AntiViral-Table 1 Flashcards
What are viruses hard to tx?
- Effective treatment requires that the drug must enter the host cell
- Most antivirals agents inhibit single steps in viral replication and are virustatic- need competent host immune system
What are the inhibitors of viral attachment (uncoating or release)?
Docosanol Amantadine Rimantadine Oseltamivir Zanamivir Peramivir
What are the inhibitors of viral attachment?
Amantadine and Rimantadine
What is the MOA of the inhibitors of viral attachment?
¨Bind viral protein M2 and inhibit viral uncoating
How are the inhibitors of viral attachment used?
for treatment and prophylaxis of influenza type A, no effect on type B-lack M2
Do the inhibitors of viral attachment have a wide or narrow therapeutic index? Why is this important to know?
Narrow therapeutic index
(therapeutic 0.5-0.8mcg/mL, CNS toxic >1-5 mcg/mL)
this is important bc of the cns toxic effects- seizure, coma, delirium
When is amantadine specifically used?
Parkinsons
How is amatadine excreted?
Majority Unchanged in the urine
How is RImantadine metabolized?
Liver
What are the neuroaminidase inhibitors?
Oseltamivir, Zanamivir, Peramivir
What is the MOA of the neuroaminidase inhibitors?
Selective inhibitors of viral neuraminidases which are essential for release of virus from the infected cell
What are the neuroaminidase inhibitors used for?
¨Treatment of influenza A and B, duration 5 days
can be effective prophylactically before or after exposure to influenza A/B
How is oseltamivir administered?
Orally
What are some ADRs of oseltamivir? How can you diminish these?
N/V, take with food
How is Zanamivir administered?
Intranasal or inhaled dry powder
What can be an ADR of Zanamivir? Which pts should you prescribe this with caution in?
produce bronchospasms
careful in patients with asthma or COPD
How is Peramivir administered?
IV
What is an ADR of Peramivir ?
Diarrhea
What drug inhibits attachement?
DOcosanol- prevents viral attachment to human cell
How is Docosanol administered?
OTC creamw
What is docosanol used for and when should it be started?
Oral/genital herpes
Begin tx within 12 hrs of prodromal symptoms or lesion onset
What are the drug categories that block DNA synthesis from viral DNA?
Guanosine analog and Cytosine Analog
What are the above drug groups active against?
Herpes family
What are the guanosine analogs?
¨Acyclovir ¨Valacyclovir ¨Penciclovir ¨Famiciclovir ¨Ganciclovir Valganciclovir
What are the cytosine analogs?
Cidfovir
What is the mechanism of viral resistance in nAcyclovir, Valacyclovir, Penciclovir, Ganciclovir, Valganciclovir?
Phosphorylated by viral thymidine kinase
What is the oral prodrug of acyclovir?
Valcyclovir
What are acyclovir and valcyclovir used for?
-Treatment and Prophylaxis of:
Herpes simplex (type I and II) and zoster
Varicella zoster- treatment
When do val/acyc need to be administered to a pt with varicella zoster?
w/I 24hrs of rash onset to decrease symptoms by day 1
What is the DOC for HVS infections?
Val/acyc
What pts is acyclovir used prophylactically in?
Seropositive pts undergoing immunosuppressive therapy- prevent mucocutaneous HSV infections
When are penciclorvir and famciclovir used?
to treat Herpes Zoster, Herpes simplex type II, topical treatment of oral/labial herpes simplex virus
How are ganciclovir and valganciclovir phosphorylated?
by viral protein kinase in cytomegalovirus and by viral thymidine kinase in herpes simplex virus then further phosphorylated by host enzymes
What are ganciclovir and valganciclovir active against?
All herpes viruses
What are ganciclovir and valganciclovir used to tx specifically?
CMV in immunocompromised pts
What are some ADRs of ganciclovir and valganciclovir?
Neutropenia, thrombocytopenia, teratogenic
What is vitasert?
an intraocular sustained release implant for CMV retinitis (ganciclovir and valganciclovir?)
How is cidofovir phosphorylated?
by host enzymes- males this useful when viral thymidine kinase resistance has developed
What is the spectrum of activity for cidofovir?
Broad spectrum: herpes and pox viruses, adenoviruses, papilloma viruses, and hepadenavirus
What is cidofovir primarily used for?
treatment of cytomegalovirus in AIDS patients who are intolerant, relapsed, or nonresponsive to ganciclovir or foscarnet
AND
Acyclovir resistant mucocutaneous HSV infection
What are the ADRs of cidofovir?
Neutropenia and nephrotoxicity
What are the nucleotide analogs?
Adefovir and tenofovir
What is adefovir used for?
treatment of chronic active infections HepB
Does adefovir need to be phosphorylated?
this drug does NOT require phosphorylation
How is tenofovir processed?
Hydrolysis then phosphorylation
What is tenofovir used for?
HIV and Hep B tx
What is foscarnet?
-an inorganic phosphate analog that acts by directly inhibiting DNA and RNA polymerases and reverse transcriptases- 100 x greater effect on viral vs human DNA polymerase
Does foscarnet require phosphorylation?
Nope
What is foscarnet active against?
all herpes viruses, influenza, and HIV
What are the primary uses of foscarnet?
CMV infections, acyclovir resistant herpes simplex or varicella zoster
How is foscarnet administered?
Infusion in large volume of fluid
What are the ADRs of Foscarnet?
-Nephrotoxicity- dose limiting in 10-25% of patients
¨Increased risk with amphotericin B and aminoglycosides
What is Ribavirin?
A purine nucleoside analog that is phosphorylated intracellularly by host cell enzymes
What is ribavirin aerosol used to tx?
RSV
What is ribavirin plus peginterferon used for?
Tx of Hep C
What are interferons?
Immunomodulatory and antiviral drugs that are non-specific inhibitors of RNA and protein synthesis- basically it prevents translation of viral proteins
What are the dose limiting toxicities of interferons?
- Neutropenia and anemia
- Flu like syndrome”- fever, fatigue, myalgia
Interferon A/B are produced by almost all cells in response to what?
Viral infection
What produces interferon Gamma?
T-cells and NK cells in response to antigens and cytokines
What is interferon A used for?
Chronic Hep C/B
Genital warts from papilloma virus
Hariy cell leukemia
Kaposis sarcoma
What is interferon B used for?
Remitting MS
What is interferon Y(gamma) used for?
Chronic granulomatous disease
