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Flashcards in antiretrovirals Deck (110):
1

what are the five classes of antiretrovirals

1.) NRTIs. 2.) NNRTIs. 3.) protease inhibitors. 4.) entry inhibitors. 5.) integrase inhibitors

2

what is the mechanism of the NRTIs

they terminate viral DNA chain elongation. inhibition of the reverse transcriptase enzyme.

3

what kind of molecules are the NRTIs

they are nucleoside analogs.

4

what does zidovudine analog?

thymidine

5

what does stavudine analog

thymidine

6

what does didanosine analog

adensosine

7

what does tenofovir analog

adenosine

8

what does zalcitabine analog

cytosine

9

what does lamivudine analog

cytosine

10

what does emtricitabine analog

cytosine

11

what does abacavir analog

guanine

12

what is the SE of tenofovir

nephrotoxicity

13

what is the SE of abacavir

HSR

14

what are the SE for lamivudine/emtricitabine

few

15

what are the SE for zidovudine

anemia

16

what are the general class SE for NRTIs

lactic acidosis and Gi SE

17

How can the virus become resistant to the NRTIs

by mutation. if the virus mutates that base pair enough the drug becomes inactive.

18

what is the mechanism for NNRTis

binds directly to the reverse transcriptase enzyme and inhibits its action. right into the binding pocket.

19

what are the four common NNRTIs

1.) efavirenz, 2.) nevirapine, 3.) etravirine, 4.) rilpivirine

20

what are the SE for efavirenz

CNS symptoms such as vivid dreams, drowsiness. it is also teratogenic.

21

what are the SE for nevirapine

Rash, hepatitis and hepatitis necrosis.

22

what are the SE for etravirine

rash, increased LFTs.

23

what are the SE for rilpivirine

rash and QT prolongation.

24

what is the mechanism for protease inhibitors

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.