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pharmacology 4810 > Antiretroviral Agents MT2 > Flashcards

Antiretroviral Agents MT2 Flashcards

1
Q

this is a retrovirus of the lentivirus group; it uses host machinery to replicate, therefore it can’t survive outside the host cell for very long. Replication of this virus is constant in the host cell

A

human immunodeficiency virus (HIV)

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2
Q

is HIV a DNA or RNA virus

A

RNA

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3
Q

what cells do HIV target

A

CD4 lymphocytes

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4
Q

Abacavir, Emtricitabine, Lamivudine and Zidovudine all belong to this first-line class for HIV treatment

A

nucleoSIDE RT inhibitors (NRTI)

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5
Q

Tenofovir disoproxil fumarate and Tenofovir alafenamide belong to this first-line class for HIV treatment

A

nucleoTIDE RT inhibitors (NtRTI)

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6
Q

Doravirine, Efavirenz, Nevirapine, Etravirine and Rilpivirine all belong to this first-line class for HIV treatment

A

non-nucleoside RT inhibitors (nnRTI)

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7
Q

Bictegravir, Cabotegravir, Dolutegravir, Elvitegravir/cobi and Raltegravir all belong to this first-line class for HIV treatment

A

Integrase inhibitors (INSTI)

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8
Q

Atazanavir, Darunavir, Lopinavir/ritovanir and Ritovanir all belong to this first-line class for HIV treatment

A

Protease Inhibitors (PI)

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9
Q

Most PI’s and elvitegravir (INSTI) are used clinically in their “boosted” form; that is in combination with a CYP inhibitor (PK booster). this results in elevated drug concentrations of the PI or INSTI, which results in enhanced efficacy, reduced dosing frequency or both. which are the two PK boosters used?

A

Ritovanir and Cobistat (cobi)

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10
Q

does resistance occur within or between antiretroviral drug classes?

A

within not between

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11
Q

what are the two main drug interactions with antiretroviral agents

A
  • antacids, H2 receptor antagonists and PPIs can reduce acidic environment needs for absorption of some ARVs (e.g. rilprivirine - nnRTI and atazanavir - PI)
  • cytochrome P450 interactions are common, as well as interactions affecting other drug transport systems (e.g. P-glycoprotein, OAT and OCT systems)
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12
Q

true or false: ARVs may be inhibitors of CYP enzymes

A

false - may be substrates, inhibitors or inducers of CYP enzymes

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13
Q

Fostemasavir is in this second-line class for HIV treatment

A

attachments inhibitor (gp120 inhibitor)

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14
Q

Lenacapavir is in this second line class for HIV treatment

A

Capsid inhibitor

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15
Q

Maravrioc is in this second line class for HIV treatment

A

entry inhibitors (CCR5 co-receptor antagonist)

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16
Q

Enfuviritide is in this second line class for HIV treatment

A

Fusion inhibitors

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17
Q

what is the timeframe for the onset of CYP induction drug reactions?

A

enzymes are being produced thus days to weeks

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18
Q

what is the timeframe for the onset of CYP inhibition drug interactions

A

inactivating an enzyme that is already there thus a day or two

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19
Q

what is the mechanism of action of nucleoside/nucleotide RT inhibitors?

A

NRTI or NtRTI’s bind competitively to viral RT in place of natural nucleotide and act as chain terminators

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20
Q

NRTI or NtRTI?
these are synthetic nucleoside analogue prodrugs, therefore they must undergo triphosphorylation by intracellular enzymes to active form

A

NRTI

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21
Q

NRTI or NtRTI?
these are essentially a nucleotide monophosphate

A

NtRTI

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22
Q

Tenofovir disoproxil fumarate (TDF - old version) or Tenofovir alafenamide (TAF - new version)?
attachment of lipophilic groups allow passive drug diffusion across cell membranes - not stable in plasma and bloodstream, therefore most of TFV gets taken up into renal cells instead of CD4 target cells which can cause renal toxicity

A

TDF

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23
Q

Tenofovir disoproxil fumarate (TDF - old version) or Tenofovir alafenamide (TAF - new version)?
phosphonoamidate prodrug designed to be more stable in plasma vs other drug, therefore less plasma exposure to tenofovir, resulting in less uptake in renal tubular cells and less Renal and bone toxicity

A

TAF

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24
Q

these NRTI/NtRTI agents need dosing adjustment in renal impairment

A
  • emtricitabine
  • lamivudine
  • tenofovir
  • zidovudine
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25
Q

true or false: NRTI/NtRTI have no metabolism or effect on cytochrome P450 system

A

true

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26
Q

intracellular concentrations and half-life are of _________ (less/greater) clinical significance than plasma levels

A

greater

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27
Q

what is the route of administration for NRTIs (abacavir, emitricitabine, lamivudine) and NtRTI’s (TDF and TAF)?

A

PO/oral

28
Q

this NRTI requires HLA-B*5701 screening prior to treatment.

adverse effects of this medication include a hypersensitivity syndrome: presents as a flu-like illness (fever, rash, GI, fatigue, cough, respiratory symptoms) that occurs usually within first 6 weeks of tx -> MUST D/C DRUG AND NEVER RECHALLENGE - FATAL

may also be associated with increased risk of MI

A

abacavir

29
Q

what are the adverse effects of emtricitabine and lamivudine

A

headaches and nausea - but usually well tolerated

30
Q

adverse effects of this NtRTI include renal dysfunction, headaches, nausea, diarrhea, flatulence, increased risk of osteoporosis

A

TDF

31
Q

adverse effects of this NtRTI include increased cholesterol

A

TAF

32
Q

what is the mechanism of action of non-nucleoside RT inhibitors (e.g. doravirine, efavirenz and rilpivirine)

A

noncompetitive inhibitor of reverse transcriptase (RT) -> nnRTI’s bind to an inactive site on the RT to induce a conformational change in the 3D structure of there RT that greatly reduces its activity
active against HIV-1 strains only

33
Q

should efavirenz be taken with food or on an empty stomach in order to reduce intolerable side effects

A

fatty foods increases CNS penetration of efavirenz therefore should be taken on an empty stomach to reduce intolerable side effects

34
Q

what are some points to keep in mind for administration of oral rilpivarine regarding its absorption

A
  • should be taken with a high calorie meal (at least 550 kcal)
  • absorption is significantly reduced when co-administered with antacids. if H2RA is necessary, can administer rilpivarine 4 hours before or 12 hours after H2RA
35
Q

do nnRTIs have any effect on the cytochrome P450 system

A

yes - all are metabolized primarily by CYP 3A4 therefore nnRTI levels are reduced with coadministration of CYP 3A4 inducers and increased with CYP 3A4 inhibitors

efavirenz is an inducer of CYP 3A4
doravirine does not inhibit or induce CYP enzymes
rilpivarine is a moderate inducer of some CYP enzymes - it does not produce clinically sig. interactions at usual doses

36
Q

are nnRTIs administered PO or IV

A

doravirine and efavirenz are PO

rilpivirine is PO and IM

37
Q

this nnRTI is generally well tolerated. may cause nausea, drowsiness/dizziness, headache, insomnia/nightmares

A

doravirine

38
Q

this nnRTI may cause QT prolongation or depressed mood. chance of elevated cholesterol, hepatotoxicity and rash… if severe d/c

A

rilpivirine

39
Q

this nnRTI may cause CNS toxicity, dizziness, difficulty concentrating, insomnia. tolerance usually develops to all except abnormal dreams. may cause altered mood. chance of elevated cholesterol, hepatotoxitiy and rash… if severe d/c

A

efavirenz

40
Q

what is the mechanism of action of integrase inhibitors (bictegravir, cabotegravir, dolutegravir, elvitegravir/cobi)

A

inhibits the catalytic activity of HIV intergrase, preventing the integration of the HIV genome into the host genome in the early stages of HIV replication

41
Q

should integrase inhibitors be taken with or without food for optimal absorption

A

elvitegravir should be taken with food; the others may be taken with or without

42
Q

this integrase inhibitor is primarily metabolized by UGT1A1 with a minor UGT1A9 component

A

cabotegravir

43
Q

these integrase inhibitors are substrates of UGT 1A1 and CYP 3A4; not an inhibitor or inducer of CYP, UGT or any major transport systems

A

bictegravir and dolutegravir

44
Q

this integrase inhibitor is a substrate of both UGT 1A1 and CYP 3A4
- requires CYP inhibitor (cobistat) to permit once daily dosing
- may not be recommended in those with reduced renal fxn

A

elvitegravir

45
Q

what is the route of administration of integrase inhibitors

A

bictegravir, dolutegravir and elvitegravir are PO
cabotegravir can be PO or IM

46
Q

this integrase inhibitor must be taken with rilprivarine

A

cabotegravir

47
Q

what are some AE of integrase inhibitors

A

pretty well tolerated
- may get some nausea, diarrhea, headache

48
Q

what is the MOA of protease inhibitors

A

bind to HIV aspartyl protease to prevent proteolytic cleavage of HIV “gag” and “pol” poly proteins, which include essential structural and enzymatic components of the virus, thus producing immature, non-infectious virions

49
Q

should protease inhibitors be taken with food or on an empty stomach for optimal absorption

A

with food

50
Q

which protease inhibitors absorption is reduced if co-administered with antacids, H2RA’s, PPIs

A

atazanavir

51
Q

all protease inhibitors are metabolized by which enzyme

A

CYP 3A4

52
Q

all protease inhibitors are substrates of what type of transporters

A

p-glycoprotein drug transporters

53
Q

all protease inhibitors are inhibitors of what enzyme

A

CYP 3A4
* ritonavir is the most potent 3A4 inhibitor

54
Q

what is an important drug-drug interaction of protease inhibitors

A

ritovanir boosted PI’s and oral contraceptives -> alternative form of birth control should be used in this situation

55
Q

are protease inhibitors PO or IM

A

PO

56
Q

what are some AE for all protease inhibitors

A
  • GI (N/V/D)
  • increased cholesterol levels
  • metabolic side effects
57
Q

which protease inhibitor should caution be taken with regarding a sulfa allergy

A

darunavir (has sulfa moeity)

58
Q

this specific protease inhibitor has side effects such as: prolonged QT and renal impairment

A

atazanavir

59
Q

what is the MOA of fostemsavir, which is an attachment inhibitor (gp120 inhibitor)

A

fostemsavir is a prodrug of temsavir. temsavir bind to the viral envelope gp120 and interferes with viral attachment and entry of the virus

60
Q

is fostemsavir PO or IM

A

PO

61
Q

what is the MOA of lenacapvir which is a capsid inhibitor

A

directly binds to the interface between capsid protein subunits - multi-stage, selective inhibitor of HIV-1 capsid function therefore inhibits HIV-1 replication

62
Q

is lenacapavir PO or SC injection

A

SC injection following an oral lead in

63
Q

what is the MOA of maraviroc which is an entry inhibitor

A

binds to human chemokine receptor CCR5 in order to inhibit the interaction between the envelope glycoprotein (gp120) from CCR5-tropic HIV-1 strains

64
Q

is maraviroc PO or SC injection

A

PO

65
Q

what is the MOA of enfuvirtide which is a fusion inhibitor

A

binds to the gp41 glycoprotein to prevent conformation changes necessary for HIV to fuse to the CD4 cell membrane
* only active against HIV-1 strains

66
Q

is enfuviritide PO or SC injection

A

SC injection

pharmacology 4810 (12 decks)

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