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Pharm Test 2 > Lecture 8 Antivirals > Flashcards

Lecture 8 Antivirals Flashcards

(67 cards)

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1
Q

What is the most severe constraint limiting the use of antivirals?

A

toxicity to the mammalian cell

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2
Q

Antivirals are said to have ____ ____ toxicity

A

poor selective

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3
Q

antivirals should interfere with a virus specific function that is either ____________ or _________

A

unique to the virus;

similar host function is much less susceptible to the drug

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4
Q

antivirals also can interfere with a _____ function necessary for viral _____

A

cellular; replication

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5
Q

Effective antiviral drugs have a therapeutic index of ___ to ___

A

100, 1000

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6
Q

All antivirals are viro___

A

static

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7
Q

2 examples of drugs that inhibit entry into host cells:

A

maraviroc; enfurvitide

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8
Q

____ is a CCR5 receptor antagonist

A

maraviroc

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9
Q

What is noncompetitive resistance and what drug is it especially associated with?

A

HIV uses drug bound form of CCR5 as the co-receptor; resistance in maraviroc

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10
Q

Maraviroc dosage should be modified when used with drugs that inhibit or stimulate

A

CYPA3

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11
Q

____ works by inhibiting the function of the gp41 transmembrane glyoprotein

A

enfuvirtide

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12
Q

Enfuvritide has low _____ _______, so it is mainly used for salvage therapy

A

oral availability

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13
Q

Viral uncounting is pH ____ in the endosomes/lysosomes but is pH _____ when fusing with the plasma membrane

A

dependent; independent

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14
Q

Example of drugs that inhibit viral uncoating:

A

amantidine and rimantidine

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15
Q

Raltegravir, dolutegravir, and elvitegravir work by inhibiting ______

A

integrase

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16
Q

Advantages of dolutegravir (2nd gen) or raltegravir):

  1. limited _______ profile
  2. prolonged serum ____
  3. minimal metabolization via ____, decreasing drug drug interactions
A

cross-resistance;
half-life;
CYP450

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17
Q

There is lesser risk of transmitting ____ ____ among individuals when using integrase inhibitors

A

drug resistance

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18
Q

Viral mutations leading to resistance against dolutegravir also diminish HIV ____ and ____ enzymatic activity

A

replication; integrase

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19
Q

Antivirals that inhibit polymerases are selective because:
1.
2.

A

virus uses its own enzyme to activate the drug;

viral polymerases are much more sensitive to drug than host

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20
Q

The fact that thydmidine kinase can phosphorylate the nucleoside analogs permits administration of the drug in a nonphosphorylated form that has what advantage over phosphorylated forms?

A

enters cell much more easily

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21
Q

2 examples of drugs that inhibit mRNA transcription and processing

A

ribavirin, interferon

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22
Q

____ nonspecifically inhibit protein translation

A

interferons

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23
Q

_____ helps the spread of influenza by removing scialic acid from the surface of infected cells so viruses can escape

A

neuraminidase (sialidase)

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24
Q

_____ is an inhibitor of viral neuraminidase

A

zanamivir

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25
____ blocks gycosylation of viral hemagglutinin in the golgi apparatus, preventing viral maturation
nitazoxanide--used in influenza
26
Amantadine/rimantadine are _____ blockers that inhibit __
M2 channel, uncoating
27
Amantadine is thought to inhibit ____ in the _____
acidifcation, golgi
28
Amantadine also acts on maturation of the influenza _____ glycoprotein, decreasing the ____ potential of virus progreny
HA; infective
29
_____ was the first liscensed antiviral, but was too toxic for systemic use due to lack of ____
Idoxuridine; specificity
30
Idoxuridine and trifluridine are used ____ to treat herpes ____ and primary _______
topically; keratitis; keratoconjunctivitis
31
Ribavirin is a ____ nucleoside analog that inhibits ____ formation on mRNA
purine; | 5' cap
32
Ribavirin is used to treat _____ as an aerosol and hepatitis ____; limited use due to toxicity
RSV; C
33
1st step of acyclovir activation:
phosphorylation by HSV thymidine kinase
34
Acyclovir is a ___ analog that competes with _____
guanosine, dGTP
35
Triphosphate acyclovir acts as a _____ because it does not have a ____ group
chain terminator; | 3' OH
36
____ toxicity may be seen with high doses of acyclovir
renal
37
After receiving its 2nd and 3rd P's from ____ enzymes, acyclovir binds to _____ and inhibits it
cellular | DNA polymerase
38
_____ has better _____ _____ than acyclovir because it is a prodrug
valacyclovir; oral bioavailability
39
____ is a monophosphate nucleoTIDE analog that is used to treat acyclovir resistant HSV
cidofovir
40
___ is a helicase primase inhibitor that is also used in treatment of HSV
pritelivir
41
Azidothymidine/zidovudine (AZT) is a ______
nucleoside reverse transcriptase inhibitor
42
AZT must be _____ to become active. It binds ______, aka reverse transcriptase
phosphoryalted; RNA dependent DNA polymerase
43
Side effects of AZT: ______ surpression, _____ disturbances.
bone marrow; GI
44
There is an increased risk of side effects with AZT if used with drugs that interact with the _______ pathway such as _____
glucuronyl transferase; aspirin/acetaminophen
45
Lamivudine is a ___ analog and is a _____
cytosine; NRTI
46
What else does lamivudine treat?
Hep B
47
_____ is a nucleTide reverse transcripase inhibitor used to treat HIV
tenofovir
48
sofosbuvir is used in ____ treatment by interfering with the _____ ____
Hep C; NS5B RNA polymerase
49
NNRTIs such as efravirenz work by ______ inhibting RT. ___ develops rapidly
physically; resistance
50
Dasabuvir (NNRTI) is used in treatment of _____ by acting as an analog of _______
Hep C; nonstructural NS5B
51
Favipiravir is used in treatment of _____ and inhibits the viral ______
influenza A and B; polymerase heterotrimer
52
Favipiravir is a ____ analogue that inhibits viral polymerase _____. It has a high barrier for _____
nucleobase; PB1; drug resistance
53
Protease inhibitors end in _____
navir
54
Protease inhibitors bind to the active site of _____ protease of HIV
aspartyl
55
_____ is used to increase the efficiency of other protease inhibitors of HIV
ritonavir
56
____ is given with ritonavir as a salvage option for patients with resistance to other protease inhibitors
tipranavir
57
____ and ____ are examples of direct acting antivirals that treat HEP c
telaprevir, bocepravir
58
Telaprevir and bocepravir target _____ in treatment of HCV
NS3/4A non structural protein
59
HCV drugs are beginning to focus on Direct acting antivirals that permit increased sustained virologic ____, _____, and shortened ______ of treatment
response, tolerability, duration
60
_____ is an example of an inhibitor of viral complexes
daclatasvir
61
Daclatasvir treats ____ by inhibiting ______ protein
HCV, NS5A nonstructural
62
inhibitors of ____ end in asvir
viral complexes
63
New directions for antivirals include: 1. targeting the viral _____ complex (ie CMV), 2. targeting virus-host interaction, 3. iSAVE-based gene therapeutics that use genetically modifed host ____ 4. baseline ____ testing 5. taking into account _____ genotypes
terminase; T-Cells; resistance; viral
64
alpha and beta interferons prevent viral infection of noninfected cells by binding to _____ _____; also enhance expression of _____
surface receptors; MHC
65
_____ interferon enhances the specific T cell mediated immune response
gamma
66
Why were interferons hoped to be so effective?
act at several levels of the viral cycle
67
What is an example of Pre-exposure prophylaxis for HIV?
Truvada (emtricitabine/tenofovir disoproxil fumarate)

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