Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHRM 865 > Exam 4 - Antivirals (Medchem-Stahelin) > Flashcards

Exam 4 - Antivirals (Medchem-Stahelin) Flashcards

1
Q

There are ___#___ classes of viruses

A

6

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

what are the 6 different classes of viruses?

A 
double stranded DNA
single stranded DNA
single stranded RNA -- negative sense
single stranded RNA -- positive sense
retroviruses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Viruses Facts:

Obligate _________

A

intracellular parasites

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

Viruses Facts:

small or large genomes

A

small

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

Viruses Facts:

Must use ________ to replicate

A

host cell machinery

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

Viruses Facts:
Inhibit cellular pathways to promote replication —
what are 3 common pathways that are inhibited??

A 
cell death (apoptosis)
interferon
tumor suppression (p53)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Some viruses are surrounded by lipids?
If covered by lipids they are called _____
if no lipid layer they are called _____

A

enveloped

non enveloped….

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

what are some examples of enveloped viruses

A

HIV
influenza
herpes

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

what are some examples of non-enveloped viruses

A

picornavirus

adenovirus

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

General Virus Life cycle steps?

steps 1 - 8

A
  1. viral attachment/entry
  2. penetration
  3. uncoating
  4. nucleic acid synthesis
  5. integration / transcription
  6. viral protein synthesis
  7. packaging/assembly
  8. viral release
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what drug class will block viral release from the cell?

A

neuraminidase

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

HIV Fusion/Entry:

HIV _______ binds to _____ on target cell

A

gp120 (on HIV cell) binds to CD4 (on target cell)

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

HIV Fusion/Entry:
A conformational change will occur where a region of GP120 is exposed… the exposed region binds to the __________ receptor

A

cytokine

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

HIV Fusion/Entry:

The exposed region binds to a cytokine receptor will be ______ or ____ depending on the strain of HIV

A

CCR5 or CXCR4

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

_________ and ________ are HIV entry and fusion inhibitors

A

Enfuviritide

Maraviroc

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

Enfuviritide MOA?

A

binds to GP41 ON HIV and blocks the GP41 conformation

HIV fusion/entry inhibitor

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

Maraviroc MOA

A

binds to HUMAN CCR5 and blocks GP120 binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Enfuviritide binds to ________ cells

Maraviroc binds to ________ cells

A

Enfuv: binds to HIV cells
Mara: binds to human cells

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

Maraviroc:

can only be used in patients with HIV strains that _______

A

utilize CCR5

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

Enfuvirtide is only active against HIV ______

A

1

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

what are the 3 jobs of Reverse Transcriptase (RT)?

A

RNA dependent DNA Pol
Ribonuclease H
DNA-Dependent DNA Pol

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

Reverse transcriptase copies the ______ strand of RNA to make the _____ strand of DNA

A

plus strand RNA to minus strand DNA

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

NRTIs interfere with ____________ synthesis

A

1st and 2nd strand DNA synthesis

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

NRTIs MOA

A

they are nucloeside analogs that lack the 3’ OH =

  • competitive inhibitor of reverse transcriptase
  • DNA chain terminator (inhibits elongation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

T or F:

All NRTIs need to be activated/they are prodrugs

A

TRUE!

need to be activated by kinases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What activation step do NRTIs need?

A

need activated by kinases / need to get to a triphosphate (PO4- need to be added)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what NRTI has the longest half life

A

Tenofovir DISOPROXIL FUMURATE aka a prodrug…

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

problems with tenofovir disoproxil fumarate (TDF)?

A

TFV is eliminated by the kidney = if kidney issues, acute renal failure is more likely

and overall there is a larger reduction in bone mineral density compared to other NRTIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what is a different prodrug option for TFV?

A

TAF
(tenofovir alafenamide)
activated by a diff pathways/ fewer side effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what enzyme is used to activate TAF

A

CatA (cathepsin A)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

T or F:

The same kinase is used to add the 3 phosphates

A

FALSE! different kinases for each addition!1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

activated NRTIs compete with what 4 things to be incorporated into the growing DNA chain made by RT

A

4 things: dATP, dCTP, dGTP, and dTTP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

NRTIs have a higher affinity for______ than __________

A

higher affinity for HIV RT than cellular DNA pol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Tenofovir requires __#___ phosphorylation steps

A

2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Resistance to HIV Drugs:

why do mutations happen so quickly?

A

HIV pol is error prone
RT inhibitors are unable to suppress viral replication
Large amount of viruses are present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Resistance to HIV Drugs:

Rate at which mutations appear is _______ related to the serum ______

A

inversely related

serum drug concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

If there a drug has a ______ genetic barrier it is easy for a virus to become resistant

A

low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

if there a drug has a ____ genetic barrier it is hard for a virus to become resistant

A

high

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

what are the 2 kinds of resistance to NRTIs

A

Discriminatory mutations
or
Excision mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Explain discriminatory mutations towards NRTIs

A

helps the RT distinguish between normal dNTPs and NRTIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Explain excision mutations against NRTIs

A

promote removal of NRTIs after thye have been incorporated into the growing chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Single NRTI therapy has a ______ genetic barrier

A

low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

ADEs of NRTIs?

A

Mitochondrial toxicity
Lipoatrophy
Abacavir Hypersensitivity (black box)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Why does mitochondrial toxicity happen with NRTIs

A

NRTIs are selective for HIV RT over DNA pol alpha and beta but NOT gamma
(aka some NRTIs will inhibit DNA pol-gamma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

what effects are seen with mitochondrial toxicity

A 
!![anemia
granulocytopenia
myopathy
peripheral neuropathy
pancreatitis]!!
lactic acidosis
hepatic steatosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

what is lipoatrophy

A

loss of body fat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

what does Abacavir hypersensitivity look like?

A

Malaise
dizziness
headache
GI disturbances — STOP IMMEDIATELY if any of these

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

what allele should be tested for with Abacavir use

A

HLA-B 5701

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What are two of the recommended combo NRTI therapies

A

Tenofovir/Emtracitabine
or
Abacavir/Lamivudine
(emtracitabine and lamivudine are interchangable)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

what NRTI therapies are not recommended

A

monotherapy
dual NRTI therapy (if no other antivirals)
3 NRTI (because too much toxicity)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

MOA of NNRTIs
bind to what?
block what?

A

bind directly to the site of RT

block polymerization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

NRTIs or NNRTIs compete with nucleotides for binding (aka noncompetitive inhibitors)

A

NRTIs do compete

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

T or F:

NNRTIs need to be phosphorylated

A

false!!
NNRTIs do NOT need to be phosphorylated
(NRTIs doooo)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

2nd Gen NNRTIs

are designed to be inherently ________ which allows them to ________

A

inherently FLEXIBLE

allows them to bind in multiple orientations(can bind to mutants)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

ADEs of NNRTIs

A

rash
drug drug interactions
Nevirapine – hepatotoxicity (SJS rash)
Efavirenz – neuropsychiatric, teratogenic in primates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Specific ADEs of Nevirapine

A

it is a NNRTI

and it causes hepatotoxicity and SJS rash

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Specific ADE of Efavirenz

A

it is a NNRTI
neuropsychiatric
teratogenic in primates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Metabolism of NNRTIs

All metabolized by ________

A

CYP3A4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

NNRTI Facts:

They do or do not require activation

A

do not

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

NNRTI Facts:

Do or not compete with dNTPs

A

do not

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

NNRTI Facts:

Do or do not get incorporated into DNA

A

do not

62
Q

NNRTI Facts:

Do or do not bind to cellular DNA pol

A

do not

63
Q

NNRTI Facts:

A NNRTI mutation does or does not cause NRTI resistance

A

does not

64
Q

Integrase Enzyme works to do what?

A

insert HIV DNA into host cell DNA

65
Q

Integrase inserts HIV DNA into host cell DNA in what 2 steps?

A

3’ processing

Strand Transfer

66
Q

MOA of Integrase Inhibitors:
works by blocking what?

binds to what?

A

blocks the strand transfer step

binds to/chelates to metal ions and stabilizes enzyme-DNA complex

67
Q

Integrase uses ______ to catalyze insertion

A

divalent metal ions

68
Q

which INI has the highest genetic barrier (compared to other INIs)

A

Dolutegravir

69
Q

what drug is used with Elvitegravir to boost its concentrations

A

Cobicistat

70
Q

why is cobicistat given with Elvitegravir?

A

Cobi inhibits CYP3A4 = inhibits metabolism of Elvitegravir = higher elvitegravir levels

71
Q

Does dolutegravir have higher or lower barrier of resistance

A

higher barrier

72
Q

HIV Protease is an ______ protease

aka has a _____ in the active site

A

aspartic protease

has aspartic acid in active site

73
Q

HIV protease inhibitors are _______mimetics

and can of what 2 types?

A

transition state mimetics

could be peptidomimetic or nonpeptide compounds

74
Q

HIV Proteases job is what?

A
  • cut itself free and the cuts 4 other enzymes free from the long precursor
  • peptide bond cleavage via hydrolysis reaction reaction
75
Q

how do Protease inhibitors work?

A
  • they have a replaced amide bond with a non cleavable linkage
  • causes a conformation change/closes it
76
Q

All protease inhibitors except for _____ are consider peptidomimetics

A

tipranavir

77
Q

Metabolism of Protease Inhibitors:

Are they affected by CYP?

A

yes!

all are substrates and some are inhibitors

78
Q

what protease inhibitor is the most potent inhibitor of CYP enzymes

A

Ritonavir

79
Q

_______ is a protease inhibitor if given at low doses is used to increase serum concentrations of other antivirals

A

Ritonavir

80
Q

What are the two unique features of darunavir?

A

makes extensive hydrogen bonds with protease backbone

inhibits HIV protease dimerization

81
Q

Protease inhibitors:

have the lowest or highest genetic barrier compared to other antivirals

A

highest

82
Q

ADEs of Protease inhibitors?

A 
Hyperlipidemia
Insulin resistance/diabetes
lipodystrophy(changes in body fat)
Elevated liver function tests
possible increase bleeding risk in hemophiliacs
drug-drug interactions
83
Q

Herpes Virus:
(small or large)
(single or double) stranded
(RNA or DNA) virus

A

LARGE
DOUBLE
DNA

84
Q

Herpes Virus infections can be in what 2 forms of infection?

A

lytic (producing new virions)

latent (dormant)

85
Q

HSV-1 or HSV-2:

which one normally causes oral herpes

A

1

86
Q

HSV-1 or HSV-2:

which one normally causes genital herpes

A

2

87
Q

CMV (cytomegalovirus) usually not a problem unless what….

A

unless infection happens during fetal development
or
if immunocompromised pt

88
Q

what are some anti-herpesvirus agents

A 
acyclovir
valacyclovir
cidofovir
foscarnet
penciclvir
ganciclovir
valganciclovir...
89
Q

Acyclovir MOA?
competitive inhibitor of _______
competes with ____
is an (reversible or irreversible) inhibitor

A

competitive inhibitor of viral DNA pol (lower concentration needed for VIRAL DNA pol than host DNA pol)
competes with dGTP
is an irreversible inhibitor

90
Q

Acyclovir:

requires phosphorylation?

A

yes!! 3 phosphorylation events

91
Q

Acyclovir:

is incorporated into _______ and is a _____ terminator

A

DNA;

chain

92
Q

two main resistance mechanisms to acyclovir?

A

mutations in viral thymidine kinase
or
mutations viral DNA pol

93
Q

relation of valacyclovir to acyclovir?

A

valacyclovir is L-valyl ester of acycylovir…

converted to acyclovir by esterases in the intestines/liver

94
Q

Famciclovir and Penciclovir relation?

A

famciclovir is a prodrug of penciclovir

activated by 1st pass metab of intestine and liver

95
Q

MOA of famiciclovir/penciclovir (how is it different than acyclovir)

A

Fam and pen are competitive inhibitors of viral DNA pol BUT they do NOT cause immediate chain termination (they allow for short chain elongation)

96
Q

Penciclovir or Acyclovir:

which one has higher affinity for HSV TK (thymydine kinase)

A

penciclovir

97
Q

Penciclovir or Acyclovir:

which has higher affinity for HSV DNA pol

A

acycolovir

98
Q

Penciclovir or Acyclovir:

which one is more stable in HSV infected cells

A

penciclovir

99
Q

T or F: Topical penciclovir and famciclovir are great for topical herpes infections

A

FALSE: pencic is good but famcic needs 1st pass metab – aka famcic not used topically)

100
Q

Ganciclovir is structurally similar and same MOA as ________

but Ganciclovir is a better substrate for ______ than others

A

same MOA as penciclovir

better substrate for cytomegalovirus kinase

101
Q

Is toxicity in ganciclovir or acyclovir worse?

A

ganciclovir toxicity is worse

102
Q

Ganciclovir or Valganciclovir:
which one has good bioavailability?
which one has bad bioavailability?

A

Gancic: BAD bioavail
Valgan: GOOD bioavail

103
Q

Foscarnet Facts:

Needs or does not need phosphorylation for activity

A

does NOT need

104
Q

Foscarnet Facts:

what kind of compound is it

A

inorganic pyrophosphate compound

105
Q

MOA of Foscarnet:
It blocks ________ binding site of the viral ______
and inhibits cleavage of ________ from _______

A

blocks pyrophosphate binding site
of viral DNA pol;

cleavage of pyrophosphate from dNTPs

106
Q

Foscarnet Facts:

What is it used for?

A

CMV (like ganciclovir)

107
Q

Foscarnet Toxicities?

A 
renal insufficiency (RENAL ADJUST)
phosphate levels (hypo or hyper)
calcium levels (hypo or hyper)
headaches
108
Q

Foscarnet MOA:

inhibits what enzymes?

A

viral DNA pol
RNA pol
HIV RT

109
Q

Cidofovir:

acyclic nucleoside phosphonate analog of ______

A

cytosine

110
Q

MOA of Letermovir mechanism

A

inhibits terminase complex
(normally herpes virus DNA replicates through rolling circle mechanism and individual genomes need to be cut out by the terminase complex)

111
Q

influenza virus

(positive or negative) strand (DNA or RNA) virus

A

negative RNA virus

112
Q

3 types of influenza virus?

A

A,B,C

113
Q

Influenza Viruses: A, B or C

___ will infect humans and many different animals

A

A

114
Q

Influenza Viruses: A, B or C

___ widely circulates in ONLY humans

A

B

115
Q

Influenza Viruses: A, B or C

___ causes a very mild disease

A

C

116
Q

Influenza Viruses: A, B or C

____ and ____ cause epidemics nearly every winter

A

A and B

117
Q

Influenza A Subtypes are divided into two gene types: what are the two gene types?

A

H and N
H - hemagglutinin
N - Neuraminidase

118
Q

what are the two ways influenza viruses change?

A

Antigenic drift
or
Antigenic shift

119
Q

Antigenic Drift or Shift:

small changes to the virus

A

drift

120
Q

Antigenic Drift or Shift:

major abrupt change to the virus

A

shift

121
Q

Amantadine and Rimantandine:

inhibits __________ by targeting the ___ protein of influenza ____

A

inhibits penetration into host cells

by targeting M2 protein of influenza A

122
Q

ADEs of Amantadine?

A

GI intolerance
CNS effects
(worse in older people – over 60 years of age)

123
Q

influenza virus neuraminidase:
essential for virus _______
is located in the virus _______

A

replication

membrane

124
Q

influenza virus neuraminidase:

works to cleave the glycolytic bonds b/w terminal _____ and adjacent sugars

A

sialic acids

125
Q

influenza virus neuraminidase:
facilitates virus ________
______ binds to terminal sialic acid residues and _____ releases the virus

A

dissemination
HA (hemaglutinin)
NA (neuraminadase)

126
Q

what drugs are neuraminidase inhibitors

A

zanamavir

oseltamivir

127
Q

Oseltamivir:

Needs activated by liver – yes or no?

A

yes – it is a prodrug

128
Q

Oseltamivir:

it is an effective inhibitor of _____

A

NA (neuraminidase)

129
Q

Oseltamivir:

Effect depends on how soon therapy is started – need to initiate within _____ of first symptoms

A

48 hours

130
Q

Dosage form for Oseltamivir and Zanamivir?

A

Oseltam: oral
Zanamivir: oral inhaler…

131
Q

what is the newest neuraminidase inhibitor?
how is it administered?
it is a transition state analog of _____

A

Peramivir;
IV
sialic acid

132
Q

HCV stands for?

A

Hepatic C Virus

133
Q

Hepatic C Virus:
transmission via __________
Can cause what 3 things?

A

transmission via contaminated blood

can cause chronic hepatitis; liver cirrhosis, hepatocellular carcinoma

134
Q

what does SVR stand for and what is its definition?

A

sustained virological response

HCV RNA is undetectable for 6 months after treatment

135
Q

what is a common/nonspecific defense against viral infections

A

interferon

136
Q

what are the HCV NS3 protease inhibitors

A 
Telaprevir
Boceprevir
Paritaprevir
Simeprevir
Grazoprevir
Voxilaprevir
Glecaprevir
137
Q

HCV Protease Inhibitors:

target the HCV protease _____

A

NS3

138
Q

HCV Protease Inhibitors:

block the cleavage of the _____

A

HCV polyprotein

139
Q

HCV Protease Inhibitors:

what drugs are the 2nd gen/P1-P3 substrate analogs

A

Simeprevir

Paritaprevir

140
Q

HCV Protease Inhibitors:

what drugs are the 2nd gen/P2-P4 substrate analogs

A

Voxilaprevir
Glecaprevir
Grazoprevir

141
Q

HCV RNA Polymerase inhibitors:

_____ is known as the HCV RNA pol

A

NS5B

142
Q

what drug is a HCV RNA Polymerase inhibitor?

A

Sofosbuvir

143
Q

Sofosbuvir:

does it need phosphorylated?

A

yes

144
Q

Sofosbuvir Mechanism:

gets incorporate into _______ and causes ______

A

viral RNA chain (makes sense bc it is a RNA pol inhibitor..)

causes chain termination

145
Q

what drugs are HCV NS5A inhibitors

A 
Ombitasvir
Ledipasvir
Daclatasvir
Velpatasvir (2nd gen)
Pibrentasvir (2nd gen)
(-ASVIR)
146
Q

MOA of HCV NS5A inhibitors:

Inhibits both _______ and _______

A

viral RNA replication
and
assembly of release of infectious viral particles

147
Q

what drugs are HCV NS5B inhibitors?

A

Sofosbuvir
Dasabuvir
(-BUVIR)

148
Q

Blackbox warning for HCV direct acting antivirals (DAA)?

A

cases of fulminant hepatitis, hepatic failure, and death because of HBV (hepatic B virus) reactivation!!

149
Q

The blackbox warning for HCV agents happens when the DAAs are _______

A

alone/NOT used with an interferon

150
Q

Ways to decrease the HBV reactivation with HCV DAAs?

A

screen ALL pts for current or prior HBV infection
Monitor for HBV reactivation
talk to Drs who specialize in Hep B infections

– counsel patients to report side effects

151
Q

What are signs of serious liver injury?

A 
Yellow eyes or skin
light colored stools
fatigue/weakness
loss of appetite
N/V

PHRM 865 (59 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions