antiretrovirals Flashcards
1
Q
what are the five classes of antiretrovirals
A
1.) NRTIs. 2.) NNRTIs. 3.) protease inhibitors. 4.) entry inhibitors. 5.) integrase inhibitors
2
Q
what is the mechanism of the NRTIs
A
they terminate viral DNA chain elongation. inhibition of the reverse transcriptase enzyme.
3
Q
what kind of molecules are the NRTIs
A
they are nucleoside analogs.
4
Q
what does zidovudine analog?
A
thymidine
5
Q
what does stavudine analog
A
thymidine
6
Q
what does didanosine analog
A
adensosine
7
Q
what does tenofovir analog
A
adenosine
8
Q
what does zalcitabine analog
A
cytosine
9
Q
what does lamivudine analog
A
cytosine
10
Q
what does emtricitabine analog
A
cytosine
11
Q
what does abacavir analog
A
guanine
12
Q
what is the SE of tenofovir
A
nephrotoxicity
13
Q
what is the SE of abacavir
A
HSR
14
Q
what are the SE for lamivudine/emtricitabine
A
few
15
Q
what are the SE for zidovudine
A
anemia
16
Q
what are the general class SE for NRTIs
A
lactic acidosis and Gi SE
17
Q
How can the virus become resistant to the NRTIs
A
by mutation. if the virus mutates that base pair enough the drug becomes inactive.
18
Q
what is the mechanism for NNRTis
A
binds directly to the reverse transcriptase enzyme and inhibits its action. right into the binding pocket.
19
Q
what are the four common NNRTIs
A
1.) efavirenz, 2.) nevirapine, 3.) etravirine, 4.) rilpivirine
20
Q
what are the SE for efavirenz
A
CNS symptoms such as vivid dreams, drowsiness. it is also teratogenic.
21
Q
what are the SE for nevirapine
A
Rash, hepatitis and hepatitis necrosis.
22
Q
what are the SE for etravirine
A
rash, increased LFTs.
23
Q
what are the SE for rilpivirine
A
rash and QT prolongation.
24
Q
what is the mechanism for protease inhibitors
A
binds within the pocket of the protease inhibiting the binding of the virus. without the protease cleavage the virus cannot infect. the polyprotein needs processing
25
what positive effect does ritonavir have when given in combination with other PI? what is the mechanism?
it interacts and increases activity. it inhibits P4503A4 in the liver and gut and also inhibits P-glycoprotein transport.
26
what is the rationale behond giving ritonavir
reduce the frequency of dosing, improve pill burden, improved ability to suppress strains of resistant virus. improves regimen efficacy.
27
what are the PI class toxicities
GI intolerance -nausea, vomit, diarrhea. metabolic toxicities -dyslipidemia, hyperglycemia, lipodystrophy.
28
what is the mechanism of enfuvirtide
inhibits the entry of the virus. binds to GP41 and inhibits the formation of the entry pore, so the virus cannot enter the cell.
29
what are the SE of enfuvirtide
local injection site reaction (pain, erythema, nodules, cysts), increased rate of bacterial pneumonia, HSR (rare)
30
what is maraviroc?
CCR5 antagonist. chemokine receptor inhibitor. this is a coreceptor that is necessary for infection.
31
what are the SE maraviroc
hepatotoxicity rare. cough, fever, URI, rash, MSK, abdominal pain, dizziness.
32
what are the three integrase inhibitors
raltegravir, elvitegravir, dolutegravir
33
what are the adverse effects of the integrase inhibitors?
few. nausea, HA, diarrhea, pyrexia, myopathy or rhabdomyolysis.
34
what do the integrase inhibitors do?
they inhibit the integration of viral DNA into the host genome
35
what is the recommendation for antiretroviral treatment
recommended for all HIV infected patients to reduce the risk of progression. also based on the CD4 count.
36
what should patients starting ART be willing to do?
commit to long-term treatment
37
what is HAART
highly active antiretroviral therapy.
38
what are the basics of HAART
combination therapy of at least 3 active agents. utilization of multiple classes. there are typically three agents that represent 2 classes of agents. this is combination therapy or cocktail therapy.
39
what are common HAART regimens
PI (with ritonavir boost) + 2 NRTIs, NNRTI + 2 NRTIs, integrase inhibitors + 2 NRTIs
40
what is the recommended NNRTI based HAART
efavirenz + (lamivudine or emtricitabine) + tenofovir
41
what is the recommended PI-based HAART
atazanavir/ritonavir or darunavir/ritonavir + (lamivudine or emtricitabine) + tenofovir
42
what is the integrase-based recommended HAART
raltegravir/elvitegravir/dolutegravir + (lamivudine or emtricitabine) + tenofovir
43
what are the goals of HAART
suppression of viral load, restoration of immune function, quality of life, reduce morbidity mortality, minimize risk for resistance.
44
therapy goals for HAART
undetectable viral load <20 within the first 24-48 weeks of therapy. increased CD4 count (this trails the viral load).
45
what should be done if the patient does not reach the HAART goals
change treatment.
46
if resistance is acquired by the HIV is it permanent
yes.
47
can cross-resistance occur with antiretroviral treatment
yes.
48
what is resistance to HAART atrtributable to?
adherence and attainment of goals.
49
how do we monitor the success of HIV treatment
viral load, CD4 count, side effects
50
what is the family for HCV
flavivirdae.
51
what is the genome for HCV
ssRNA with 7 genotypes.
52
how is HCV transmitted>
percutaneous, permucosal route. IV drugs, medical supplies, tattoos.
53
is there an effective vaccine for HCV
no.
54
is HCV curable
yes, with effective treatment
55
what is the mechanism for interferon
induces genes that establish an antiviral state within the cell. usually pegylated
56
what are the concerns for interferon treatment
not viral specific. flu-like illness, cytopenias, depression, fatigue, difficult treatment course. there are many patietns with contraindications.
57
what are the contraindications for interferon
baseline cytopenia or psychiatric problems.
58
what is ribavirin
nucleoside analog
59
what are the major SE for ribavirin
hemolytic anemia and teratogen.
60
what are the new classes for treatment of HCV
nucleotide/side NS5B polymerase inhibitors, NS5A inhibitors, NS3/4A protease inhibitors.
61
what class is sofosbuvir
NS5B inhibitor -a nucleoside/tide polymerase inhibitor.
62
what is the class for ledipasvir?
NS5A inhibitor.
63
what is the class for simeprevir?
NS3/4A protease inhibitor.
64
what is the class for telapevir?
NS3/4A protease inhibitor.
65
what is the class for boceprevir
NS3/4A protease inhibitor.
66
what is the mechanism for sofosbuvir?
inhibits NS5B polymerase of HCV. this is an RNA-dependent RNA polymerase. it becomes phosphorylated and competes with viral uridine (natural) to cause chain termination. a
67
is sofosbuvir active across all HCV genotypes?
yes.
68
what are the toxicity for sofosbuvir
relatively safe. fatigue, HA, GI SE, anemia possible.
69
what is the mechanism for ledipasvir
inhibits viral NS5A a phophoprotein required for replication.
70
what are the toxicities for ledipasvir
relatively safe. fatigue, HA, GI SE possible.
71
what is the mechanism of action for simeprevir?
prevents viral maturation through inhibition of protein synthesis.
72
what is the mechanism for boceprevir
prevention of viral maturation through inhibition of protein synthesis.
73
what is the mechanism for telaprevir
prevention of viral maturation through inhibition of protein synthesis.
74
what is the class for the "previr"
these are the NS3/4A protease inhibitors.
75
what is the mechanism for all "previr"
prevention of viral maturation through inhibition of protein synthesis.
76
what are the SE for "previr"
anemia, rash, GI side effects, drug interactiond
77
what do we think when we hear protease inhibitors for viral therapy
drug interactions.
78
what is the approach to HCV therapy
combination is standard
79
what is the goal of HCV response
sustained virologic response or undetected RNA 12-24 weeks after therapy.
80
what is SVR synonymous with in HCV treatment?
cure.
81
do we use combination therapy for HCV and how many drugs is typical if yes?
yes. more than 2, with multiple mechanisms of action.
82
what is the mechanism of action for the guanosine nucleoside antivirals?
activated upon phosphorylation, which requires a cell infected with Herpesvirdae and is expressing thymidine kinase. inhibition of replication of the viral DNA.
83
what is the mechanism for acyclovir
phosphorylation by cellular enzymes and thus competes with DAN analogues to cause viral chain termination
84
what is acyclovir primarily active against
HSV and VZV
85
what is valacyclovir
prodrug of acyclovir that is converted upon oral administration.
86
what is penciclovir
structure and MOA similar to acyclovir. often topical.
87
what is famciclovir
prodrug of penciclovir given orally.
88
what are the toxicities for acyclovir
CNS -malaise, HA, confusion. nausea/vomit, diarrhea, renal dysfunction caused by high doses that crystalize in kidney'
89
what is ganciclovir used for
HSV, VZV, CMV.
90
is acyclovir used for CMV?
no. inactive against CMV
91
what are the adverse effects for ganciclovir
myelosuppression (neutropenia need to monitor), CNS (seizures, confusion, HA). hepatotoxic and some GI intolerance.
92
how can we increased the bioavailability of ganciclovir?
take with food increase 6-9%
93
foscarnet is active against which viruses
herpesvirdae and HIV.
94
what is the mechanism of action for foscarnet
direct inhibition of herpes DNA polymerase or HIV reverse transcriptase.
95
what are useful things to know about foscarnet
does not undergo significant cellular metabolism, and is active against acyclovir/penciclovir/ganciclovir resistant viruses.
96
what is an issue with foscarnet?
safety. nephrotoxicity. electrolyte/metabolic disorders (calcemia/phophatemia/hypomagnesemia/hypokalemia. CNS side effects (tremor, irritability, seizures, hallucinosis). myelosuppression.
97
what is the treatment of choice for herpes?
acyclovir
98
what is the treatment of choice for CMV
ganciclovir.
99
which antiviral is used for resistant viruses
foscarnet
100
what is the best treatment for influenza
vaccination
101
when do we use influenza treatment other than vaccinations
when caught early, if it moderately limits the length of illness, there is some benefit for critically ill patients.
102
what is the class for oseltamivir and zanamivir
neuraminidase inhibitors.
103
what is the mechanism for oseltamivir and zanamivir
inhibit neuraminidase and stops the penetration of the virus into the respiratory system.
104
what strain of flu are the neuraminidase inhibitors good for?
both A and B
105
what are the benefits of using the neuraminidase inhibitors
there is 30% more rapid resolution of symptoms. significantly reduces the rates of complication (bronchitis. pneumonia). generally well tolerated
106
when do we have to start neuraminidase inhibitors
the first 48 hours of symptoms and continue for 5 days.
107
what are the SE of the neuraminidase ihibitors
GI (nausea/vomiting/diarrhea), neuropsychiatric events (anxiety, agitation, altered mental status)
108
what are the unique SE of zanamavir
since it is inhaled there could be bronchospasms.
109
when do we use chemoprophylaxis for flu
througout flu season and post-exposure for a short periofd.
110
who gets chemoprophylaxis for flu
high risk and vaccinations were given post exposure, unvaccinated who provide care for high risk, immune deficiency and dont respond to vaccinations, influenza outbreak, any unvaccinated who wishes to avoid.
