Antivirals Flashcards
1
Q
Viruses depend on what to live?
A
host cell machinery
2
Q
Antiviral drugs are only active against what type viruses?
A
only replicating viruses, not latent viruses
3
Q
What are 6 sites antiviral drugs work at?
A
- viral attachment and entry
- uncoating
- nucleic acid synthesis
- transcription/translation
- packaging/assembly
- release
4
Q
What drugs block viral attachment and entry?
A
Enfuvirtide
Docosanol
Maraviroc
Palivizumab
5
Q
What drugs block penetration?
A
interferon-alfa
6
Q
What drugs block uncoating?
A
amantadine and rimantadine
7
Q
What drugs block nucleic acid synthesis?
A
NRTIS, NNRTIs, nucleoside/nucleotide analogs
8
Q
What drugs block integration/transcription?
A
INSTIs
9
Q
What drug block viral protein synthesis?
A
PIs
10
Q
What drugs block viral release from host cell?
A
neurominidase inhibitors
11
Q
How is influenza classified?
A
antigenic differences
12
Q
Antigenic variation in influenza occur as?
A
drift and shifts
13
Q
Drifts are
A
epidemics, minor changes like point mutations
14
Q
Shifts are
A
pandemics, major genetic changes resulting in alterations of antigen structure usually caused by reassortment
15
Q
Anti-influenza drugs may work at sites of?
A
packaging/assembly and release
16
Q
Neurominidase inhibitors are active against?
A
Both influenza A and B
17
Q
What are 3 neurominidase inhibitors?
A
Oseltamivir
Zanamivir
Peramivir
18
Q
Oseltamivir
A
Tamiflu
19
Q
Zanamivir
A
Relenza Diskhaler
20
Q
Peramivir
A
Rapivab
21
Q
Oseltamivir formulation and half life
A
oral, 6-10 hrs
22
Q
Oseltamivir excretion
A
kidney
23
Q
Oseltamivir dose adjustment
A
renal dysfunction
24
Q
Oseltamivir adverse effects
A
GI upset, headache
25
Zanamivir formulation
inhaler
26
Zanamivir adverse effects
potential bronchospasms so not recommended for pts with asthma/COPD
27
Peramivir formulation
single IV dose
28
Peramivir adverse effects
diarrhea, skin hypersensitivity
29
All neurominidase inhibitors all have the potential to cause?
neuropsychiatric events like confusion delirium, and hallucinations
30
What drug blocks influenza endonuclease and prevents cap snatching?
Baloxavir Marboxil
31
Baloxavir Marboxil
Xofluza
32
Baloxavir Marboxil approved when and formulation
2018, single oral dose
33
Baloxavir Marboxil metabolism
UGT1A3 (glucuronidation) and CYP3A4
34
Baloxavir Marboxil half life and excretion
79.1 hrs and primarily in feces
35
Baloxavir Marboxil adverse effects and counseling
2 degree bacterial infections and avoid taking with dairy products
36
Large, double stranded DNA genome, icosahedral capsid and envelope
Herpes viruses
37
HSV1 is typically associated with?
orolabial ulcers
38
HSV1 drug treatments
Docosanol OTC, Peniciclovir
39
Docosanol
Abreva
40
Docosanol (Abreva) moa
prevents viral entry
41
Penciclovir
Denavir
42
Penciclovir moa
triphosphate form competes with dGTP for viral polymerase, inhibits replication
43
HSV2 is associated with
anogenital ulcers
44
Commonly known as chickenpox, can later emerge as herpes zoster
Varicella zoster virus
45
Infects severely immunocompromised/HIV pts, infection often the result of viral reactivation
cytomegalovirus
46
Guanosine analog that is monophosphorylated by viral TK
acyclovir
47
Oral nucleoside analog for treatment of HSV2
acyclovir
48
Acyclovir moa
nucleoside analogs prevent viral replication
49
Acyclovir
Zovirax
50
Acyclovir formulation and absorption
topical and IV, poorly absorbed but small doses can improve absorption
51
Acyclovir half life and excretion
2.5 hrs, excreted in urine
52
Acyclovir SE and monitoring
GI upset, neurotoxicity, and renal impairment
| monitor urinalysis, BUN, SCr, LFTs, CBC
53
Prodrug of acyclovir used for treatment of HSV2
valacyclovir
54
Valacyclovir
Valtrex
55
Valacyclovir metabolism and absorption
converted by 1st pass intestinal or hepatic metabolism and rapid GI absorptions
56
Valacyclovir formulation, half life and excetion
oral, 2.5 hr, and excreted in urine
57
Valacyclovir ADE and drug interactions
thrombotic thrombocytopenic purpura/hemolytic uremic syndrome and interacts with cimetidine or probenecid
58
Does acyclovir or valacyclovir achieve better oral absorption?
valacyclovir
59
CMV treatments
Ganciclovir
Valganciclovir
Foscarnet
Cidofovir
60
Ganciclovir formulation
IV, solution for injection or ophthalmic use
61
For refractory cases of CMV
Foscarnet
| Cidofovir
62
CMV prophylaxis
Letermovir
63
Foscarnet
Foscavir
64
Letermovir
Prevymis
65
Valganciclovir
Valcyte
66
monophosphorylated by viral kinase (UL97 gene). Di- and tri- phosphorylated by host enzymes. Competes with dGTP for viral DNA polymerase incorporation into viral DNA
Ganciclovir
67
Ganciclovir half live and excretion
4 h, excreted in urine
68
Ganciclovir ADE
GI upset, myelosuppression, infection, fever, increased serum creatinine
69
Ganciclovir boxed warnings
hematologic toxicity, impairment of fertility, feta toxicity, mutagenesis/carcinogenesis
70
Ganciclovir monitoring
CBC with differential and platelet count, SCr, ophthalmic exams
71
Valganciclovir formulation, elimination and counseling
once daily tab, renal elimination and take with food
72
Noncompetitive inhibitor of viral DNA polymerase
Foscarnet
73
Foscarnet formulation, half life and excretion
IV and 3-7 hrs, can remain in bone for several months, renal excretion
74
Foscarnet boxed warning
renal impairment, seizures
75
Foscarnet ADE
HA, fever, GI upset, electrolyte imbalance, anemia, QTc prolongation
76
Foscarnet monitoring
CrCl, ECG/EKG, electrolyes, CBC
77
Selective inhibitor of viral DNA synthesis
Cidofovir
78
Cidofovir formulation, half life and excretion
IV, 2.6 hrs, renal excretion
79
Cidofovir boxed warning
nephrotoxicity, neutropenia, carcinogenic/teratogenic
80
Vaccine preventable liver infection found in the stool and blood of people who are infected and spread when someone unknowingly ingests the virus
Hepatitis A
81
Serious liver infection that's easily preventable by a vaccine and spread sexually or by contaminated needles/blood
Hepatitis B
82
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
Hepatitis C
83
Occurs in people who are also infected with the hepatitis B virus to supply envelope proteins (HBsAgs) for assembling a virion; "Delta hepatitis"
Hepatitis D
84
Found in stood and spread when someone unknowingly ingests the virus; common is east and south Asia, vaccine licensed in China
Hepatitis E
85
Can be called GBV‐C‐ named after surgeon, G. Barker, who fell ill with a non‐A non‐B hepatitis); single‐ stranded RNA virus classified in the Flaviviridae family. No conclusive evidence to indicate cause of fulminant or chronic liver disease. Transmitted by blood and sexual contact.
Hepatitis G
86
Both HBV and HDV utilize what for cell entry?
NTCP, sodium taurocholate cotransporting polypeptide
87
Medication only available in EU
Bulevirtide
88
Bulevirtide moa
entry inhibitor that binds to NTCP, blocking the ability of HDV to enter hepatocytes , so high barrier to resistance is anticipated
89
Which infection is acute and self limiting
HAV
90
Which infection is can be both acute and lead to a chronic infection, cirrhosis, liver cancer or death
HBV and HCV
91
Non-enveloped, single stranded, positive sense RNA virus, acute, usually self-limiting, infection. Supportive care.
HAV
92
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)!
HBV
93
Enveloped, single stranded, positive sense HAV and HBV are RNA virus, chronic infection. Curable.
HCV
94
Vaccine preventable infections
HAV and HBV
95
Hepatitis A vaccine, doses and recommended in?
Vaqta, 2 doses, 1 yr or older
96
Hepatitis B vaccine that is 3 doses for birth to adult
Recombivax and Engerix
97
Hepatitis B vaccine that is 2 doses for >18yoa
Heplisav
98
Hepatits B vaccine that is 3 doses for >18yoa
TwinRix
99
Treatment goals of HAV infection
no specific treatment, self limiting, supportive care
100
Treatment goals of chronic HBV infection (3)
1. suppression of HBV DNA to undetectable levels
2. seroconversion of HBeAg from positive to negative
3. reduction in elevated serum aminotransferase levels
101
Treatment goals of chronic HCV infection
viral eradication
102
First line treatment for HBV
nucleoside reverse transcriptase inhibitors: TDF, TAF, and Entecavir
103
Tenofovir disproxil fumarate
Viread
104
Tenofovir alafenamide
Vemlidy
105
Entecavir
Baaraclude
106
What are treatments used for HBV but use is limited because of resistance?
Adefovir and Lamivudine
107
Adefovir
Hepsera
108
Lamivudine
Epivir
109
Why should patients be tested for HIV prior to HBV therapy (2)
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
TDF moa
AMP analog inhibits HBV polymerase and HBV replication
111
TDF boxed warning
post-treatment acute exacerbation of HBV
112
TDF ADE
GI upset, potential renal toxicity and bone loss
113
TDF metabolism
intracellular hydrolysis to tenofovir then phosphoylated to active tenofovir diphosphate
114
TDF half life and excretion
17 hrs and excreted in urine
115
TAF moa
tenofovir prodrug, allows slow delivery into lymphoid cells and hepatocytes, reduced dosing and toxicity
116
TAF DI
P-gp substrate, avoid use with phenytoin, rifampin and St. John's wort
117
Entecavir
Baraclude
118
Entecavir moa
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
Entecavir boxed warning
severe, acute HBV exacerbations; HIV/HBV coinfection, lactic acidosis, and hepatomegaly
120
Entecavir half life and counseling point
128-149 hrs and take with food
121
Entecavir metabolism
minor hepatic glucuronide/sulfate conjugation
122
Entecavir excretion
kidneys so needs to be renally adjusted
123
Entecavir ADE
hepatic impairment, ALT elevation, peripheral edema, ascites, hematuria, nephrotoxicity, increased SCr
124
Boxed warning of direct acting antivirals
Risk of HBV reactivation upon DAA cessation in co-infected pts so test for HBV before starting DAA for HCV
125
DAA contraindications
CI with CYP3A5 inducers
126
Mavyret
Glecaprevir/Pibrentasivir
127
Mavyret moa
combination of NS3/4A PI and NS5A inhibitors
128
Mavyret ADE
HA, fatigue, GI upset, hypoglycemia in diabetes pts
129
Mavyret half life, excretion and counseling points
6 and 13 hrs, excreted in feces and should be taken with food
130
Epclusa
Sofosbuvir/Velpatasvir
131
Epclusa moa
combinationof NS5B and NS5A inhibitors
132
Epclusa ADE
HA, fatigue, GI upset, hypoglycemia in diabetics
133
Epclusa half life, excretion and counseling points
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
Ribavirin
Ribatol, Ribashere
135
Ribavirin moa
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
Ribavirin boxed warning
Do not use alone for HCV, hemolytic anemia,
137
Ribavirin ADE
CNS effects, GI upset, dermatologic effects, hematologic effects (neutropenia, anemia), muscle weakness, hepatic toxicity (can increase hepatotoxic effects of all NRTIs).
138
Ribavirin half life and excretion
44-298 hrs and excreted in urine/feces
139
Ribavirin bioavilability
increases with high-fat meals and decreased when co-administered with antacids
140
Vosevi moa
Combination of protease inhibitor (Voxilaprevir) NS5A (Velpatasvir) and NS5B (Sofosbuvir) inhibitors
141
Vosevi boxed warning
HepB reactivation
142
Vosevi counseling point
take with food
143
Vosevi ADE
fatigue, HA, nausea, diarrhea, insomnia
