Antiviral Agents Flashcards
What is the primary means to control viral spread?
Public health measures as well as prophylactic vaccines.
How does influenza enter the host cell?
Hemagglutinin binds to the cell and the virus is endocytosis
What happens when the endosome containing the influenza virus is acidified?
Two things: First there is a conformational change in hemagglutinin structure that mediates fusion between the influenza viral envelope and the endosomal membranes. Then, activation of viral M2 proton channel elicits the release of RNA genome.
What two processes occur in order for the influenza to egress from the host cell?
- Hemagglutinin interacts with cellular sialic acid moieties.
2.Viral envelope-bound neuraminidases cleave the sequestered sialic acid moieties.
Viral release
What are the three inhibitors of viral neuraminidase?
- Oseltamivir (Tamiflu)
- Zanamivir (Relenza)
- Peramivir (Rapivab)
What does the inhibition of the enzyme neuraminidase lead to?
Virus aggregates at cell surface decreasing both intracellular viral translocation and viral budding
Is resistance to inhibition of viral neuraminidase a particular problem?
Yes, but it is relatively rare 1-4%
Describe the pharmacokinetics of Oselamivir.
Oseltamivir is an oral prodrug excreted renally
Describe the pharmacokinetics of Zanamivir.
Zanamivir is inhaled and eliminated renally
Describe the pharmacokinetics of Peramivir.
Peramivir is given as a single IV dose
What type of influenza does neuramindase inhibitors, inhibit?
Both influenza A and B
What are two drugs that inhibit the uncoating of influenza in the host cell?
Amantadine (Symmetrel) and Rimantadine (Flumadine)
What is the target of amantadin and rimantadine?
Blocks the proton channel M2
Describe the pharmacokinetics of amantadine.
Orally. Excreted renally
Describe the pharmacokinetics of rimantadine.
Orally with hepatic elimination
What group would you not prescribe amantadine or rimantadine.
Breast feeding mother. It is excreted through breast milk
What type of influenza is used amantadine or rimantadine used for ?
Type A
Name adverse reactions of amantadine and rimantadine.
Amantadine- insomnia, [] difficulties,
Rimantadine- poor CNS penetration. Not for use in pregnant women
Acyclovir, Valacyclovir, Penciclovir, and Famciclovir are all examples of what?
Inhibitors of viral genome replication in the treatment of herpes infection.
What enzyme converts nucleoside analogs to the active triphosphate form?
VIRAL thymidine kinase
What drug competes with dGTP to terminate viral replication? Hint: It also irreversibly binds and inactivates viral DNA polymerase
Acyclovir-TP
How do herpes viruses gain resistance to inhibitors of viral genome?
They reduce or loose expression of viral thymidine kinase
What are the pharmacokinetics of viral inhibition of replication drugs?
Acyclovir- Poor oral, IV or topical
Valacyclovir- prodrug or acyclovir oral (3-5X)
Penciclovir- Topical only
Famciclovir- Penciclovir prodrug. Increased oral bioavailability
Vidarabine-trifluidine- topical
How are viral inhibition of replication drugs eliminated?
Renally but clearance in neonates is 1/3 of adults
How would you treat genital herpes?
Oral acyclovir
When would you use intravenous acyclovir?
To treat herpes simplex encephalitis, neonatal HSV infections, and serious HSV or VZA infections (higher doses required for zoster)
What would you use to treat HSV keratoconjunctivitis and reccuent epithelial keratitis?
Topical vidarabine and trifluridine
Name a drug that inhibits viral penetration.
Docosanol
How does docosanol prevent viral penetration?
They prevent the fusion of viral and host membrane. Used topically for orofacial herpes.
What drug is used for the treatment of respiratory syncitial virus?
Ribavirin
What is ribavirin?
A purine nucleoside analog that inhibits GTP-dependent 5’ capping of viral mRNA.
What are the pharmacokinetics of ribavirin?
Oral bioavailability good. Hepatic metabolism and renal excretion.
What are the adverse reactions of Ribavirin?
Inhalation: fine
Oral-systemic: hemolytic anemia
TERATOGENIC = NO PREGNANT WOMEN
How would you treat hepatitis C
Ribavirin with interferon
What is the action of Ganciclovir and Valganciclovir?
Inhibition of viral DNA polymerase. Nucleotide analog.
Ganciclovir and Valganciclovir must be phosphorylated in order to become activate. What enzyme phosphorylates these drugs and is it the target for resistance?
The enzyme is Viral protein kinase UL97 and it is the target for resistance.
Describe the pharmacokinetics of Ganciclovir and Valganciclovir.
Ganciclovir- IV primarily excreted unchanged via urine
Valganciclovir- prodrug converted to ganciclovir by GI and hepatic enzymes
What is the major side effect or concern with using ganciclovir or valganciclovir?
They are myelocuppressive and result in neutropenia and thrombocytopenia
What two drugs can be used to treat cytomegalovirus?
Ganciclovir/Valganciclovir and Foscarnet
Describe foscarnet.
Inorganic pyrophosphate analog that does not require cellular activation.
What is the action of foscarnet?
It inhibits the cleavage of pyrophosphate from deoxxy-TP= block in replication
How is foscarnet administered?
IV infusion and is eliminated via the urine
What are some of the severe side effects you need to worry about when using foscarnet?
Nephrotoxicity and hypocalcemia can lead to death
