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Anti-Infectives Exam 3 > Lecture 2 - Antiviral Agent 1 > Flashcards

Lecture 2 - Antiviral Agent 1 Flashcards

1
Q

Neuraminidase inhibitors

A

Oseltamivir
Zanamivir
Peramivir

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2
Q

Cap dependent endonuclease inhibitor

A

Baloxavir

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3
Q

Neuraminidase Inhibitors MOA

A

Block neuraminidase interfering with the release of replicated influenza virus from infected host cells

Best efficacy if admin w/in 12hrs of symptoms

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4
Q

What does Neuraminidase enzyme do

A

Cleaves cellular-receptor silica acid allowing replicated virus to exit

cleaves silica acid on the mucin in airway epithelium facilitating upper airway invasion

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5
Q

Oseltamivir Dosing & Dose adjustment

A

5 days = treatment
10 days = Prophylaxis

Req renal dose adjustment due to renal clearing

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6
Q

Route of admin for Neuraminidase inhibitors

A 
Oseltamivir = PO
Zanamivir = INH
Peramivir = IV
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7
Q

CI Oseltamivir

A

Severe renal and hepatic impairment

** can use in Pregnancy **

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8
Q

DI Oseltamivir

A

Probenecid inhibit renal elim = inc conc

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9
Q

Oseltamivir ADE

A

Mostly GI, take with food

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10
Q

Zanamivir Dosing

A 
Treatment = 5 days
Prophylaxis = 10 days
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11
Q

DI + Dose adjustment Zanamivir

A

None, v little renal clearance ~ 10%

Also class C greg = can use

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12
Q

CI Zanamivir

A

Asthma, COPD (give albuterol before giving drug)

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13
Q

Zanamivir ADE

A

Cough

Btonchospasm

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14
Q

Peramivir dosing

A

5 days = treatment only

no prophylaxis dose

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15
Q

Peramivir Dose adjustment

A

Yes, renal cleared

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16
Q

DI Peramivir

A

none

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17
Q

Peramivir ADE

A

D,N,V

some CNS

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18
Q

Baloxavir (cap endonuclease inhibitor) MOA

A

inhibition of Cap-dependent endonuclease lends to interruption of viral RNA transcription

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19
Q

Baloxavir Dosing & Adjustment

A

1 tab both treatment & Prophylaxis, give within 48hrs of symptom

no adjustment, just for weight

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20
Q

Baloxavir DI

A

Dont co-admin with polyvalent cations = chelate

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21
Q

Baloxavir ADE

A

D,N,V

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22
Q

Remdesivir MOA

A

Binds nd inhibits viral RNA-dependent RNA polymerase activity

Its an adenosine analog thats FDA approved

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23
Q

Remdesivir Dosing adjustment

A

no renal or hepatic

given IV

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24
Q

Remdesivir CI

A

Hepatic insufficiency

renal dysfunction

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25
Q

Remdesivir ADE

A

Rash
Nephrotoxicity
hepatic toxicity

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26
Q

Remdesivir DI

A

Hepatic enzyme + P-GP inducers not recommended due to potential decrease in remdesivir drug conc

ie. Rifamycins, Carbamazepine, Phenobarbital, Efavirenz, Nevirapine, Rilpivirine

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27
Q

Dexamethasone MOA

A

Binding to Pro/3CLpro (viral protease), inhibition of neutrophil apoptosis/demargination, promotion of anti-inflammatory genes (IL-10)

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28
Q

Dexamethasone dose adjustment

A

Nah

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29
Q

Dexamethasone CI

A

Current MTB, HSV

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30
Q

Dexamethasone DI

A

moderate CYP450, 3A4 inducer

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31
Q

Dexamethasone ADE

A

Reactivation of HBV, HSV, TB, dysglycemias, CNS changes

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32
Q

Tocilizumab MOA

A

Monoclonal antibody to IL-6 receptor, treats cytokine release syndrome

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33
Q

Tocilizumab Dosing adjustments

A

None

IV only, given once

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34
Q

Tocilizumab CI & DI

A

Dont give in ppl with low BC

Dont give with immunosuppressants

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35
Q

Tocilizumab ADE

A 
HSV/VZV reactivation
Opportunistic infections**
TB
Thrombosis**
GI perforation
Hypersensitivity
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36
Q

Baracitinib MOA

A

inhibit clatkhrin-mediated endocytosis and thereby inhibit viral entry, modulates hematopoiesis and immune cell function

JAK1 inhib

37
Q

Baracitinib Dose adjustments + clearance

A

50% w/ renal dysfunction = 2mg

75% renal clearance

38
Q

Baracitinib DI

A

Probenecid dec clearance

Azathiorine and cyclosporine inc cytopenias

39
Q

Baracitinib ADE

A 
Cytopenias**
Opportunistic infections**
Thrombosis**
Hepatotoxicity
Dyslipidemia
Malignancy
HSV,VSV reactivation
40
Q

Nirmatrelvir w/ ritonavir (Paxlovid)

A

Protease inhibitor w/ booster

Nirmatrelvir: 3CLpro or nsp5 protease inhibitor

Ritonavir: CYP450 enzyme inhibitor (acts as booster)

41
Q

Paxlovid renal dose adjustment

A

50% with renal dysfunction

42
Q

Paxlovid CI

A

Severe renal dysfunction

43
Q

Paxlovid DI

A

Potent CYP3A4 inhib

44
Q

Paxlovid ADE

A

Mostly GI
Dysguesia = impaired taste
Rebound phenomena

45
Q

Enzyme inducers that reduce lvls of Paxlovid

A 
Rifampin
Rifabutin
Phenytoin
Phenobarbital 
Carbamazepine
46
Q

Enzyme inhibitors that increase lvls of Paxlovid

A 
Itraconazole
Voriconazole
Fluconazole
Posaconazole
Isavuconazonium
Clarithromycin
47
Q

Molnupiravir MOA

A

Active metabolite works via viral error catastrophe, also referred to as viral lethal mutagenesis.

NHC-TP incorporation into viral RNA by viral RNA-dependent RNA polymerase, results in accumulation of errors in viral genome leading to inhibitor of replication

** Mutagen + toxic metabolite **

48
Q

Molnupiravir Dose adjustments

A

none

49
Q

Molnupiravir DI

A

none significant

50
Q

Molnupirvir CI

A

Pregnancy

Child bearing age not on barrier contraception

51
Q

Molnupirvir ADE

A

Teratogenicity
Cartilage + bone growth abnormalities < 18yrs old
D + N

52
Q

Drugs of choice for mild-moderate ovid

A

Remdesivir
Paxlovid
Bebtelovimab

53
Q

Drug used for PrEP?

A

Evusheld (Tixagevimab & Cilgavimab)

54
Q

Bebtelovimab Dosing + adjustment

A

Slow IV push - once

No dose adjustment

55
Q

Evusheld Dosing + adjustment

A

Q6 months, IM

No dose adjustment

56
Q

Bebtelovimab DI + ADE

A

no many ADE

No DI

57
Q

Evusheld ADE + DI

A

Injection side reactions
Higher rate of Cardiac events
No DI

58
Q

(Val) Acyclovir prodrug of

A

Acyclovir

59
Q

Famciclovir is prodrug of

A

penciclovir

60
Q

(Val)Acyclovir MOA

A

** Requires Thymidine Kinase to activate drug **

Inhibits Viral DNA synthesis:

Inactivation of viral DNA polymerase -> competitive inhibitor of viral DNA polymerase -> incorporation not termination of Viral DNA

61
Q

Acyclovir Dosing adjustments

A

Renal dosed

62
Q

Acyclovir IV ADE

A

Phlebitis

Nephrotoxicty = slow infusion, hydrate to reduce

63
Q

Acyclovir-resistance

A
  1. Thymidine Kinase Alterations = Primary mechanism

2. DNA polymerase mutation = < 5% HSV resistance , uncommon

64
Q

Treatment for Acyclovir Resistant HSV

A
  1. HSV infection fails to respond after 4-5 days
  2. Switch to Foscarnet
  3. Foscarnet failure = switch to Cidofovir
  4. Therapy completed, rever to Acyclovir or valacyclovir PPX
65
Q

Cidofovir MOA

A

Nucleotide analogue of cytosine

Inhibits viral DNA synthesis:
Competitive inhibition of viral DNA polymerase -> incorporates into growing viral DNA chain, acts as chain terminator

66
Q

Cidofovir Active against….

A 
Resistant HSV
CMV
HHV6
BKV
Adenovirus
Ebola
Anthrax
Monekypox
67
Q

Cidofovir ADE

A

Nephrotoxicity = give with probenecid to decrease

Hematologic = Neutropenia ~ 20%

Cardiac arrest, Torsades de pointes, Vent tachycardia

68
Q

Cidofovir dose adjustment

A

100% renal elim, so req dose adjustment

69
Q

CMV is dependent on Viral kinase that include….

A

UL97
UL54
UL56

70
Q

(Val)Ganciclovir MOA

A

Nucleoside analogue of guanosine

Inhibits Viral DNA synthesis

Inactivation of viral DNA polymerase -> competitive inhibitor of viral DNA polymerase -> incorporation into and termination of viral DNA

** 10X more active against CMV than Acyclovir **

71
Q

Dosage forms of CMV treatments

A 
Ganciclovir = IV/PO
Valganciclovir = PO = prodrug = UL97 dependent
72
Q

Valganciclovir is dependent on….

A

UL97

73
Q

Valganciclovir dose adjustment

A

Renal clearance so have to dose adjust

74
Q

Valganciclovir activity

A

CMV

Acyclovir resistant HSV

75
Q

Ganciclovir ADE

A 
Neutropenia ~20%
Thrombocytopenia ~21%
Metabolic acidosis
N,V ~ 48%
rash
76
Q

Letermovir MOA

A

Inhibits CMV DNA terminase

Responsible for DNA cleavage

77
Q

Letermovir depends on…

A

UL56

78
Q

Letermovir limited to….

A

prophylaxis not treatment currently

CMV only also

79
Q

Letermovir CI

A

Not recommended in severe hepatic impairment

80
Q

Letermovir ADE

A

mostly GI

81
Q

Letermovir DI

A

Induces 2C9 = Warfarin + Phenytoin dec lvls

** dont use w/ Rifampin **

Inhibits 3A4, Amiodarone, Atorvastatin, Glyburide + rosiglitazone = inc lvls

82
Q

CMV Drug resistance

A

UL97 mutation

UL54 mutation

83
Q

UL97 mutations, which drugs can you use

A

Cidofovir
Foscarnet
Letermovir

84
Q

UL54 Mutation, which drugs can you use

A

Letermovir

Foscarnet maybe active

85
Q

Maribavir indication

A

used for refractory CMV

works at UL97

86
Q

Maribavir MOA

A

Multimodal inhibition of….

CMV DNA replication
Encapsidation
Nuclear egress of viral capsids

87
Q

Maribavir ADE

A

Mostly GI
some taste disorders**
some bone marrow toxicity

88
Q

Maribavir Dose adjustment

A

dont need for renal or hepatic impairment

89
Q

Maribavir DI

A

CYP3A4 inducers = dec serum conc of Maribavir

increase dose when suing w/ Carbamazepine, Phenobarbital, phenytoin primidone

Anti-Infectives Exam 3 (7 decks)

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