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Infectious Disease > Antivirals > Flashcards

Antivirals Flashcards

1
Q

What is rimantadine used to treat?

A

influenza A

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2
Q

What is the mechanism of action of rimantadine?

A

it blocks the M2 proton channel and prevents viral uncoating

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3
Q

How and when is rimantadine given?

A

orally within the first 48 hours of exposure

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4
Q

What is oseltamivir used to treat?

A

influenza

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5
Q

Oseltamivir is also known as what?

A

tamiflu

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6
Q

What is the mechanism of action of oseltamivir?

A

it blocks neuraminidase

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7
Q

What is special about the pharmacokinetics of oseltamivir?

A

it is given as a prodrug that must be activated in the gut and liver

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8
Q

What is zanamivir used to treat?

A

influenza A and B

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9
Q

What is the mechanism of action of zanamivir?

A

it blocks neuraminidase

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10
Q

How and when is zanamivir administered?

A

oral inhalation within the first two days of infection

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11
Q

What is the major adverse effect associated with zanamivir?

A

it may cause bronchospasm in asthmatics

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12
Q

List the three important anti-influenza medications.

A
  • rimantidine
  • oseltamivir
  • zanamivir
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13
Q

What is the mechanism of action of ribavirin?

A

it is an anti-metabolite that blocks GTP formation, inhibits viral mRNA capping, and inhibits viral RNA-dependent polymerase

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14
Q

What is responsible for the selectivity of ribavirin?

A
  • it has no kinase selectivity

- it has a selectivity for viral polymerase

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15
Q

What are the indications for ribavirin?

A
  • orally and with INFa for HepC

- as an aerosol for respiratory syncytial virus

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16
Q

What are the adverse effects of ribavirin?

A
  • known teratogen and embryotoxin

- may cause a dose-dependent anemia

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17
Q

What is the mechanism of action of acyclovir?

A

it is a guanosine analog and chain terminator which inhibits viral genome replication

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18
Q

What is responsible for the selectivity of acyclovir?

A

viral kinase and polymerase specificity

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19
Q

Which viruses are resistant to acyclovir?

A

those that are without thymidine kinase

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20
Q

What is acyclovir used to treat?

A

HSV-1 and HSV-2

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21
Q

What is the mechanism of action of ganciclovir?

A

it is a guanosine analog anti-metabolite which inhibits viral genome replication

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22
Q

How does the selectivity of ganciclovir compare to that of acyclovir?

A

it is less kinase and polymerase specific than acyclovir

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23
Q

What is ganciclovir used to treat?

A

retinitis and visceral effects of CMV

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24
Q

What are the side effects of ganciclovir?

A

due to reduced selectivity compared to acyclovir

  • teratogenic
  • myelosuppressive
  • neuropathic
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25
How well tolerated is acyclovir?
very well given its high selectivity
26
What is the mechanism of action of foscarnet?
it is a pyrophosphate anti-metabolite which directly inhibits viral polymerase to prevent viral genome replication
27
What is foscarnet used to treat?
- synergistic with ganciclovir for CMV | - used for valcyclovir-resistant herpes simplex
28
What is the primary adverse effect of foscarnet and how do we deal with it?
it is potentially nephrotoxic, so use a saline preload
29
What is the mechanism of action of cidofovir?
it is a cytosine anti-metabolite
30
Describe the selectivity of cidofovir?
it has no kinase specificity, just polymerase specificity
31
What is cidofovir used to treat?
herpes simplex and CMV
32
How is cidofovir cleared from the body?
active tubular secretion
33
Cidofovir is usually given alongside what other drug?
probenecid to increase bioavailability
34
Cidofovir has what adverse effect?
dose-dependent nephrotoxicity
35
What is the mechanism of action of trifluridine.
it competes with TTP for viral polymerase
36
Describe the selectivity of trifluridine.
it has very low specificity, activated by hosts kinases and low polymerase specificity
37
How is trifluridine used?
- limited selectivity restricts it to topical use | - best for HSV conjunctivitis or epithelial keratitis
38
List five drugs used to treat herpes by inhibiting viral genome replication.
- acyclovir - ganciclovir - foscarnet - cidofovir - trifluridine
39
List five drugs used to treat hepatitis.
- interferon alpha - lamivudine - telaprevir - simeprevir - sofosbuvir
40
What drug combination is used for HCV eradication?
12-24 week course of - interferon alpha - ribavirin - sofosbuvir
41
What is interferon-alpha used to treat?
- HBV management | - HCV eradication (with ribavirin)
42
How is the bioavailability of interferon-alpha improved?
using a pegylated formulation
43
What are the adverse effects of interferon alpha?
- may induce autoantibodies | - flu-like syndrome
44
What is the mechanism of action of lamivudine?
it is a cytosine analog that inhibits HIV RT and HBV DNA polymerase
45
Lamivudine is used in the treatment of which two conditions?
HBV and HIV management
46
What benefit does lamivudine offer to those with HBV?
- management of their infection | - reduced risk of HCC
47
What is emtricitabine?
a fluorinated form of lamivudine
48
What hepatitis treatment is recommended for pregnant women?
lamivudine
49
What is the mechanism of action of telaprevir?
it is an HCV protease inhibitor
50
How is the effect of telaprevir enhanced?
by taking it with a fatty meal
51
How is telaprevir metabolized?
via CYP3A4 and Pgp
52
What is the mechanism of action of simeprevir?
it is an HCV protease inhibitor like telaprevir
53
What polymorphisms affects the effect of simeprevir?
Asians have 3x higher bioavailability
54
What are the two adverse effects of simeprevir?
- photosensitivity rash | - sulfa moiety that causes Steven-Johnson syndrome
55
What is the mechanism of action of sofosbuvir?
it inhibits HCV RNA polymerase
56
Anti-HIV agents fall into what six categories?
- binding inhibitors - fusion inhibitors - integrase inhibitors - nucleoside RT inhibitors - non-nucleoside RT inhibitors - protease inhibitors
57
What is the mechanism of action of maraviroc?
it is an HIV binding inhibitor that interferes with the gp120-CCR5 interaction
58
How does HIV become maraviroc-resistant?
it takes on a CXCR4 tropism or the host has a CCR5 mutation
59
What are the adverse effects of maraviroc?
- hepatotoxicity preceded by an allergic reaction | - cough, myalgia, diarrhea
60
What is the mechanism of action of enfuvirtide?
it binds gp41 and serves as a fusion inhibitor
61
Why is enfuvirtide rarely used?
because it causes an injection site reaction in most patients and has a half life of only 4 hours, so it requires lots of injections
62
Which five nucleoside RT inhibitors are effective against HIV?
- zidovudine - lamivudine - emtricitabine - abacavir - tenofovir
63
What is the mechanism of action of zidovudine?
- a thymidine analog and chain terminator | - nucleoside RT inhibitor
64
Nucleoside reverse transcriptase inhibitors inhibit what aspect of HIV infection?
they inhibit stable infection of new cells
65
How is zidovudine used clinically?
it's short half life limits it to use with lamivudine to reduce mother-to-newborn transmission
66
How does resistance to zidovudine develop?
through RT mutations
67
What is the mechanism of action of abacavir?
it is a guanosine analog and NRTI
68
How is abacavir metabolized?
by alcohol dehydrogenase
69
What is the most significant adverse effect of abacavir?
a severe hypersensitivity reaction predicted by HLA-B5701
70
What is the mechanism of action for tenofovir?
it is a chain terminating NRTI
71
Describe the selectivity of tenofovir.
it has limited selectivity because it is a monophosphate and therefore has no kinase specificity
72
Tenofovir is part of what HIV regimen?
PReP
73
What are the two forms of tenofovir?
- alafenamide | - disoproxil
74
What is alafenamide?
a form of tenofovir with less renal toxicity and bone loss
75
What is the mechanism of action of raltegravir?
it is an HIV integrase inhibitor
76
What are the disadvantages of raltegravir?
- resistance develops quickly | - can't take with cations or other buffered drugs
77
What is the mechanism of action of dolutegravir?
it is an HIV integrase inhibitor
78
What are the benefits of dolutegravir over other HIV integrase inhibitors?
resistance develops more slowly and there is less hepatotoxicity
79
What is the mechanism of action for nevirapine?
it is a non-competitive inhibitor of HIV RT
80
How is nevirapine used in clinic?
as a single dose therapy to prevent transmission during childbirth
81
What are the disadvantages of nevirapine?
- inducer of CYP3A4 - resistance emerges quickly - causes a skin rash
82
What is the mechanism of action of efavirenz?
it is a NNRTI for HIV
83
Many HIV drugs have what adverse side effect?
they induce and/or inhibit CYP3A4
84
What is the mechanism of efavirenz?
it is an HIV NNRTI
85
How is efavirenz taken to increase bioavailability?
take it on an empty stomach
86
What is the adverse effect of efavirenz?
although it has little CNS penetration, it is highly toxic there, causing dizziness, drowsiness, nightmares, and amnesia
87
What is the mechanism of action of indinavir?
it is an HIV protease inhibitor
88
What are the adverse effects of indinavir?
it causes hyperbilirubinemia and nephrolithiasis
89
What is the mechanism of action of darunavir?
it is an HIV protease inhibitor
90
Most protease inhibitors are associated with which adverse effects?
lipodystrophy and metabolic syndrome
91
What is the advantage of using darunavir?
it continues to work after HIV becomes resistant to other PIs
92
What are the adverse effects of darunavir?
lipodystrophy and metabolic syndrome
93
Darunavir is often given alongside what other drug?
cobistat
94
What is the mechanism of atazanavir?
it is an HIV protease inhibitor
95
What is the advantage of using atazanavir compared to other HIV PIs?
it has no associated lipodystrophy or metabolic syndrome
96
What is cobicistat?
a CYP3A4 inhibitor used to extend the bioavailability of HIV protease inhibitors
97
Cobicistat increases the activity of HIV protease inhibitors in what two ways?
- it increases absorption by inhibiting intestinal efflux transporters - it inhibits CYP3A4
98
When is cobicistat contraindicated?
when patients have a GFR less than 30
99
Name two CYP3A4 inhibitors used to enhance the bioavailability of HIV protease inhibitors.
- cobicistat | - ritonavir

Infectious Disease (9 decks)

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