Antiviral Drugs Flashcards
How would you administer Acyclovir for someone who presents with genital herpes (HSV-2)?
orally
How would you administer Acyclovir for someone who presents with herpes infection of face and mouth?
orally; usually reserved for immunocompromised patients
When is IV acyclovir used?
for immunosuppressed patients with chicken pox or with shingles
MOA for Acyclovir
- prodrug converted to acyclo-guanidine triphosphate (active) by thymidine kinase
- sequential phosphorylation by cellular enzymes to acyclo-GTP
- acyclo-GTP inhibits viral DNA polymerase, and is incorporated into viral DNA resulting in chain termination –> replication is blocked
Is acyclo-GTP more selective for viral or human DNA polymerases?
viral
What are 3 mechanisms of drug resistance for acyclovir?
- thymidine kinase mutation (viruses that do not activate acyclovir)
- decreased viral expression of thymidine kinase
- mutation and selection of viral DNA pol that are not inhibited as well by acyclo-GTP
What are adverse effects of topical and oral administration of acyclovir? IV?
- topical - transient burning sensation
- oral - nausea, diarrhea, HA, vertigo
- reversible kidney damage that presents with high creatine and urea levels
How can kidney damage be minimized during IV administration of acyclovir?
- slow infusion (1hour)
- adequate hydration
- avoiding co-administration with other nephrotoxic drugs
What is a contraindication for acyclovir administration?
avoiding IV co-administration with other nephrotoxic drugs
What is the active form of acyclovir?
acyclovir triphosphate
What are 2 other drugs for herpes that are prodrugs of acyclovir?
- valacyclovir
- famiciclovir
*both have better oral availability
What are topical drugs for ocular herpes?
What do they all have in common?
- ganciclovir or acyclovir
- trifluridine
- brivudine
- vidarabine
inhibit viral DNA synthesis
When would you administer vidarabine?
acute kertoconjunctivitis and recurrent keratitis caused by HSV 1 or 2
Which topical drug for ocular herpes causes edema of the eyelid in 3% of patients and is not absorbed systemically?
trifluridine
Ganciclovir is a drug for _____. Availability? Adverse effects?
cytomegalovirus
available orally and IV
granulocytopenia and thrombocytopenia; should not be used during pregnancy
Ganciclovir is approved for prophylactic use in _____.
organ transplant patients
Describe the MOA of ganciclovir.
- converted to monophosphate by viral deoxyguanosine kinase (in CMV infected cells)
- cellular kinases convert to triphosphate
- ganciclovir triphosphate inhibits viral DNA polymerase (more selectively the human pol) and incorporates into the DNA resulting in chain termination —> viral replication blocked
What are contraindications of ganciclovir?
- coadministration with zidovudine exacerbates granulocytopenia and thrombocytopenia
- coadministration with G-CSF can reduce granulocytopenia
What are other drugs for CMV? (x3) Give some facts about each.
- valganciclovir (prodrug of ganciclovir)
- better oral availability; just as effective for CMV retinitis as IV ganciclovir - cidofovir
- approved for only one indiction (CMV retinitis in AIDS patients)
- MOA converted to diphosphate and inhibits viral DNA pol - foscarnet
- approved uses are CMV retinitis in AIDS patients
- nephrotoxic
What is the clinical use of Fomivirsen?
CMV retinitis in patients that do not respond to another drug
MOA for Fomivirsen
antisense drug
inhibits the replication of CMV by binding to the complimentary sequence of mRNA transcribed by CMV; inhibits synthesis of proteins that are essential for production of infection CMV
What an adverse effect of Fomivirsen
ocular inflammation
For which Hepatitis is there not a vaccine for?
Hep C
What is the preferred drug for Hep B?
Entecavir
Drugs for Hep B are ______ and inhibit _______.
nucleoside analogs that inhibit Hep B reverse transcriptase
What are the effects of Lamivudine on Hep B infections?
- suppresses viral réplication (but is not a cure)
- reduces liver inflammation
- long term use leads to resistance
What is the active form of entecavir and what does it do?
lamivudine triphosphate - incorporates into viral DNA by HBV reverse transcriptase resulting in DNA chain termination
What is the prodrug of tenofovir for Hep B?
tenofovir disoproxil
Tenofovir is an NRTI. What does NRTI stand for?
nucleotide analog reverse transcriptase inhibitor
_______ is used for both HIV and Hep B
tenofovir
Hep C and HIV require _____ drug treatment for two reasons:
combination drug treatment bc:
- better blocking of viral replication - wha the first drug doesn’t block may be blocked by the second drug
- drug resistance is less likely to arise
What are the 3 current drugs for Hep C? (older ones were PEG-IFN and ribavirin)
which step in replication does each drug inhibit?
- viral protease inhibitors (Simeprevir)
- inhibits translation/processing
- Viral RNA polymerase inhibitors / chain termination (Sofosbuvir)
- inhibits replication
- NS5a protein inhibitor (Ledipasvir)
- inhibits morphogenesis; NS5A protein plays important role in viral rep, assembly, secretion
What is the adverse effect of PEG-IFN?
flu like sxs (bc interferon alpha binds to receptors of infected cells) and depression
What is an adverse effect of ribavirin?
hemolytic anemia
What are the two types of vaccines available for influenza A and B?
inactivated influenza vaccine
attenuated live vaccine (intranasal spray)
What are the two classes of drugs for influenza?
- Adamantanes
- amantadine and rimantadine - neuraminidase inhibitors
- oseltamivir (tamiflu) and zanamivir (relenza)
In the influenza virus, amantadine blocks ____ and neuraminidase blocks ______.
amantadine blocks proton channel
neuraminidase blocks budding
True or false: amantadine and rimantadine are active against Influenza A but not against Influenza B.
true
What is the MOA for amandine/rimantadine
inhibit viral M2 proton channels, virus taken up by endosomes - viruses cannot acidify and uncoat
Which neuraminidase inhibitor should not be used in asthma patients to treat influenza?
zanamavir
What are used for prophylaxis of family members/nursing home patients?
neuraminidase inhibitors such as oseltamivir (tamiflu) and zanamivir (relenza)
What is the MOA for neuraminidase inhibitors?
normally, neuraminidase catalyzes cleavage of silica acid residues on the surface of host cells and influenza virus - required for release of viral progeny
neuraminidase inhibitors block this - inhibitors are analogs of silica acid
Must begin treatment of neuraminidase inhibitors within _______ of sxs to improve outcomes.
within 2 days of symptoms
