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PHRM 840 > Antivirals > Flashcards

Antivirals Flashcards

1
Q

Viruses depend on what to live?

A

host cell machinery

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2
Q

Antiviral drugs are only active against what type viruses?

A

only replicating viruses, not latent viruses

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3
Q

What are 6 sites antiviral drugs work at?

A
  1. viral attachment and entry
  2. uncoating
  3. nucleic acid synthesis
  4. transcription/translation
  5. packaging/assembly
  6. release
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4
Q

What drugs block viral attachment and entry?

A

Enfuvirtide
Docosanol
Maraviroc
Palivizumab

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5
Q

What drugs block penetration?

A

interferon-alfa

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6
Q

What drugs block uncoating?

A

amantadine and rimantadine

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7
Q

What drugs block nucleic acid synthesis?

A

NRTIS, NNRTIs, nucleoside/nucleotide analogs

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8
Q

What drugs block integration/transcription?

A

INSTIs

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9
Q

What drug block viral protein synthesis?

A

PIs

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10
Q

What drugs block viral release from host cell?

A

neurominidase inhibitors

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11
Q

How is influenza classified?

A

antigenic differences

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12
Q

Antigenic variation in influenza occur as?

A

drift and shifts

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13
Q

Drifts are

A

epidemics, minor changes like point mutations

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14
Q

Shifts are

A

pandemics, major genetic changes resulting in alterations of antigen structure usually caused by reassortment

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15
Q

Anti-influenza drugs may work at sites of?

A

packaging/assembly and release

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16
Q

Neurominidase inhibitors are active against?

A

Both influenza A and B

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17
Q

What are 3 neurominidase inhibitors?

A

Oseltamivir
Zanamivir
Peramivir

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18
Q

Oseltamivir

A

Tamiflu

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19
Q

Zanamivir

A

Relenza Diskhaler

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20
Q

Peramivir

A

Rapivab

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21
Q

Oseltamivir formulation and half life

A

oral, 6-10 hrs

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22
Q

Oseltamivir excretion

A

kidney

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23
Q

Oseltamivir dose adjustment

A

renal dysfunction

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24
Q

Oseltamivir adverse effects

A

GI upset, headache

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25
Q

Zanamivir formulation

A

inhaler

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26
Q

Zanamivir adverse effects

A

potential bronchospasms so not recommended for pts with asthma/COPD

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27
Q

Peramivir formulation

A

single IV dose

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28
Q

Peramivir adverse effects

A

diarrhea, skin hypersensitivity

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29
Q

All neurominidase inhibitors all have the potential to cause?

A

neuropsychiatric events like confusion delirium, and hallucinations

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30
Q

What drug blocks influenza endonuclease and prevents cap snatching?

A

Baloxavir Marboxil

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31
Q

Baloxavir Marboxil

A

Xofluza

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32
Q

Baloxavir Marboxil approved when and formulation

A

2018, single oral dose

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33
Q

Baloxavir Marboxil metabolism

A

UGT1A3 (glucuronidation) and CYP3A4

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34
Q

Baloxavir Marboxil half life and excretion

A

79.1 hrs and primarily in feces

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35
Q

Baloxavir Marboxil adverse effects and counseling

A

2 degree bacterial infections and avoid taking with dairy products

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36
Q

Large, double stranded DNA genome, icosahedral capsid and envelope

A

Herpes viruses

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37
Q

HSV1 is typically associated with?

A

orolabial ulcers

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38
Q

HSV1 drug treatments

A

Docosanol OTC, Peniciclovir

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39
Q

Docosanol

A

Abreva

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40
Q

Docosanol (Abreva) moa

A

prevents viral entry

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41
Q

Penciclovir

A

Denavir

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42
Q

Penciclovir moa

A

triphosphate form competes with dGTP for viral polymerase, inhibits replication

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43
Q

HSV2 is associated with

A

anogenital ulcers

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44
Q

Commonly known as chickenpox, can later emerge as herpes zoster

A

Varicella zoster virus

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45
Q

Infects severely immunocompromised/HIV pts, infection often the result of viral reactivation

A

cytomegalovirus

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46
Q

Guanosine analog that is monophosphorylated by viral TK

A

acyclovir

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47
Q

Oral nucleoside analog for treatment of HSV2

A

acyclovir

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48
Q

Acyclovir moa

A

nucleoside analogs prevent viral replication

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49
Q

Acyclovir

A

Zovirax

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50
Q

Acyclovir formulation and absorption

A

topical and IV, poorly absorbed but small doses can improve absorption

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51
Q

Acyclovir half life and excretion

A

2.5 hrs, excreted in urine

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52
Q

Acyclovir SE and monitoring

A

GI upset, neurotoxicity, and renal impairment

monitor urinalysis, BUN, SCr, LFTs, CBC

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53
Q

Prodrug of acyclovir used for treatment of HSV2

A

valacyclovir

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54
Q

Valacyclovir

A

Valtrex

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55
Q

Valacyclovir metabolism and absorption

A

converted by 1st pass intestinal or hepatic metabolism and rapid GI absorptions

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56
Q

Valacyclovir formulation, half life and excetion

A

oral, 2.5 hr, and excreted in urine

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57
Q

Valacyclovir ADE and drug interactions

A

thrombotic thrombocytopenic purpura/hemolytic uremic syndrome and interacts with cimetidine or probenecid

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58
Q

Does acyclovir or valacyclovir achieve better oral absorption?

A

valacyclovir

59
Q

CMV treatments

A

Ganciclovir
Valganciclovir
Foscarnet
Cidofovir

60
Q

Ganciclovir formulation

A

IV, solution for injection or ophthalmic use

61
Q

For refractory cases of CMV

A

Foscarnet

Cidofovir

62
Q

CMV prophylaxis

A

Letermovir

63
Q

Foscarnet

64
Q

Letermovir

65
Q

Valganciclovir

66
Q

monophosphorylated by viral kinase (UL97 gene). Di- and tri- phosphorylated by host enzymes. Competes with dGTP for viral DNA polymerase incorporation into viral DNA

A

Ganciclovir

67
Q

Ganciclovir half live and excretion

A

4 h, excreted in urine

68
Q

Ganciclovir ADE

A

GI upset, myelosuppression, infection, fever, increased serum creatinine

69
Q

Ganciclovir boxed warnings

A

hematologic toxicity, impairment of fertility, feta toxicity, mutagenesis/carcinogenesis

70
Q

Ganciclovir monitoring

A

CBC with differential and platelet count, SCr, ophthalmic exams

71
Q

Valganciclovir formulation, elimination and counseling

A

once daily tab, renal elimination and take with food

72
Q

Noncompetitive inhibitor of viral DNA polymerase

73
Q

Foscarnet formulation, half life and excretion

A

IV and 3-7 hrs, can remain in bone for several months, renal excretion

74
Q

Foscarnet boxed warning

A

renal impairment, seizures

75
Q

Foscarnet ADE

A

HA, fever, GI upset, electrolyte imbalance, anemia, QTc prolongation

76
Q

Foscarnet monitoring

A

CrCl, ECG/EKG, electrolyes, CBC

77
Q

Selective inhibitor of viral DNA synthesis

78
Q

Cidofovir formulation, half life and excretion

A

IV, 2.6 hrs, renal excretion

79
Q

Cidofovir boxed warning

A

nephrotoxicity, neutropenia, carcinogenic/teratogenic

80
Q

Vaccine preventable liver infection found in the stool and blood of people who are infected and spread when someone unknowingly ingests the virus

A

Hepatitis A

81
Q

Serious liver infection that’s easily preventable by a vaccine and spread sexually or by contaminated needles/blood

A

Hepatitis B

82
Q

Infection that attacks the liver and leads to inflammation; virus is spread by contact with contaminated blood from sharing needles or from unsterile tattoo equipment

A

Hepatitis C

83
Q

Occurs in people who are also infected with the hepatitis B virus to supply envelope proteins (HBsAgs) for assembling a virion; “Delta hepatitis”

A

Hepatitis D

84
Q

Found in stood and spread when someone unknowingly ingests the virus; common is east and south Asia, vaccine licensed in China

A

Hepatitis E

85
Q

Can be calledGBV‐C‐ namedaftersurgeon,G.Barker,whofellillwithanon‐Anon‐Bhepatitis); single‐ strandedRNAvirusclassifiedintheFlaviviridaefamily.Noconclusiveevidencetoindicatecauseoffulminantorchronic liverdisease.Transmittedbybloodandsexualcontact.

A

Hepatitis G

86
Q

Both HBV and HDV utilize what for cell entry?

A

NTCP, sodium taurocholate cotransporting polypeptide

87
Q

Medication only available in EU

A

Bulevirtide

88
Q

Bulevirtide moa

A

entry inhibitor that binds to NTCP, blocking the ability of HDV to enter hepatocytes , so high barrier to resistance is anticipated

89
Q

Which infection is acute and self limiting

90
Q

Which infection is can be both acute and lead to a chronic infection, cirrhosis, liver cancer or death

A

HBV and HCV

91
Q

Non-enveloped, single stranded, positive sense RNA virus, acute, usually self-limiting, infection. Supportive care.

92
Q

Enveloped, partially double-stranded DNA (circular) virus, acute (supportive care) and chronic infection. Rates of chronic infections 2 to >10% of acute infections. Viral DNA can insert into human chromosome and later REACTIVATE (primary concern)!

93
Q

Enveloped, single stranded, positive sense HAV and HBV are RNA virus, chronic infection. Curable.

94
Q

Vaccine preventable infections

A

HAV and HBV

95
Q

Hepatitis A vaccine, doses and recommended in?

A

Vaqta, 2 doses, 1 yr or older

96
Q

Hepatitis B vaccine that is 3 doses for birth to adult

A

Recombivax and Engerix

97
Q

Hepatitis B vaccine that is 2 doses for >18yoa

98
Q

Hepatits B vaccine that is 3 doses for >18yoa

99
Q

Treatment goals of HAV infection

A

no specific treatment, self limiting, supportive care

100
Q

Treatment goals of chronic HBV infection (3)

A
  1. suppression of HBV DNA to undetectable levels
  2. seroconversion of HBeAg from positive to negative
  3. reduction in elevated serum aminotransferase levels
101
Q

Treatment goals of chronic HCV infection

A

viral eradication

102
Q

First line treatment for HBV

A

nucleoside reverse transcriptase inhibitors: TDF, TAF, and Entecavir

103
Q

Tenofovir disproxil fumarate

104
Q

Tenofovir alafenamide

105
Q

Entecavir

A

Baaraclude

106
Q

What are treatments used for HBV but use is limited because of resistance?

A

Adefovir and Lamivudine

107
Q

Adefovir

108
Q

Lamivudine

109
Q

Why should patients be tested for HIV prior to HBV therapy (2)

A
  1. HBV drugs have activity against HIV
  2. HBV can be treated with 1 drug bit it is not acceptable to treat HIV with 1 drug (partial drug exposure = increased potential for reisistance)
110
Q

TDF moa

A

AMP analog inhibits HBV polymerase and HBV replication

111
Q

TDF boxed warning

A

post-treatment acute exacerbation of HBV

112
Q

TDF ADE

A

GI upset, potential renal toxicity and bone loss

113
Q

TDF metabolism

A

intracellular hydrolysis to tenofovir then phosphoylated to active tenofovir diphosphate

114
Q

TDF half life and excretion

A

17 hrs and excreted in urine

115
Q

TAF moa

A

tenofovir prodrug, allows slow delivery into lymphoid cells and hepatocytes, reduced dosing and toxicity

116
Q

TAF DI

A

P-gp substrate, avoid use with phenytoin, rifampin and St. John’s wort

117
Q

Entecavir

118
Q

Entecavir moa

A

guanosine nucleoside analog that competitively inhibits all three functions of HBV DNA polymerase; 1. base priming 2. reverse transcription of negative strand and 3. synthesis of the positive strand of HBV DNA

119
Q

Entecavir boxed warning

A

severe, acute HBV exacerbations; HIV/HBV coinfection, lactic acidosis, and hepatomegaly

120
Q

Entecavir half life and counseling point

A

128-149 hrs and take with food

121
Q

Entecavir metabolism

A

minor hepatic glucuronide/sulfate conjugation

122
Q

Entecavir excretion

A

kidneys so needs to be renally adjusted

123
Q

Entecavir ADE

A

hepatic impairment, ALT elevation, peripheral edema, ascites, hematuria, nephrotoxicity, increased SCr

124
Q

Boxed warning of direct acting antivirals

A

Risk of HBV reactivation upon DAA cessation in co-infected pts so test for HBV before starting DAA for HCV

125
Q

DAA contraindications

A

CI with CYP3A5 inducers

126
Q

Mavyret

A

Glecaprevir/Pibrentasivir

127
Q

Mavyret moa

A

combination of NS3/4A PI and NS5A inhibitors

128
Q

Mavyret ADE

A

HA, fatigue, GI upset, hypoglycemia in diabetes pts

129
Q

Mavyret half life, excretion and counseling points

A

6 and 13 hrs, excreted in feces and should be taken with food

130
Q

Epclusa

A

Sofosbuvir/Velpatasvir

131
Q

Epclusa moa

A

combinationof NS5B and NS5A inhibitors

132
Q

Epclusa ADE

A

HA, fatigue, GI upset, hypoglycemia in diabetics

133
Q

Epclusa half life, excretion and counseling points

A

0.5 and 15 hrs, excreted in urine and feces and can be taken with or without food but do not take with PPIs

134
Q

Ribavirin

A

Ribatol, Ribashere

135
Q

Ribavirin moa

A

Guanosine analog, phosphorylated intracellularly by host enzymes; may interfere with the synthesis of GTP, inhibit capping of viral mRNA, and inhibit viral RNA–dependent polymerase

136
Q

Ribavirin boxed warning

A

Do not use alone for HCV, hemolytic anemia,

137
Q

Ribavirin ADE

A

CNS effects, GI upset, dermatologic effects, hematologic effects (neutropenia, anemia), muscle weakness, hepatic toxicity (can increase hepatotoxic effects of all NRTIs).

138
Q

Ribavirin half life and excretion

A

44-298 hrs and excreted in urine/feces

139
Q

Ribavirin bioavilability

A

increases with high-fat meals and decreased when co-administered with antacids

140
Q

Vosevi moa

A

Combination of protease inhibitor (Voxilaprevir) NS5A (Velpatasvir) and NS5B (Sofosbuvir) inhibitors

141
Q

Vosevi boxed warning

A

HepB reactivation

142
Q

Vosevi counseling point

A

take with food

143
Q

Vosevi ADE

A

fatigue, HA, nausea, diarrhea, insomnia

PHRM 840 (9 decks)

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