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Anti-Infectives Exam 3 > Lecture 3 - Antiviral Agent 2 > Flashcards

Lecture 3 - Antiviral Agent 2 Flashcards

1
Q

Hep A

A

RNA virus
Transmission: Fecal oral, sexual
Risks: Endemic travel, MSM, daycare

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2
Q

Hep B

A

DNA virus
transmission: Parenteral, sexual, vertical
Risks: MSMS, IV drug user, Liver transplant, HC worker,

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3
Q

Hep C

A

RNA virus, most problematic

Transmission: Parenteral, sexual vertical

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4
Q

Which Hep can cause liver damage?

A

Hep B and C

Hep A goes away

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5
Q

Hep A treatment

A

Self limiting, symptomatic treatment

Prevention = hepA vaccine

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6
Q

Hep B treatment

A

Can be chronic, use chronic antiviral

Prevention = HepB vaccine

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7
Q

Tenofovir & Entecavir have….

A

rapid activity, relatively safety, clinical experience

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8
Q

Lamivudine is…

A

relatively safe but more resistance

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9
Q

IFN-alfa isn’t really used due to….

A

unacceptable safety profile

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10
Q

Adefovir isn’t used much due to…

A

more resistance and nephrotoxicity

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11
Q

Drugs with low resistance barrier

A

Lamivudine, Emtricitabine

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12
Q

Drugs with low potency

A

Adefovir

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13
Q

Lamivudine (A.K.A 3TC) MOA

A

inhibits HBV DNA polymerase

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14
Q

Lamivudine DI

A

None clinically significant

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15
Q

Lamivudine Dose adjustment

A

renal dose/interval adjustment required

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16
Q

Lamivudine ADRs

A

Headache, fatigue, anemia, nausea

Mitochondrial toxicity**
Lactic acidosis**
Pancreatitis**

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17
Q

Adefovir MOA

A

inhibits HBV DNA polymerase

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18
Q

Adefovir ADRS

A

Nephrotoxicity

Decreased carotene lvls

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19
Q

Adefovir Dose adjustment

A

Renal dose/interval adjustment required

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20
Q

Adefovir DI

A

no sig interactions

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21
Q

Entecavir (MOA)

A

guanosine analog, inhibits HBV DNA polymerase

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22
Q

Entecavir ADRs

A

lactic aidosis
nausea
headache
dizziness

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23
Q

Entecavir DI

A

No sig interactions

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24
Q

Entecavir Dose adjustment

A

Renal dose/interval adjustment required

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25
Q

Emtricitabine FTC MOA

A

inhibits HBV DNA polymerase

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26
Q

Emtricitabine ADRs

A

hyperpigmentation of palms & soles**
lactic acidosis
headache
dizziness

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27
Q

Emtricitabine DI

A

no sig interactions

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28
Q

Emtricitabine Dosage adjustments

A

renal dose/interval adjustment req

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29
Q

tenofovir MOA

A

inhibit HBV DNA polymerase

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30
Q

Tenofovir ADRs

A

Osteoporosis
asthenia
renal toxicity

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31
Q

Tenofovir DI

A

PGP inhibitors / inducers

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32
Q

Tenofovir dosage adjustment

A

renal dose/interval adjustment required

more for TDF than TAF

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33
Q

TDF and TAF Tenofovir

A 
TDF = Viread = 300mg QD
TAF = Vemlidy = 25 mg QD
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34
Q

TAF doesn’t need dose adjustment when….

A

CrCl > 15 mL/min

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35
Q

Interferon Alfa 2a (Pegasus) MOA

A

Stimulates HLA Class I protein (immune enhancer)

longest 1/2 life

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36
Q

Interferon Alfa ADR

A 
flue like
lose hair
CNS = depression, confused, sucidial
Hematolgic
Endocrine
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37
Q

Interferon Alfa dose adjustment

A

No recommended Renal insufficiency CrCl < 50ml/min

38
Q

Interferon Alfa DI

A 
Theophylline = inc Theo conc
Zidovudine = inc myelosuppression
39
Q

Mutation that will knock out lamivudine is…

A

YMDD mutation single point

40
Q

What to do w/ LAM resistance?

A

Switch to TDF or TAF

41
Q

What to do w/ ETV resistance

A

Switch to TDF or TAF

42
Q

What to do w/ TDF+TAF resistance

A

Lam naive: Switch to ETV

LAM-R = Add ETV

43
Q

What to do if MDR HBV?

A

Switch to ETV + (TDF or TAF) combo

44
Q

Peginterferon alfa will work against which genotypes for HepC?

A

All of them

45
Q

Interferon alfa dose is adjusted based on…

A

Hemoglobin and hematocrit

also careful with depression

ESRD req adjustment

46
Q

Ribavirin MOA

A
  1. enhances immune clearance
  2. inhibition of IMPDH
  3. Inhibition of HCV RdRp
  4. RNA mutagenesis

used in combo

47
Q

Which genotypes can Ribavirin be used for?

A

all of them

48
Q

Ribavirin DI

A

azathioprine increases cytopenias

Abacavir, zidovudine = lactic acidosis

49
Q

Ribavirin dose adjustment

A

req renal adjustment

also adjust for cell count, if dec then dec dose

50
Q

Ribavirin ADR

A

Shit load of side effects

dont use men/women childbearing age

51
Q

Where do Protease inhibitors work?

A

NS3

52
Q

Protease inhibitors

A 
Grazoprevir = GZR
Voxilaprevir = VOX
Glecaprevir = GLE
53
Q

Where do Replication Complex inhibitors work

A

NS5A

54
Q

Replication Complex Inhibitors

A 
Elbasvir = EBR
Ledipasvir = LDV
Ombitasvir = OBV
Velpatasvir = VEL
Pibrentasvir = PIB
55
Q

Where do NUC inhibitors work?

A

NS5B (Polymerase)

56
Q

NUC inhibitors

A

Sofosbuvir = SOF

57
Q

Where do Non-NUC inhibitors work?

A

NS5B (Polymerase)

58
Q

Non-NUC inhibitors

A

Dasabuvir = DSV

59
Q

-evir Drug Dose adjustments?

A

No dose adjustment

60
Q

Elbasvir DI & Dose adjustment

A

No dose adjustment

DI = 3A4 Substrate

61
Q

Ledipasvir DI & Dose adjustment

A

Amiodarone***, Antacids, H2 blockers, PPI

Dont use for CrCl < 30

62
Q

Sofusbuvir DI & Dose adjustment

A

Use caution with CrCl < 30 ml/min*****

Avoid Amiodarone + strong PGP inducers

63
Q

Drugs active against all genotypes HepC

A

Sofosbuvir-Velpatasvir-Voxilaprevir (Vosevi)
Sofosbuvir-Velpatasvir (Epclusa)
Glecaprevir/Pibrentasvir (Mavyret)

64
Q

Recommended drugs to avoid for severe liver dysfunction

A

GZR/EBV

IFN

65
Q

-evir are substrates of….

A

3A4

Dependent on transport protein metabolism too

potential inhibit and interact with plenty of other drug classes

66
Q

-asvir interactions with….

A

3A4, transport proteins for metabolism too

Ledipasvir doesn’t req 3A4 adjustment but others do

67
Q

Drugs that you dont want to give with doses of > 20mg of PPI

A

LDV/SOF

Ledipasvir/Sofosbuvir

68
Q

Drugs that you dont want to give with PPI at all

A

SOF/VEL

Sofosbuvir/velpatasvir

69
Q

NRTIs MOA

A
  1. inhibit HIV RNA dependent DNA polymerase, inhibit viral replication
  2. Incorporate into growing viral DNA chain-chain terminator
70
Q

Shared NRTI’s side effects?

A

General: N,V,D

Mitochondiral toxicity

Hypersensitivity = abacavir**
Renal failure = tenofovir**
Hyperpigmentation = emtricitabine**
Anemia = Zidovudine***

71
Q

NRTI Mitochondrial toxicity MOA

A

inhibition of mitochondrial DNA polymerase, impaired synthesis of mitchondrial enzymes, impaired ATP production

~50% mortality in most severe cases

72
Q

Early signs for NRTI Mitochondrial toxicity

A

N, abdominal pain, weight loss/tachycardia, hyperventilation, weakness

73
Q

Highest risk groups for NRTI Mitochondrial Toxicity

A

Combo of….

DDI + D4T
DDI + hydroxyurea

Prolonged duration of therapy
Females
Obese
Pregnant patients

74
Q

NRTIs effect on Lipids…

A

increase in Cholesterol potentially

Older more effect than newer ones

75
Q

Facial and extremity wasting with or without central adiposity associated with….

A

Stavudine
Didanosine
Zidovudine

Also older age, higher TG at start of therapy, CD4 nadir < 200

76
Q

Changing d4T to TDF can cause….

A

reversal in lipids and limb fats

77
Q

Abacavir info

A

AKA ABC

Early, w/I 6wks (Hypersensitivity syndrome (5-8%), fever,rsh, N,V,D)

Late ( CVD)

78
Q

Before pts on Abacavir, do a test for….

A

HLA-B*5701, correlates with susceptibility to hypersensitivity

Dont give if positive
Do not rechallenge

79
Q

Advantages of ABC

A
  1. coformulated with INSTI in 1st line regimen = Triumeq
  2. Long hx of use
  3. Not really cleared
80
Q

Disadvantages of ABC

A
  1. Hypersensitivity

2. CVD

81
Q

TAF is….

A

Alafenamide

82
Q

TDF is….

A

Disoproxil Fumarate

83
Q

Tenofovir ADE

A

Nephrotoxicity-AKI and Fanconi Syndrome

Osteopenia

84
Q

Benefits of TAF > TDF

A
  1. less impact on BMD
  2. Less impact on markers of renal tubular dysfunction
  3. Low dose allows small tab coformulations
85
Q

Benefits of TDF > TAF

A
  1. used for longer
  2. multiple coformulations
  3. TAF has weight gain
  4. recommended in pregnancy
  5. available as generic with 3TC
86
Q

NRTI that are really eliminated and dosed except….

A

Abacavir

87
Q

NNRTI specific mutation

A

K103N

88
Q

NRTI specific mutations

A

M184V = most common, Lamivudine + Emtricitabine resistance, increased activity to Tenofovir and ZDV

K65R = resistance to most except ZDV

89
Q

Abacavir DI

A

excessive Alcohol

Methadone

90
Q

Didanosine DI

A

Allopurinol, consider reducing didanosine by 50%

Cidofovir

91
Q

Stavudine DI

A

Zidovudine = Dont co admin

92
Q

Tenofovir DI

A

Atazanavir = 300mg Atazanavir w/ 100mg ritonavir (booster) when used with tenofovir

Didanosine = reduce didanosine to 250mg QD

Anti-Infectives Exam 3 (7 decks)

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