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Anti-Infectives Exam 3 > Lecture 4 - Antiviral Agent 3 > Flashcards

Lecture 4 - Antiviral Agent 3 Flashcards

1
Q

Nevirapine ADE

A

Rash = dose titration
Most severe form - Erythema Multiforme

Hepatitis = AVOID in women with higher CD4 counts

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2
Q

Efavirenz ADE

A

CV - Dyslipidemia
Rash
CNS

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3
Q

Etravirine ADE

A

Rash
CNS, less than efavirenz
CV - Dyslipidemia

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4
Q

Rilpivirine ADE

A

Rash
CNS
CV - Dyslipidemia

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5
Q

Doravirine ADE

A

Rash
CNS = much less than Efavirenz, 8.8% vs 37% dizziness, 12.1 vs 25.5% abnormal dreams
** Positive effects on lipids **

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6
Q

NNRTI drugs are strong inducers so they will….

A

reduce lvls of substrate drug

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7
Q

Antidepressants that are less effected by NNRTI

A

Fluoxetine
Fluvoxamine
Paroxetine

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8
Q

Enzyme inducers reduce lvls of NNRTIs are….

A 
Rifampin
Rifabutin
Phenytoin
Phenobarbital
Carbamazepine
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9
Q

Enzyme inhibitors that increase lvls of NNRTIs

A 
Itraconazole
Voriconazole
Fluconazole
Posaconazole
Isavuconazonium
Clarithromycin
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10
Q

Most common NNRTI Resistance Mutations

A

K103N = wipe out 1st gen NNRTI

Y181C

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11
Q

Importnat points about NNRTI resistance

A

Extensive cross-resistance between 1st gen, excludes….
Doravirine
Etravirine
Rilpivirine

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12
Q

Protease inhibitor MOA

A

interfere with viral replication by blocking the protease enzyme involved in the production of structural proteins-results in imperfect non-infectious virus

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13
Q

Protease inhibitors will do what to lvls of substrate drug?

A

increase

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14
Q

Ribavirin should be avoided with

A

didaosine
stavudine
zidovudine

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15
Q

Sofosbuvir should be avoided with

A

tipranavir

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16
Q

Ledipasvir/Sofosbuvir can be used with….

A

Most ARVs

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17
Q

Glecaprevir/Pibrentasvir should not be used with

A

atazanavir
ritonavir-containing regimens
efavirenz
etravirine

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18
Q

Elbasvir/Grazoprevir should not be used with…

A 
Cobicistat
efavirenz
etravirine
nevirapine
or HIV protease inhibitors
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19
Q

Giving Azole with Protease inhib?

A

increased QT prolongation

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20
Q

Giving Protease inhib with anti-psychotics

A

increase side effects

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21
Q

Giving protease inhib with PDE5?

A

decrease dose for ED, dont use in PAH

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22
Q

Protease inhib effect on methadone?

A

lvl decreased**

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23
Q

Protease inhib with OC?

A

decrease in Hormone lvls

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24
Q

Protease inhib with Warfarin?

A

play with doses

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25
Q

Protease inhib with Steroids?

A

use beclomethasone as alternative inhalation steroid

use less potent steroids

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26
Q

pH altering with Protease inhibitors

A 
Atazanavir = greatst risk for dec solubility an absorption
Ritonavir = next
Lopinavir = less risk for solubility changes
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27
Q

Unique SE Atazanavir

A

Asymptomatic jaundice

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28
Q

Unique SE Indinavir

A

Kidney Stones

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29
Q

Unique SE Fosamprenavir

A

Severe skin rash

30
Q

Unique SE Tipranavir

A

Intracranial hemorrhage

31
Q

Unique SE Saquinavir

A

QT prolongation

32
Q

Lipodystrophy with Protease Inhibitors

A

up to 50-80% of pts after 12-18 months

Risk factors: > 65yrs old
low BW before therapy
using boosted PI combo
Prolonged used

33
Q

Impact of PIs to Diabetes

A

Longer PI use associated with increased onset of diabetes

TGs also associated with diabetes

34
Q

Special SE Indinavir

A

Lots of Kidney Stones, stay hydrated

35
Q

SE Lopinavir/Ritonavir

A

Long PR interval

36
Q

Atazanavir SE

A

Increased bilirubinemia = jaundice

37
Q

Fosamprenavir SE

A

Hypersensitivity, sulfonamide allergy

38
Q

Darunavir SE

A

Hepatitis

Caution w/ severe sulfa allergy

39
Q

Tipranavir SE

A

Severe Hepatitis

Intracranial hemorrhage

40
Q

Darunavir will…

A

maintain more activity through mutations compared to other drugs

41
Q

Mariviroc (entry Inhibitor) MOA

A

CCR5 Antagonist

Binds to CCR5 co-receptor site on the host cell and prevents penetration of HIV

42
Q

Mariviroc can only be used for….

A

R5 not X4

Prior to initiation, requires tropism test to evaluate the predominant virus

If virus is mixed x4/r5 or x4 virus, Mariviroc will fail

43
Q

ADE Mariviroc

A

Hepatotoxicity

44
Q

Mariviroc DI

A

Azole, PI

strong inhibition = increase in Mariviroc
Strong inducers = dec in Mariviroc so need to inc dose

45
Q

How to avoid Mariviroc toxicity w/ enzyme inhibitor?

A

Decrease mariviroc dose to 150 BID

46
Q

Enfuvirtide (T-20) MOA

A

Fusion inhibitor

Binds to viral gp41 and prevents a conformational change required for fusion of the virus to the CD4 cell

47
Q

Enfuvirtide ADE

A

Injection site reactions
Hypersensitivity
Elevated CK

48
Q

Enfuviritide clearance?

A

no renal or hepatic, no dose adjustments

49
Q

Gas powered injection system?

A

Helps to to disperse drug so it doesn’t sit in one spot under the skin

leads to less injection site reactions

50
Q

Enfuvirtide Mutations & Resistance?

A

Gp41 (binding site) amino acid substitutions

51
Q

INSTI MOA

A

Prevents HIV integrase enzyme from inserting HIV genetic material into cellular DNA

52
Q

Which INSTI has lower bioavailability?

A

Elvitegravir

53
Q

INSTI SE profile?

A

***Weight gain
CNS
Rash
CK elevation

54
Q

Highest CNS SE of INSTI?

A

Efavirenz

Raltegravir also has decent amount

55
Q

ADE Elvitegravir

A
  1. need to use with Cobicistat, acts as booster

2. Cobicistat associated with more GI adverse effects

56
Q

Dolutegravir ADE?

A

Marked by CNS side effects**weird dreams

Hypersensitivity
Increase in LFTs in pts co-infected with HBC or HCV

57
Q

Which INSTIs avoided with Rifampin

A

EVG
BTG
CAB

58
Q

DHHS guidelines for HIV?

A

DTG for persons of child bearing age

59
Q

BIC only affected by…..

A

IRON

60
Q

Dofetilide should be avoided with….

A

INSTI

61
Q

When using Metformin with INSTI…..

A

dose has to be less than 1000mg daily

less so problem with BIC and CAB

62
Q

PPI not significant interaction wit INSTI when….

A

using a boosted combo

63
Q

INSTI resistance number

A

148Q

Mostly EV and RAL, less so BIC and DTG

64
Q

How to get passed Q148 mutation?

A

using higher dose of DTG

65
Q

BIC has most activity against….

A

wild type and G140S+Q140H mutation

66
Q

Ibalizumab

A

Used for extremely drug resistant HIV

Q2weeks

ADE: infusion related
DI: none
Cl: no adjustments

67
Q

Ibalizumab MOA

A

blocks postattachment HIV entry into CD4+ T-cells without altering normal cell function

68
Q

Fostemsavir

A

Attachment inhibitor, prodrug

used as a salvage. so add on with others

no renal or hepatic dose adjustment

69
Q

Fostemsavir ADE

A

QT prolonged

Hepatic dysfunction

70
Q

Avoid Fostemsavir with….

A

Efavirenz
Etravirine
Rifampin
Carbamazepine + Phenytoin

will dc lvl

71
Q

Fostemsavir effects on OATP1B1

A

inhibits it

need to dose adjust

Estrogen, Statins, Grazoprevir, Voxilaprevir

will inc lvl od drug elim

Anti-Infectives Exam 3 (7 decks)

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