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.
What is a rare side effect that can happen when using IV or oral Acyclovir? Tx moving forewords and why?
Crystalluria, or the presence of crystals in the urine. This can lead to severe dehydration and IV hydration is strongly advised, possibly removing the drug as well.
5 rare side effects for Acyclovir
Neurotoxicity, seizures, anemia and leukopenia, neutropenia
Rare side effects for Cidofovir (2)?
Nephrotoxicity and Neutropenia
Rare side effects for Foscarnet (2)
Nephrotoxicity and Seizures (electrolyte imbalances)
Rare side effects for Ganciclovir (3)?
Neurotoxicity, Neutropenia, Anemia
Rare side effects for Valacyclovir (2)?
Increased ALT and AST, Neutropenia
Rare side effects for Valganciclovir (3)?
Neutropenia, Anemia, Thrombocytopenia
Which 2 of the great 7 antivirals are kryptonite by Mutations in DNA polymerase?
Famciclovir and Ganciclovir
Which 5 of the great 7 antivirals are kryptonite by alteration in thymidine kinase and/or DNA polymerase?
Acyclovir, Famciclovir, Ganciclovir, Valacyclovir and Valganciclovir
Acronym for the 7 antivirals we discuss?
Fucking Vince Vaughn Can Always Get Funny
Famciclovir, Valacyclovir, Valganciclovir, Cidofovir, Acyclovir, Ganciclovir, Foscarnet
Which two antivirals can cause nephrotoxicity and what should you do in that case?
Acyclovir and Foscarnet, hydrate with IV fluids.
Which two antivirals are carcinogenic and Teratogenic?
Cifofovir and Ganciclovir
Which two antivirals require females to use contraceptives 30 days post-therapy and makes to use barriers?
Ganciclovir and Valganciclovir
