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Flashcards in Antimicrobial Agents- Antivirals Deck (56):
1

An ideal antiviral would target all major pathogenic viruses by doing either what to things? do these exist?

1. either targeting a highly conserved viral target or targeting a cellular protein that is critical for virus replication
2. no

2

Review the following common viral targets?

attachment
uncoating
viral mRNA synthesis
translation viral mRNA
replication viral genome
maturation virus particle
budding, release new virus

3

What is the goal of antivirals against HIV?

reduce virus loads as low as possible, increase CD4 T cells counts

4

How does maraviroc act?

small molecule inhibitor- binds CCR5 allosterically preventing HIV gp120/CCR5

5

Does maraviroc enhance CD4 T cell counts even in individuals who carry CXCR4- utilizing HIV? how does resistance set in?

1. Yes
2. changes in HIV gp120

6

How does enfuvirtide work? what is the problem with this?

1. C peptide mimic that binds N peptide on HIV gp41- preventing fusion
2. expensive to synthesize and causes local inflammation

7

What are the two different kinds of RT inhibitors?

1. competitive substrates for nucleosides/tides
2. small molecule inhibitor of RT activity

8

How do NRTIs work…what do they lack?

analog- lacking 3 hydroxyl group causing DNA chain termination

9

All NRTIs require what?

phosphorylation by cellular enzymes to the triphosphate form

10

What is the difference between NRTIs and NtRTIs?

NtRTIs have one phosphate group on the pro-drug

11

What makes NRTIs and NtTRIs so effective? how does virus gain resistance?

1. cellular polymerases have proof reading activity whereas HIV does not
2. increased ability to exclude NTRI or remove the analog

12

What are the 3 NRTIs we need to know?

abacavir
emtricitabine
lamivudine

13

Which NRTI is a guanosine analog and not a cytosine analog?

abacavir

14

What is the one NtRTI we need to know? what is a major side effect issue with this drug

tenofovir
competes with other drugs for kidney tubule secretion

15

Do we often find combinations of NtRTIs and NRTIs?

Yes

16

How do non-nucleoside RT inhibitors (small molecule inhibitors) work?

1. binds to an allosteric site on RT, hydrophobic pocket near catalytic domain- decreases mobility of RT--> inhibits polymerase

17

Do non-nucleoside and nucleoside RT inhibitors use the same domain?

No- distinctly different domains are responsible for the antiviral activity

18

What are the 2NNRTIs?

neverapine
efavirenz

19

What is dolutegravir?

Integrase inhibitor

20

T-F--integrase inhibitors work by joining viral 5'DNA ends?

False- 3'

21

HIV protease inhibitors block what? how?

1. blocks the maturation of the virus particle
2. derived from natural peptidic substrates of HIV-1 protease and bind active site

22

What are the side effects of ritonavir/ saquinavir - protease inhibitor?

lipodystrophy-central adipose tissue

[numerous effects supposedly, but that's the only one listed]

23

What are 2 protease inhibitors?

ritonavir (blocks 3A4)
saquinavir

[mentions atazanair in the lecture but not on the drug sheet]

24

HAART regimens usually include 3 drugs---what are they in general terms?

usually 2 nucleoside RT inhibitors and either a protease inhibitor or a non-nucleoside RTI or an integrate inhibitor

25

What can antivirals for HIV also be used for? which one has been most successful?

microbicides, post exposure prophylaxis, maternal-fetal transmission

tenofovir for microbocide

26

Ganciclovir can be used for what 2 herpes?

EBV, CMV

27

Foscarnet can be used for which herpes viruses? 4

CMV, EBC, VZV, HSV 1 &2

28

Famciclovir, valacyclovir and acyclovir are used for what herpes?

HSV and VZV

29

What is acyclovir and valacyclovir activated by? how do they work?

1. viral nucleoside kinase
2. incorporate in elongation of DNA and terminate production of new genome

30

When do we use acyclovir and valacyclovir for prophylaxis?

BMT and organ transplant

31

Between acyclovir and valacyclovir, which one provides more sustained and higher levels in the blood?

valacyclovir

32

The whole family of HSV inhibitors elevate what?

HIV NRTIs---amounts should be adjusted.

33

T-F--famciclovir is an acyclic guanine derivative has a different mose of action do to 3' OH group?

true- still cause chain termination

34

T-F--cidofovir is an acyclic nucleoside phosphonate derivative of adenine?

False- cytosine

35

What is cidovir activated by?

cellular kinases and thus does not need virus encoded TK- MAINTAIN ACTIVITY FOR STRAINS WITHOUT TK

36

Is cidofovir a competitive inhibitor of the viral DNA polymerase or a chain terminator?

mainly a polymerase inhibitor, but can act as a chain terminator

37

How does foscarnet work?

binds directly to pyrophosphate binding sites of HSV DNA polymerase--NONCOMPETITIVE (100x more that host cells)

38

Docosanol is what?

A saturated fatty alcohol that is approved as a topical cream

39

Usually we use ganciclovir IV for CMV severe cases. It is more effective for HSV and VZV, but why don't we use it?

It is toxic--> granulocytopenia and thrombocytopenia

40

What is fomivirsen-

antisense RNA against CMV that can be used against CMV retinitis in immunocompromised individuals

41

What is amantadine and rimantadine?

Influenza viral uncoating inhibitor

42

What is zanamivir and oseltamivir?

influenza neuraminidase inhibitor

43

How does amantadine work?

binds M2 blocks acidification--Influenza A only

44

Does amantadine need to be used quickly?

yes within 48 hours of first symptoms

45

T-F--most circulating influenza strains are resistant to amantadine? what else is it used for?

Yes
anti-parkinson

46

Palivizumab is used to treat who?

infants under 2 with cardiac or pulmonary disease prophylactically for RSV

47

Hospitalized acutely ill infants with RSV are treated with what?

ribavirin- nucleoside analog

48

In what ways does ribavirin work? 3

1- inhibit inosine monophosphate dehydrogenase depleting guanosine triphosphate
2- base pair with cytidine or uridine--> mutations
3- shifts CD4 T cells from Th2 to Th1

49

Combination therapy with nucleoside RT inhibitors and what is best for Hep B?

IFN-a

50

lamivudine is what?

specific HBV nucleoside analogue reverse transcriptase inhibitor

51

What is simeprevir?

HepC protease inhibiotr

52

What is sofosbubir?

Hep C nucleoside inhibitor

53

What is a flavivirus, plus strand, that infects about 3% of the world

Hep C

54

What is wrong with ribavirin and interfering alpha 2a treatment for chronic hep C?

50% of US cases are resistant-- [ribavirin is oral and INFa is injected.]

55

What do we use simeprevir with?

ribavirin and IFNalpha 2a

56

T-F--combo treatments of protease inhibitors and polymerase treatments + ribavirin are effective with close to 50% clearance of chronic Hep C?

False- near 100%