Pharm Anti-virals Flashcards
Acyclovir (Spectrum)
Anti-viral (15-21% bioavailability)
Herpes simplex (HSV) 1 and 2
Varicella-zoster (VZV)
EBV
Not CMV
Famciclovir (Spectrum)
Anti-viral (77% bioavailability)
Herpes simplex (HSV) 1 and 2
Varicella-zoster (VZV)
EBV
Not CMV
Ganciclovir (Spectrum)
Active against cytomegalovirus (CMV)
Poor bioavailability (5-9%)
Foscarnet (Spectrum)
Anti-viral
GCV resistant CMV,
ACV-resistant HSV 1&2, VZV
Intolerable myelosuppression with GCV
Valacyclovir
Prodrug of Acyclovir combined with valine
Improved bioavailability to 54% but 5x more expensive
Famciclovir
Prodrug of penciclovir
Improved oral bioavailability over ACV of 77%
Oral treatment of VZV
Valaganciclovir
Prodrug, valine ester of Ganciclovir
Improved bioavailability to 60%
Foscarnet (MOA)
Inorganic pyrophosphate analog
Directly inhibits viral DNA polymerase (Reversibly blocks pyrophosphate binding site of viral DNA polymerase)
Renal metabolism
Acyclovir (MOA)
Deoxyguanosine nucleotide analog that inhibits transcription by viral DNA polymerase
Renal metabolism
Ganciclovir (MOA)
Deoxyguanosine nucleotide analog that inhibits transcription by viral DNA polymerase
Renal metabolism
Acyclovir (Toxicity)
Rare, not significant
Nephrotoxicity: can crystallize in renal tubules
Neurotoxicity: lethargy, confusion, delirium
ACV Resistance
Due to loss of viral thymidine kinase, altered TK activity, or DNA polymerase mutants
ACV-R HSV or VSV will be cross-resistant to famciclovir and ganciclovir
Ganciclovir (Toxicity)
Myelosuppression (Neutropenia and thrombocytopenia) CNS toxicity (Headache, change in mental status)
Ganciclovir Resistance
Reduced intracellular phosphorylation due to point mutations/deletions in the UL97 gene
Point mutations in the viral DNA polymerase
Cross resistance to Foscarnet
Foscarnet (Toxicity)
Very significant
Nephrotoxicity (usually 2nd week of therapy)
- Reversible
Metabolic abnormalities
- Hypocalcemia
- Hypomagnesemia
- Hypokalemia
CNS abnormalities
- Headache, irritability, seizures
Painful genital ulcerations
Hep B Therapy Drugs
Lamivudine/emtricitabine (Least potent)
Entecavir
Tenofovir (Most potent)
Hep B Drugs (MOA)
Nuceloside analogs: inhibits hepatitis B DNA polymerase via chain termination
Suppresses replication, not a cure
Interferon alpha 2a or 2b (MOA)
Hep C
Induce interferon-stimulated genes which establish an antiviral state within cells, though the response is not virus specific; inhibit viral protein synthesis
Interferon alpha 2a or 2b (Side effects)
- Fever, myalgia
- Neutropenia, thrombocytopenia
- Hypothyroidism
- Depression
Ribavirin (MOA)
Hep C
Nuceloside analog
Ribavirin (Side effects)
- Hemolytic anemia
- Teratogenic
- Flu-like symptoms
- Depression/irritability
- Rash
- Nausea/diarrhea
Interferon + ribavirin (response rates)
Most responsive to least: 2 and 3 4 5 6 1
Interferon + ribavirin (Limitations)
Not well tolerated
Poor response rates
Long duration of therapy (up to 48 weeks)
Hep C Direct Acting Agents
Protease inhibitors
- Boceprevir
- Telaprevir
- Simeprevir
Only used for Genotype 1
Protease Inhibitors benefits
Increase response rates of Interferon and ribavirin therapy
Decreased length of therapy
Harvoni (MOA)
Sofosbuvir (Nucleoside analog against HCV NS5B polymerase)
Ledipasvir (NS5A inhibitor)
Harvoni (Spectrum)
HCV genotypes 1, 4, 5, and 6
Zapatier (MOA)
Elbasvir (NS5A inhibitor)
Grazoprevir (NS3/NS4A inhibitor)
Zapatier (Spectrum)
HCV Genotypes 1 and 4
Epclusa (MOA)
Sofosbuvir (Nucleoside analog against HCV NS5B polymerase)
Velpatsavir (NS5A inhibitor)
Epclusa (Spectrum)
Pan-Genotypic
HCV Genotypes 1, 2, 3, 4, 5, 6
Mayret (MOA)
Glecabrevir (NS3/4A protease inhibitor)
Pribrentasvir (NS5A inhibitor)
Mayret (Spectrum)
Pan-Genotypic
HCV Genotypes 1, 2, 3, 4, 5, 6
