Exam 4 - Anti-Virals (except HIV) Flashcards
Anti-Herpes/CMV
DRUG LIST
- acyclovir
- ganciclovir
- foscarnet
Anti-Hepatitis
DRUG LIST
- interferons
- ribavirin
- simepravir
- sofosbuvir
- ledipasvir/sofosbuvir
Anti-influenza
DRUG LIST
- amantadine
- oseltamavir
- zanamivir
Anti-Herpes
acyclovir
mechanism
- nucleoside analog (guanosine)
- 1st phosphorylation done by virus (viral thymidine kinase)
- acyclovir has specificity for viral thymidine kinase
- DNA synth inhibition (chain termination)
Anti-herpes
acycolvir
TX targets
- HSV 1/2, VZV
- in vitro activity against EBV, CMV, HHV6
Anti-herpes
acyclovir
ADME
- low bioavailability (take w/ food)
- oral, iv, topical
- renal clearance
- higher dose needed for VZV
- long-term suppression of genital HSV, VZV
- prodrome intervention for orolabial HSV
Anti-herpes
acyclovir
toxicities
- well tolerated
- nausea, diarrhea
Anti-herpes
acyclovir
resistance
-mutation of viral thymidine kinase gene
Anti-CMV
ganciclovir
mechanism
- pretty much identical to acyclovir
- 100x more effective against CMV than acyclovir
Anti-CMV
ganciclovir
administration
IV, intraocular (retinitis)
Anti-CMV
ganciclovir
indications
- prophylaxis post transplantation
- Kaposi’s sarcoma prophylaxis (AIDS)
- CMV-induced retinitis, colitis, esophagitis, pneumonitis
Anti-CMV
ganciclovir
toxicities
myelosuppression, carcinogenic
Anti-CMV
ganciclovir
resistance
-mutation of viral thymidine kinase gene
Anti-herpes/CMV
foscarnet
mechanism
- pyrophosphate analog
- inhibits Viral DNA and RNA polymerases
- 100x greater affinity for viral DNA pol
Anti-herpes/CMV
foscarnet
administration
IV only
Anti-herpes/CMV
foscarnet
indictations
- ayclovir resistant herpes
- CMV retinitis (co-rx w/ acyclovir)
- VZV (off-label)
Anti-herpes/CMV
foscarnet
toxicities
- renal toxicity
- hyperphospatemia, hypo-calcemia/kalemia/magnesemia
- chromosome damage, seizurex, arrhythmias
Antihepatitis
Classes
1) Ribavirin
2) PEG interferon
3) HCVProtease Inhibs (Simeprevir)
4) HCV Polymerase Inhibs (Sofosbuvir/Ledipasvir)
Antihepatitis
PEG interferons
mechanism
-PEG increases half-life/bioavailability
-binds interpheron alpha receptor
-induces intracell signal to inhibit viral genome
tranlation/trancription/release
-increases MHC complex antigens
-stims macrophages
-CD8 T cell proliferation
Antihepatitis
PEG interferons
adminstration
SC or IM
Antihepatitis
PEG interferons
toxicities/adverse
-flu-like symptoms (“patients will hit you” - O’Brien),
elevation of hepatic enzymes
Antihepatitis
PEG interferons
contraindications
-liver dz, autoimmune dz, arrhythmia, pregancy (abortifacient)
Antihepatitis
Ribavirin
mechanism
- guanosine analog
- blocks capping of viral mRNA
Antihepatitis
Ribavirin
administration
oral pro-drug
Antihepatitis
Ribavirin
tocixities/adverse
-hemolytic anemia occurs in 15% pts
Antihepatitis
Ribavirin
contraindications
-teratogenic, embryotoxic, mutagenic
Antihepatitis
Simeprevir
mechanism
-protease inhibitors (NS3/4A)
Antihepatitis
Simeprevir
toxicities
-rash, photosens, bilirubinemia
Antihepatitis
Simeprevir
contraindications
- prolly preggercy
- rosuva/atorvastatin
Antihepatitis
Sofosbuvir
mechanism
- uridine analog
- inhibits RNA polymerase
- combo with PEG and ribavirin (likely exclude PEG soon)
- probably to be combo’d with ledipsavir alone soon
Antihepatitis
Sofosbuvir
toxicities
- well tolerated
- side effects hard to separate from PEG/rib
Antihepatitis
Sofosbuvir
contraindications
-rifampin
Antiinfluenza
adamantanes
mechanism
-inhibit uncoating of viral RNA
Antiinfluenza
adamantanes
contraindications
- Parkinson’s
- high viral resistance
Antiinfluenza
oseltamivir/zanamivir
mechanism
- neuramidase inhibitors (sialic acid analogs)
- sialic acid necessary for viral release
Antiinfluenza
oseltamivir/zanamivir
indications
- influenza A/B
- zanamivir for oseltamivir resistant strains
- oseltamivir for 1yo+
- zanamivir for 7yo+
