects of Interferon α?
Neutropenia
Myopathy
Flu-like symptoms
What are Boceprevir and Telapravir?
Protease inhibitor that forms a covalent bond with NS3 protease and prevents it from cleaving the HCV polyprotein into functional viral proteins
Indications for Boceprevir and Telapravir?
HCV – one very specific type only
ADR for Boceprevir and Telapravir?
Boceprevir – anemia, pancytopenia
Telapravir – anemia, pruritus, skin rash
Influenza
Primary treatment
Zanamivir
Oseltamivir
HSV
Primary treatment
Alternate Drugs
Drugs for resistant strains
Acyclovir
Famciclovir
Valacyclovir
Cidofovir
Foscarnet
VZV
Primary treatment
Alternate Drugs
Famciclovir*
Acyclovir
Valacyclovir
CMV
Primary treatment
Alternate Drugs
Ganciclovir
Valganciclovir –prophylaxis in immunocompromised hosts
Cidofovir
Foscarnet
HepB
Primary treatment
Alternate Drugs
Drugs for resistant strains
Interferon α adefovir emtricitabine tenofovir entecavir telbivudine
HepC
Primary treatment
Alternate Drugs
Interferon α + Ribavirin
Boceprevir
Telapravir