Pharmacology Week 1 Flashcards
How do antivirals work? 3 ways
They either block entry into the cell, block entry out of the cell, or work inside of the cell by blocking.
They ONLY work on replicating viruses, not dormant ones.
4 methods that antivirals work inside of the cell
blocking nucleic acid synthesis, blocking integration (transcription), and blocking viral protein synthesis.
What 4 antivirals inhibit viral DNA synthesis?
Famciclovir, Granciclovir, Valacyclovir, and Valganciclovir
Which antiviral inhibits viral RNA and DNA polymerase? Which antiviral suppresses CMV replication by selective inhibition of viral DNA synthesis?
Foscarnet inhibits viral RNA and DNA polymerase and Cidofovir suppresses CMV replication by selective inhibition of viral DNA synthesis
Which antivirals can be used to treat Herpes Simplex (HSV)?
Acyclovir, Famciclovir, Foscarnet, Ganciclovir, Valacyclovir, Valganciclovir
What one antiviral out of the great 7 does not treat CMV
Famciclovir
What 2 antivirals can treat shingles?
Valacyclovir (valtrex) and Acyclovir (Zovirax)
How do antivirals inhibit viral DNA polymerase?
They are considered “antimetabolites” which means they mimic the nucleoside structure (Sugar, base) and insert themselves into replication and halt it.
Antimetabolites = incorrect DNA building blocks
What is a Prodrug? Give two examples. What do Valcyclovir and Famciclvir become?
Famciclovir and Valacyclovir are prodrugs, meaning they are inactive until metabolized.
Valacyclovir becomes Acyclovir after enzymatic hydrolysis in the liver.
Famciclovir becomes Penciclovir.
Describe the trio of phosphorylations for antivirals? STEP 1 of the mechanism of action.
Antivirals enter cells (such as infected by Herpes simplex or VZV) and the antimetabolite under a phosphorylation by viral thymidine Kinase and then two phosphorylations by Cellular kinase.
This makes the compound polar so it cannot leave the cell and accumulates inside.
Antiviral mechanism of action, STEP 2
Once the antimetabolite is activated and enters the Viral DNA, there is DNA termination because although it has the sugar and base, there is no 3’ hydroxyl on the Acyclovir monophosphate group which is needed for continued replication. It competed with 3-guanosine
Full MECHANISM of Acyclovir.
In an infected HCMV (Cytomegalovirus) cell, what viral protein kinase performs the initial phosphorylation of Ganciclovir?
HCMV protein kinase.
Why does Cidofovir (CDV) skip the first phosphorylation step?
It already has a a phosphate group attached. All it needs is the Cellar kinases for two further phosphorylations to triphosphate form.
How does Foscarnet work?
Foscarnet blocks HCMV DNA polymerase as a noncompetitive inhibitor at the pyrophosphate binding site for viral RNA and viral DNA.
It DOES NOT require phosphorylation activation by either the viral protein kinases or intracellular kinases.
