Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Block G -- Infection > Dr. Papenburg -- Antiviral Agents > Flashcards

Dr. Papenburg -- Antiviral Agents Flashcards

1
Q

4 virus-specific events that antiviral agents must ideally inhibit

A
  • Block viral entry into the cell
  • Block viral exit from the cell
  • Be active inside the host cell
  • Exert some sort of immunomodulatory effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How a therpeutic agent’s antiviral effect is measured

A

By its ability to *inhibit *viral replication (50% Inhibitory Concentration)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

6 stages of viral replication

A
  1. Attachment
  2. Entry
  3. Uncoating
  4. Synthesis
    1. Early proteins
    2. Nucleic acids
    3. Late proteins
  5. Assemply
  6. Release
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

2 classes of antivirals against influenza

A
  • Adamantanes (M2 ion channel inhibitors)
  • Neuraminidase inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

2 adamantanes

A
  • Amantadine
  • Rimantidine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

2 neuraminidase inhibitors

A
  • Oseltamivir (Tamiflu)
  • Zanamivir (Relenza)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Amantadine function

A

Disable M2 protein –> prevent viral uncoating –> virus rendered inert

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Neuraminidase inhibitor function

A

Inhibit release of virions and promote clumping

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Target stage of Adamantanes

A

Uncoating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Target stage of neuraminidase inhibitors

A

Release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Flu type covered by adamantanes

A

Influenza A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Flu types covered by NAIs

A

A and B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Administration of adamantanes

A

Oral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Administration of NAIs

A

Zanamivir = Inhaled

Oseltamivir = Oral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Age range for adamantanes

A

> 1 year old

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Age range for NAIs

A

Zanamivir = > or = 7 yo

Oseltamivir = all ages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

4 side effects of adamantanes

A
  • Nausea
  • Dizziness
  • Insomnia
  • Anxiety
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Side effects of NAIs

A

Zanamivir = Bronchospasm

Oseltamivir = GI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Signs of resistance against treatment with adamantanes

A

Persistent or recurrent fever in children

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Type of mutation involved in resistance to adamantanes

A

Single point mutation of the M2 protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Effect of mutation for adamantane resistance on viral replication, transmission and virulence

A

No impairment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Effect of mutations for NI resistance on replication, infectivity and virulence

A

Decreased

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Major problem with adamantanes

A

Rapid emergence of resistance during treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

5 benefits of oseltamivir therapy

A

Reduction of:

  1. Duration of illness in adults and children
  2. Viral shedding and viral load
  3. Antibiotic use
  4. Length of hospitalization
  5. Mortality in hospital
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
4 types of people to treat for influenza
Prompt empiric treatment recommended for persons with suspected or confirmed influenza AND: * Illness requiring hospitalization * Progressive, severe, or complicated illness * At risk for severe disease * Essential healthcare workers
26
7 types of patients who are an increased risk for complications
1. Chronic medical conditions 2. Living in a nursing home or long-term care center 3. Age 65 years and over 4. Pregnant women, especially in T2 and T3 * Also post-partum 2 - 4 weeks 5. Healthy children \<24 months * If severe or progressive disease 6. Neurological/nerudevelopmental disorders 7. Severe obesity = BMI \>40
27
4 alternatives to oseltamivir
* Zanamivir (if tolerated) * IV zanamivir (special access) * IV peramivir (investigational; only in emergency) * Combination Tamiflu + Amantidine
28
How many types of herpesviruses are there? Name most of them
8 types: 1. HSV-1 2. HSV-2 3. VZV 4. CMV 5. EBV 6. HHV-6 7. HHV-8
29
Acyclovir activity for herpesvirus
* HSV * VZV (lower affinity) * Very poor activity against others
30
Acyclovir bioavailability po
15 - 30%
31
Metabolism of acycolvir (ACV)
1. Phosphorylated to monophosphate form by **viral** thymidine kinase (TK) 2. Di- and tri-phosphrylated by **host** cellular enzymes
32
Antivirally active form of ACV
Triphosphate form
33
Triphosphate ACV function
Inhibit viral DNA synthesis by: 1. Competing with dGTP for viral DNA polymerase 2. Chain termination
34
Most common reason for ACV resistance in HSV
Virus deficient in TK NOTE: rarely due to altered TK or DNA pool; rare in immunocompetent
35
Most common reason for ACV resistance in VZV
Altered TK (lower affinity for ACV)
36
3 PO uses of ACV
1. Genital herpes * Primary infection * Suppression of recurrences 2. Oro-labial herpes * Primary * ± Recurrence 3. Primary VZV
37
Topical ACV use
Keratoconjunctivitis
38
5 IV uses of ACV
1. HSV encephalitis 2. Neonatal HSV 3. HSV in immunocompromised 4. VZV (primary or reactivation) in immunocompromised 5. Prophylaxis post bone marrow transplant
39
2 potential side effects of ACV
Generall well tolerated, but may have: 1. Nephrotoxicity when given IV 2. Neurotoxicity in renal failure
40
Define valacyclovir
Pro-drug of acyclovir
41
Method of administration of valacyclovir and its bioavailability
PO --\> 70%
42
Describe the resistance profile of penciclovir/famciclovir
* Able to overcome some resistance to acyclovir * TK deficient mutants remain resistant * Rare in immunocompetent
43
3 clinical indications for famciclovir
1. Genital herpes * Primary * Recurrence * Suppression 2. Oro-labial HSV 3. VZV * Primary * Zoster
44
Gancyclovir activity
In vitro = all herpesviruses NOTE: 100x more active against CMV than ACV
45
Method of administration of gancyclovir
IV via central venous line
46
Gancyclovir mechanism in CMV infected cells
1. Virally-encoded UL97 phosphotransferase performs first phosphorylation 2. After di and tri-phosphorylation cellular enzymes), GCV inhibits viral DNA pol
47
Most common cause of GCV resistance in CMV
Mutations in the UL97 gene NOTE: DNA pol (UL54) mutations are rare. DOuble mutants (UL97 AND UL54) = most resistant
48
Cross-resistance of GCV in event of UL54 mutation
Cidofovir and foscarnet
49
4 clinical indications for GCV
1. CMV retinitis 2. CMV pneumonitis 3. Prophylactic or pre-emptive * Bone marrow transplant (D-/R+) * Solid organ transplant (D+/R-) 4. Congenital CMV
50
Combo treatment for CMV pneumonitis
GCV + anti-CMV immunoglobulin
51
4 GCV side effects
1. Requirement of central line 2. Bone marrow toxicity * Neutropenia (40%) * Thrombocytopenia (15 - 20%) 3. CNS manifestations (5%) 4. Teratogenic
52
Define valgancyclovir
Oral pro-drug of gancyclovir with 60% bioavailability
53
2 indications for valgancyclovir
1. Treat and suppress CMV retinitis 2. CMV prophylaxis in solid organ transplant
54
In vitro activity of cidofovir (4)
1. Herpesviruses 2. Adenoviruses 3. Papillomaviruses 4. Polyomaviruses
55
In vivo activity of cidofovir (2)
* CMV resistant to GCV (UL97) * TK-deficient HASV/VZV
56
Antiviral that does not depend on viral enzymes for phosphorylation
Cidofovir
57
Clinical indications for cidofovir
CMV disease in * Immunosuppressed patients who do not tolerate FCV and foscarnet * Whose virus is suspected to be resistant to GCV and foscarnet
58
3 side effects of cidofovir
1. Dose-dependent nephrotoxicity 2. Neutropenia 3. Potentially carcinogenic and teratogenic
59
Foscarnet activity
* All herpesviruses * CMV resistant to GCV (UL97) * TK deficient HSV/VZV
60
Admniistration of foscarnet
IV
61
Antiviral that does not require any phosphorylation
Foscarnet (direct inhibition of DNA pol)
62
Clinical indication of foscarnet
CMV disease in immunosuppressed patients who do not tolerate GCV or whose virus is suspected to be resistant to GCV
63
2 side effects of foscarnet
* Nephrotoxicity * Electrolyte abnormalities (calcium, phosphate, potassium)
64
3 types of anti-hepatitis agents
1. Interferon-alpha 2. Ribavirin 3. Nucleoside/nucleotide analogues
65
Type of hepatitis covered by IFN-alpha
* HBV * HCV
66
Type of hepatitis covered by ribavirin
HCV
67
Type of hepatitis covered by nucleoside/nucleotide analogues
HBV
68
5 nucleoside/nucleotide analogues to treat hepatitis
1. Lamivudine 2. Adefovir 3. Telbivudine 4. Tenofovir 5. Entecavir
69
Mechanism of action of IFN-alpha
No direct antiviral effect, but antiviral activity occurs via activation of host cells to produce a series of antiviral proteins
70
Method of admnistration of IFN-alpha
IM or subcutaneous injection
71
What allows once weekly dosing of IFN-alpha
Attachment of large, inert polyethylene glycol (PEG) molecules
72
5 side effects of IFN -alpha
1. Flu-like syndrome 2. Myelosuppression 3. Neurotoxicity 4. Autoimmune disorders (thyroiditis) 5. Cardiovascular effects
73
3 clinical indications of IFN-alpha
1. Chronic HBV 2. Acute and chronic HCV 3. Refractory codylomata accuminata (intralesional)
74
Mechanism of action of ribavirin
1. Phosphorylation by host cell enzymes 2. Mono and tri-phosphorylated forms inhibit synthesis of GTP
75
3 clinical indications of ribavirin
1. Chronic HCV (po) 2. RSV, parainfluenza virus (inhaled + or - IV) * In severely immunocompromised 3. Arenavirus hemorrhagic fevers
76
2 side effects of ribavirin
1. Dose-related reversible anemia 2. Teratogenic
77
Administration of nucleoside/nucleotide inhibitors in chronic Hep B infection
Oral
78
Mechanism of nucleoside/nucleotide inhibitors in chronic Hep B infection
1. Require phosphorylation 2. Inhibit HBV DNA-pol / reverse transcriptase
79
2 viruses with emergent resistance towards nucleoside/nucleotide inhibitors
HBV and HIV
80
Indication for nucleotide/nucleoside inhibitors
Chronic HBV
81
Antiviral that is a general purine nucleoside analog
Ribavirin
82
Pyrophosphate analog
Foscarnet
83
Cytidine analog
Cidofovir
84
3 guanosine analogs
1. Acyclovir 2. Penciclovir 3. Gancyclovir
85
3 antivirals that are prodrugs and the active drug with which they are associated
1. Vancyclovir (acyclovir) 2. Famiciclovir (penciclovir) 3. Valgancyclovir (gancyclovir)

Block G -- Infection (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions