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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
Remdesivir ADE
Rash Nephrotoxicity hepatic toxicity
26
Remdesivir DI
Hepatic enzyme + P-GP inducers not recommended due to potential decrease in remdesivir drug conc ie. Rifamycins, Carbamazepine, Phenobarbital, Efavirenz, Nevirapine, Rilpivirine
27
Dexamethasone MOA
Binding to Pro/3CLpro (viral protease), inhibition of neutrophil apoptosis/demargination, promotion of anti-inflammatory genes (IL-10)
28
Dexamethasone dose adjustment
Nah
29
Dexamethasone CI
Current MTB, HSV
30
Dexamethasone DI
moderate CYP450, 3A4 inducer
31
Dexamethasone ADE
Reactivation of HBV, HSV, TB, dysglycemias, CNS changes
32
Tocilizumab MOA
Monoclonal antibody to IL-6 receptor, treats cytokine release syndrome
33
Tocilizumab Dosing adjustments
None IV only, given once
34
Tocilizumab CI & DI
Dont give in ppl with low BC Dont give with immunosuppressants
35
Tocilizumab ADE
``` HSV/VZV reactivation Opportunistic infections** TB Thrombosis** GI perforation Hypersensitivity ```
36
Baracitinib MOA
inhibit clatkhrin-mediated endocytosis and thereby inhibit viral entry, modulates hematopoiesis and immune cell function JAK1 inhib
37
Baracitinib Dose adjustments + clearance
50% w/ renal dysfunction = 2mg 75% renal clearance
38
Baracitinib DI
Probenecid dec clearance | Azathiorine and cyclosporine inc cytopenias
39
Baracitinib ADE
``` Cytopenias** Opportunistic infections** Thrombosis** Hepatotoxicity Dyslipidemia Malignancy HSV,VSV reactivation ```
40
Nirmatrelvir w/ ritonavir (Paxlovid)
Protease inhibitor w/ booster Nirmatrelvir: 3CLpro or nsp5 protease inhibitor Ritonavir: CYP450 enzyme inhibitor (acts as booster)
41
Paxlovid renal dose adjustment
50% with renal dysfunction
42
Paxlovid CI
Severe renal dysfunction
43
Paxlovid DI
Potent CYP3A4 inhib
44
Paxlovid ADE
Mostly GI Dysguesia = impaired taste Rebound phenomena
45
Enzyme inducers that reduce lvls of Paxlovid
``` Rifampin Rifabutin Phenytoin Phenobarbital Carbamazepine ```
46
Enzyme inhibitors that increase lvls of Paxlovid
``` Itraconazole Voriconazole Fluconazole Posaconazole Isavuconazonium Clarithromycin ```
47
Molnupiravir MOA
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
Molnupiravir Dose adjustments
none
49
Molnupiravir DI
none significant
50
Molnupirvir CI
Pregnancy | Child bearing age not on barrier contraception
51
Molnupirvir ADE
Teratogenicity Cartilage + bone growth abnormalities < 18yrs old D + N
52
Drugs of choice for mild-moderate ovid
Remdesivir Paxlovid Bebtelovimab
53
Drug used for PrEP?
Evusheld (Tixagevimab & Cilgavimab)
54
Bebtelovimab Dosing + adjustment
Slow IV push - once | No dose adjustment
55
Evusheld Dosing + adjustment
Q6 months, IM | No dose adjustment
56
Bebtelovimab DI + ADE
no many ADE | No DI
57
Evusheld ADE + DI
Injection side reactions Higher rate of Cardiac events No DI
58
(Val) Acyclovir prodrug of
Acyclovir
59
Famciclovir is prodrug of
penciclovir
60
(Val)Acyclovir MOA
** 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
Acyclovir Dosing adjustments
Renal dosed
62
Acyclovir IV ADE
Phlebitis Nephrotoxicty = slow infusion, hydrate to reduce
63
Acyclovir-resistance
1. Thymidine Kinase Alterations = Primary mechanism | 2. DNA polymerase mutation = < 5% HSV resistance , uncommon
64
Treatment for Acyclovir Resistant HSV
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
Cidofovir MOA
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
Cidofovir Active against....
``` Resistant HSV CMV HHV6 BKV Adenovirus Ebola Anthrax Monekypox ```
67
Cidofovir ADE
Nephrotoxicity = give with probenecid to decrease Hematologic = Neutropenia ~ 20% Cardiac arrest, Torsades de pointes, Vent tachycardia
68
Cidofovir dose adjustment
100% renal elim, so req dose adjustment
69
CMV is dependent on Viral kinase that include....
UL97 UL54 UL56
70
(Val)Ganciclovir MOA
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
Dosage forms of CMV treatments
``` Ganciclovir = IV/PO Valganciclovir = PO = prodrug = UL97 dependent ```
72
Valganciclovir is dependent on....
UL97
73
Valganciclovir dose adjustment
Renal clearance so have to dose adjust
74
Valganciclovir activity
CMV | Acyclovir resistant HSV
75
Ganciclovir ADE
``` Neutropenia ~20% Thrombocytopenia ~21% Metabolic acidosis N,V ~ 48% rash ```
76
Letermovir MOA
Inhibits CMV DNA terminase Responsible for DNA cleavage
77
Letermovir depends on...
UL56
78
Letermovir limited to....
prophylaxis not treatment currently CMV only also
79
Letermovir CI
Not recommended in severe hepatic impairment
80
Letermovir ADE
mostly GI
81
Letermovir DI
Induces 2C9 = Warfarin + Phenytoin dec lvls ** dont use w/ Rifampin ** Inhibits 3A4, Amiodarone, Atorvastatin, Glyburide + rosiglitazone = inc lvls
82
CMV Drug resistance
UL97 mutation | UL54 mutation
83
UL97 mutations, which drugs can you use
Cidofovir Foscarnet Letermovir
84
UL54 Mutation, which drugs can you use
Letermovir Foscarnet maybe active
85
Maribavir indication
used for refractory CMV works at UL97
86
Maribavir MOA
Multimodal inhibition of.... CMV DNA replication Encapsidation Nuclear egress of viral capsids
87
Maribavir ADE
Mostly GI some taste disorders** some bone marrow toxicity
88
Maribavir Dose adjustment
dont need for renal or hepatic impairment
89
Maribavir DI
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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