Antiviral Drugs Flashcards Preview

Pharm Exam 2 > Antiviral Drugs > Flashcards

Flashcards in Antiviral Drugs Deck (76):
1

Antivirals are generally 

virostatic

2

Cross resistance example given with TK mutation

Idoxuridine and acyclovir

3

Three categories of agents that prevent entry

Attachment inhibitors

Coreceptor antagonists

Fusion inhibitors

4

Maraviroc MOA

CCR5 coreceptor antagonist

5

HIV1 can resist maraviroc by 

using drug-bound form of CCR5

This is called nonompetitive resistance 

6

Cenicriviroc MOA

dual CCR5 and CCR2 antagonist

7

Enfuvirtide MOA

inhibits gp41

 

(derived from natural gp41 HR2 sequence)

**does NOT have good oral BA

8

Inhibition of uncoating at the level of the endosomme/lysosome may be a good target because it...

takes place at a specific pH (low)

9

Arildone MOA

inhibits picornavirus uncoating

 

*inserts into a canyon in the VP1 viral protein and blocks ion transport

10

Plecoranil MOA

stops shedding of nucleocapsid proteins from RNA

11

First integrase inhibitor

Raltegravir

12

Second generation integrase strand transfer inhibitor (INSTI)

Dolutegravir

 

has a limited cross-resistance profile

13

Best class of AV drugs

Ones that act on replication of the genome

14

Because thymidine kinase is _____, nucleoside analogs can be administered in _______ form.

This provides what sort of advantage?

Viral TK is less specific

administered in unphosphorylated form

 

*Un-P drug enters cells more easily than phosphorylated ones

15

Nucleoside analog drugs generally cause ____

chain termination

16

Examples of nucleoside analogs

Idoxuridine

Ribavirin

Acyclovir/Gancyclovir

Azidothimidine

17

Two drugs that can interfere with mRNA transcription processing

Ribavirin

Interferon

18

Drugs that target proein translation

no specific inhibitors!

 

Interferon is non-specific for this

19

Post-trans modifications that can be targetss

glycosylation

phosphorylation

myristoylation

sialidation

20

Neuraminidase inhibitor drugs

Zanamavir

Oseltamavir

21

Neuraminidase function

"sialidase" = removes sialic acid from surface at level of glyccoproteins and glycolipids

 

22

Zanamavir MOA

inhibits NA of influenza A + B

23

Zanamavir requires

aersosol delivery

24

Oseltamavir is an analog of 

carbocyclic sialic acid

25

Other drug related to NA inhibitors

laninamivir

26

What is nirazoxamide?

a thiazolide

it might block glycosylation of viral hemagglutinin in the Golgi

27

Nitazoxanide is effective against

Yes

28

Protease inhibitors are all ____

 

Examples?

substrate analogs

 

Aquinavir, ritonavir, indinavir, lopinavir, tipranavir, darunavir

 

29

Protease inhibitors for HCV

Boceprevir and Telprevir

30

Amantadine is ___

lysosomotropic

31

Amantadine MOA

Inhibits viral RNA uncoating (A only)

also acts on maturation of influenza hemagglutinin glycoprotein = reduce infective potential

32

Rimantadine vs amantadine

3-4x greater activity

less toxic

33

Idoxuridine MOA

 

Uses?

 

Alternative drug?

Pyrimidine analog that inhibits viral DNA synthesis after activation by phosphorylation by TK

 

mainly for Herpes and Poxviruses, but has HIGH TOXICITY so isnt really used

 

Trifluridine = used topically for herpes keratitis + primary keratoconjunctivitis

34

Nuceoside analogs of cytosine and adenine

 

They require...

Cytarabine + Vidarabine

 

both have to be phosphorylated to be active

35

Ribivirin is a ___. 

Inhibits ________

triazole

inhibits 5' cap formation on mRNA

36

Ribavirin toxicity

dose-dependent HA

mutagen and teratogen

37

Acyclovir MOA

Purine analog that competes with dGTP

Two pronged effect:

  1. Binds to and inhibits Viral Polymerase
  2. Terminates the chain (doesn't have a 3' OH)

 

38

Acyclovir causes tissue irritation if _____

extravasation occurs when given IV

39

Acyclovir uses

Herpesviruses

(HSV, VZV, EBV, CMV)

40

What is valacyclovir?

 

Other related drugs?

Prodrug to acyclovir

(3-5x higher levels)

 

Famciclovir >> penciclovir

41

Gancyclovir MOA

Similar to acyclovir, but initial phosphorylation can be carried out by cellular enzymes

 

**selectivity is due to the fact that it is 30x higher affinity for viral enzymes

42

Gancyclovir major toxicity (tissue) and use?

Toxicity = rapidly dividing tissues

Use for AIDS-related CMV infections

43

AZT MOA

Chain terminator that is phosphorylated by cellular enzymes

( = can be used against viruses that dont bring own kinase)

 

Reverse transcriptase is more sensitive to AZT than host DNA pol, therefore it is targeted to infected cells

44

Mutants against AZT tend to have...

changes in RT

45

AZT AE's are mainly _____

hematologic

(granulocytopenia and anemia)

46

AZT commonly used with ____ for _____

Lamivudine (cytosine analog)

HIV

47

In addition to AZT, HIV treatment may involve _______ and ______

Dolutegravir (INSTI)

NRTI's Abacavir and Lamivudine

48

Lamivudine is very efficient againt 

HBV

49

Adefovir MOA and use

Toxicity?

Analog of adenosine monophosphate... competitively inhibits HBV DNA polymerase

 

Dose dependent nephrotoxicity

50

NNRTI MOA and recommended use

noncompetitive inhibitors that physically prevent RT from working

 

should NOT be used as monotherapy (d/t resistance)

 

51

5 NNRTIs

N/D/E

Etravirine, Rilpivirine

52

Drug that prevents HIV transmission to neonate

Neviripine

53

Drug used in HIV patients in combo with at least two active drugs

Etravirine

54

Competitive inhibitor of DNA polymerase that binds to pyrophosphate site

Foscarnet

 

also an inhibitor of RNA pol and HIV RT

 

Particularly potent to inhibit herpes DNApol

55

Foscarnet effective for ____

CMV retinitis

56

Protease inhibitors generally prevent ____

the maturation of viral particles

57

Protease inhibitors have been developed against...

the active site of aspartyl protease of HIV

 

This protein is NOT similar to any known host proteolytic enzyme

58

Saquinavir is the ____

least effective PI

59

PI that has ben shown to reduce death by 58%

Ritonavir

 

Used in combo therapy with other PI's

60

Amprenavir or fosamprenavir are generally used as ____

combo therapy

61

PI that has lower level of resistace

Darunavir

Approved for treatment-naive patients

62

Given with ritonavir for salvage option

Tipranavir

63

Benefit of Indinavir

Reduces HIV load (PCR can't even detect in 85% of patients)

64

Protease inhibitors for HCV

 

What do they target?

Telaprevir and boceprevir

 

target NS3.4A HCV serine protease

65

Target of Asunaprevir

NS5A inhibitor

66

Drug that targets the viral terminase complex

Letermovir

67

alpha and beta interferon mechanisms

  1. bind to specific receptors on adjacent cells and protect from viral infection
  2. enhance MHCI and MHCII on infected cells = enhance viral antigen presentation

68

What is truvada

emtricitabine/tenofovir disoproxil fumurate

Used fo preexposure prophylaxis

69

Adamantanes mechanism

M2 ion channel inhibitors

70

Gamma interferon secreted by ___ 

Function?

T cells

Enhances specific Tcell mediated immune response

71

general interferon functions (2)

Enhance specific immune response

Have direct antiviral effects (penetration, uncoating, degradation, inhibition of mRNA synthesis or methylation)

72

How do interferons interfere with protein synthesis?

Phosphorylating EIF-2

73

Single point mutation at different positions of M2 is sufficient to...

induce cross-resistance to amantadine and rimantadine

74

Oseltamavir vs Zanamavir - ages

Oselt = 1 yr. 

Zan = 7 for treatment, 5 for chemoprophylaxis

75

Sensitivity for RIDT's (rapid influenza diagnostic tests)

10-70%

76

Treatment vs lab confirmation of influenza

Treatment should NOT wait for lab confirmation of influenza