P2 Spring Pcol2 02-15 And 02-16 And 02-22

Front 1

List two differences between DNA and RNA viruses

Back 1

DNA viruses use the host's RNA polymerase for transcription, RNA viruses bring their own viral RNA polymerase for transcription
DNA virusus enter the nucleus, RNA viruses stay in the cytoplasm (for the most part)

Front 2

Whats the difference between enveloped and nonenveloped viruses in how they enter/infect a host cell?

Back 2

Enveloped viruses fuse with the host cell membrane, leaving their envelope behind (as part of the host membrane) upon entering.
Nonenveloped viruses enter the cell via endocytosis.

Front 3

Whats the difference between how enveloped and nonenveloped viruses exit the host cell?

Back 3

Enveloped viruses leave via exocytosis, taking part of the host cell membrane with them as their new envelope
Nonenveloped viruses wait until the cell bursts (via cell lysis)

Front 4

How do antiviral drugs kill viruses?

Back 4

Trick question
Antivirals dont kill viruses, they just provent their proliferation.
The host defenses must clear the viruses.

Front 5

List the different herpes viruses

Back 5

Herpes simplex 1 and 2 (HSV 1 and HSV 2)
Herpesvirus 6
Varicella zoster virus
Cytomegalovirus(CMV)
Epstein Barr virus

Front 6

What do all the herpes viruses have in common?

Back 6

They are all LYTIC, then LATENT
They have large double stranded DNA genomes
They are enveloped viruses

Front 7

Whats a PRODROME? Why is it important?

Back 7

When you sense an upcoming bout of your infection
You want to take your antivirus at this time to mimimize symptoms

Front 8

What is SHINGLES?

Back 8

Its the adult version of chicken pox (varicella zoster infection)

Front 9

Whats the difference between HSV 1 and HSV 2?

Back 9

HSV 1 is painful lesions (fever blisters) "above the waist"
HSV 2 is painful genital lesions "below the waist"

Front 10

What are the main targets of herpes antiviral drugs?

Back 10

Viral thymidine kinase (TK)
Viral DNA polymerase

Front 11

List as many herpes antiviral drugs as you can

Back 11

Acyclovir
Valacyclovir
Penciclovir
Famciclovir
Ganciclovir
Valganciclovir
Cidofovir
Trifluridine
Foscarnet
Vidarabine

Front 12

Whats the MoA of acyclovir?

Back 12

Prodrug
G analog
Viral TK adds the first phosphate group
Host cell kinases add the last two phosphates
The G mimic/drug is added to the growing DNA chain during DNA synthesis
Viral DNA polymerase binds irreversibly to the mimic
Also causes chain termination

Front 13

Whats chain termination?

Back 13

Cant add another nucleotide base to the DNA strand during synthesis, typically due to the mimic not possessing a 3 prime hydroxyl group to attach the next base to (by design)

Front 14

Whats the MoA of valacyclovir?

Back 14

Pro-prodrug of acyclovir with a valine group added for better oral absorption

Front 15

Whats the MoA of penciclovir?

Back 15

Prodrug
G analog
Phosphorylated by viral TK, then cellular kinases
Inhibits viral DNA polymerase
Everything is the same as acyclovir except there's no chain termination and the DoA(duration of action) is longer than acyclovir

Front 16

Whats the MoA of famciclovir?

Back 16

Pro-prodrug of penciclovir with a valine group added for better oral absorption

Front 17

What are the MoA of resistance to acyclovir?

Back 17

Mutation/SNiPs in viral TK that dec the affinity of acyclovir for TK
Downregulation (to the point of absence) of viral TK
Self alteration (mutation) of viral DNA polymerase

Front 18

Even though penciclovir is only topical, and famciclovir is only oral, they both should be taken during the _____

Back 18

prodrome (prior to the actual outbreak, when you sense tingling, burning, or irritation)

Front 19

Whats the difference in MoA between val/acyclovir and val/ganciclovir?

Back 19

None

Front 20

Whats the difference in indication between val/acyclovir and val/ganciclovir?

Back 20

Val/ganciclovir is used for CMV retinitis and other CMV complications
Val/acyclovir is used for all the herpes viruses, but mostly for HSV and the least for CMV

Front 21

Whats the difference in AE's between val/acyclovir and val/ganciclovir?

Back 21

Val/ganciclovir binds to the host DNA polymerase causing myelosuppression, resulting in neutropenia(40%) and thrombocytopenia
Val/acyclovir just causes N&V, diarrhea, and headaches

Front 22

What are the MoA of resistance to ganciclovir?

Back 22

Mutation in viral DNA polymerase and a CMV kinase

Front 23

Whats the MoA of cidofovir?

Back 23

Not a prodrug
C analog
Inhibits viral DNA polymerase
Chain termination

Front 24

Whats unique about cidofovir compared to the other nucleotide analogs discussed (not including that its a C analog)?

Back 24

Cidofovir can be used for TK resistant strains because it contains a phosphonate group (so it doesnt need to be phosphorylated by viral TK)

Front 25

Whats the MoA of resistance to cidofovir?

Back 25

Mutation in viral DNA polymerase

Front 26

Whats the clinical indication for cidofovir?

Back 26

CMV retinitis in HIV patients (and other severely immunocompromised), just like ganciclovir

Front 27

What are the AE's of cidofovir?

Back 27

Nephrotoxicity (give probenacid to dec accumulation/toxicity in kidneys)
Uveitis(inflammation of the uvea, which is the middle layer of the eye)
Cycloplegia(paralysis of the ciliary muscle of the eye which dec's accommodation)

Front 28

Whats the MoA of foscarnet?

Back 28

Its an inorganic pyrophosphate (not a nucleotide analog like the others)
It inhibits viral DNA polymerase by mimicing a phosphate and binding to the site that normally cleaves off phosphates from nucleotides that are being added to the growing DNA strand

Front 29

What is foscarnet particularly good for?

Back 29

For viral TK resistant herpes virus
Foscarnet has no need to be phosphorylated by viral TK since its a phosphonate (phosphate mimic)

Front 30

List some herpes antiviral drugs that rely on viral TK phosphorylation to be active

Back 30

Acyclovir
Penciclovir
Ganciclovir
and all their pro-prodrug forms as well

Front 31

Whats the MoA of resistance to foscarnet?

Back 31

Mutation in viral DNA polymerase

Front 32

Whats the MoA of trifluridine?

Back 32

A uracil analog
Has two MoA's:
Inhibits thymidylate synthase when in monophosphate form after phosphorylation by viral TK
note: thymidylate synthase normally converts U to T
Inhibits viral DNA polymerase when in triphosphate form

Front 33

Whats the clinical indication for trifluridine?

Back 33

Treats HSV 1 & 2 eye infections only

Front 34

Whats the MoA of the influenza virus entering cells?

Back 34

The influenza cell surface has hemagglutinin that attaches to sialic acid residues on the surface of respiratory cells, then the virus is endocytosed

Front 35

After new influenza virions are created, what must occur befor their release from the infected cell?

Back 35

The viral cell has neuraminidase near the hemagglutinin that cleaves the hemagglutinin-sialic acid attachment

Front 36

What is the difference between the different types of influenza virus?

Back 36

Type A influenza has M2 ion channels
Type B influenza has NB protein
Both of which are drug targets

Front 37

Which influenza types have neuraminidase on their surface?

Back 37

All types

Front 38

Whats the purpose of viral M2 ion channels?

Back 38

They let H+ (in the endosome that fuses with it inside the respiratory cells) enter the virus and "uncoat" it, releasing the viral genome into the cell

Front 39

What are antiviral drugs that target type A influenza infected cells only?

Back 39

Amantadine
Rimantadine

Front 40

Whats the MoA of Amantadine and Rimantadine?

Back 40

They both inhibit viral M2 ion channels so H+ cant enter and uncoat the virus

Front 41

What are antiviral drugs that target type A and B influenza infected cells?

Back 41

Oseltamivir/Tamiflu
Zanamivir/Relenza

Front 42

Whats the MoA of Oseltamivir and Zanamivir?

Back 42

They both sialic acid mimics that bind to and inhibit viral neuraminidase, preventing release of the virus from the host cells

Front 43

Whats the MoA of resistance to Amantadine and Rimantadine?

Back 43

Mutation of viral M2, dec'ing affinity of these drugs to M2

Front 44

Which of the influenza drugs discussed can be used prophylactically?

Back 44

All of them

Front 45

What are the AE's of amantadine and rimantadine?

Back 45

CNS symptoms:
-restlessness
-agitation
-insomnia
-seizures(rare)
-suicide ideation(rare)

Front 46

Which of the 4 influenza drugs is a prodrug?

Back 46

Just Tamiflu

Front 47

Whats the MoA of resistance to Oseltamivir and Zanamivir?

Back 47

Mutation in viral neuraminidase