Antivirals Flashcards
What is the difference between acyclovir and valacyclovir?
Val form is a prodrug that gets converted to acyclovir. It is oral, and has a higher bioavailability.
(Why even use acyclovir)
What is required for acyclovir/valacyclovir to be active?
Must be phosphoryltateed and “trapped” in the cell by viral thymidine kinase
How does herpes develop resistance to acyclovir/valacyclovir?
Decreases the amount of/mutates thymidine kinase
The enzyme that phosphorylates and traps the drug
Which nucleotide is acyclovir/valacyclovir an analogue of?
Guanosine
What is the difference between antiviral vs antiretroviral?
Antiretrovirals are for HIV only
Why are acyclovir/valacyclovir such safe drugs?
They are only active once virus-infected cells take them in and phosphorylate them, and then they are trapped in the cell and won’t come back out.
If you see herpes, what drug are you giving?
Acyclovir/valacyclovir
What is the main side effect of acyclovir/valacyclovir?
What can you do to offset it?
Nephrotoxicity in ~high IV~ doses
Hydrate aggressively to prevent this
What is the MOA of docosanol (abreva)?
Inhibits viral fusion to host cell plasma membrane
Docosanol (Abreva) kind of sucks for cold sores. Why is it important?
Because it’s cheap and OTC and might be the only option for some people
(Definitely not the DOC…. that would be acyclovir/valacyclovir becasue it’s herpes)
Ganciclovir and valgancyclovir do the same thing. What is the difference between them?
Valgancyclovir is an oral alternative that is a prodrug with higher bioavailability (just like acyclovir and Val)
(Ganciclovir is oral, IV or ocular implant)
What diseases will be treated by ganciclovir/valgancyclovir?
CMV and herpes
Just wont be as effective for herpes as acyclovir
What can be used as treatment or prophylaxis of CMV and herpes in transplant patients or HIV+ patients?
Ganciclovir
Can we give ganciclovir/valgancyclovir to pregnant women?
No
What are the drugs that can be used for CMV and/or herpes?
Ganciclovir/valgancyclovir
Foscarnet
Cidofovir
What nucleotide is ganciclovir/valgancyclovir an analogue of?
Guanosine
Is ganciclovir/valgancyclovir active when you take it?
No, it must be activated by CMV phospotransferase or Herpes thymidine kinase
How would CMV develop resistance to ganciclovir/valgancyclovir?
Mutate the CMV phosphotransferase that activates the drug
Every drug that treats CMV will treat _______
Herpes (just not as effectively as acyclovir and you would only use this to treat herpes if the pt was also infected with CMV)
Why is ganciclovir/valgancyclovir useful against herpes and CMV?
Because the drug can be activated by herpes thymine kinase or CMV phosphotransferase
Ok, so i get it: CMV or herpes enzymes activate ganciclovir/valgancyclovir by doing the first phosphorylation. But how does the drug get the next two phosphorylation it needs?
Host enzymes
Same thing as acyclovir for herpes
What are the main side effects of ganciclovir/valgancyclovir?
CNS- headache, confusion, seizures
Also myelosuppression- low RBC, WBCs, and platelets
but main one she said is CNS
Oh shit your CMV has mutated its phosphotransferase, and now it won’t activate ganciclovir. Now how are we supposed to treat it?
Foscarnet or Cidofovir
Don’t require phosphorylation for activity
What is the MOA of foscarnet?
Directly inhibits DNA&RNA polymerase and reverse transcriptase
What nucleotide is cidofovir an analogue of?
Cytosine
If you want to use oseltamivir or zanamivir for the treatment of influenza, when do you need to do it?
EARLY. Within 48 hours of symptoms
Your patient comes to you with a flu that she’s been dealing with for a week. She is demanding Tamiflu. What do you do?
You can’t give it to her because it’s already been a week. Oseltamivir and zanamavir need to be given within 48 hours of symptoms
You have a patient that shows up with flu symptoms that she’s been having for 24 hours. She has a history of asthma and wants some sort of treatment for her flu. What do you do?
You can give her Oseltamivir becasue she’s had symptoms for less than 48 hours. BUT you can NOTTTTTT give her zanamaivr because it is given through an inhaler and thats not OK for someone with respiratory issues
What is the MOA of oseltamivir and zanamvir ?
Neuraminidase inhibitors. They block the release of the virus from cells
You’ve acquiesced to your patient’s demands and given her oseltamivir for her flu. What side effects do you need to warn her about?
Nausea and vomiting are common
What do you use to treat RSV?
Ribavirin
What is the MOA of ribavirin?
Inhibits RNA polymerase
What nucleotide is ribavirin an analogue of?
Guanosine
Ribavirin needs to be phosphorylated _____times. Who does these phosphorylations?
3 times. Host does all 3
What is the one drug we talked about that carries a huge occupational risk for healthcare workers?
Ribavirin, due to its extreme teratogenicity. You can not conceive for at least 6 months after exposure to this drug.
How is ribavirin usually administered?
In tented room. (Usually given only to kids and infants)
What are the 3 drugs that treat hepatitis B?
Tenofovir
Entecavir
Lamivudine
Which hepatitis B drugs also treat HIV?
Tenofovir
Lamivudine
What is the DOC for hepatitis B?
Tenofovir
What nucleotide analogue is tenofovir/
Adenosine
What nucleotide analogue is entecavir
Guanosine
What nucleotide analogue is lamivudine?
Cytosine
Will tenofovir, entecavir, or lamivudine CURE your hepatitis B?
No! Just suppresses hepatic inflammation and virus replication
~No cure~ 😥
Oh shit you have hepatitis C and you are wealthy and want a cure. What drug do you want?
Harvoni
How does harvoni ~cure~ hepatitis C?
It blocks replication and assembly of the virus
