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🄼💊Chemotherapy/AntiViral/Botanicals > HIV Rx > Flashcards

HIV Rx Flashcards

1
Q

Which conditions cause Pancytopenia in HIV? (6)

A

Many HIV Pts Lose Cells Broadly

  1. •MAC
  2. •Histoplasmosis (Disseminated Fungal)
  3. •Parvovirus B19
  4. •CMV
  5. •Lymphoma
  6. •Medications [BAD PG] (Bactrim / AZT / Dapsone / Pyrimethamine / Ganciclovir)
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2
Q

What’s the normal CD4 count

A

800-1500

(ART should INC CD4 by 50-150 / year)

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3
Q

Virologic Suppression (Undetectable) is defined as what lab value?

A

Less than 50 HIV RNA copies

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4
Q

Describe the main differences between HIV2 and HIV1 (3)

A

HIV2 is…

  1. Endemic to West Africa
  2. Has longer Asx stage with lower viral loads and mortality
  3. May present as negative serology/viral load but with DEC CD4 suggestive of HIV
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5
Q

List the [Nucleoside/tide Reverse Transcriptase Inhibitors (NRTI)] (7)

A

ADELS TmZ

  1. Abavavir (ABC)
  2. Didanosine (ddl)
  3. Emtricitabine
  4. Lamivudine
  5. Stavudine
  6. Tenofovir
  7. Zidovudine (formely AZT)
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6
Q

NRTI MOA

A

Nucleoside/tide analogs lacking [3 OH group] that enter cell–>are phosphorylated–>form synthetic substrates that compete with native nucleotides–> terminate proviral DNA

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7
Q

NRTI Metabolism and half life

A

Renal Excretion with [half life=1-10 hours]

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8
Q

Explain how NRTI are able to be taken QD vs. BID

A

Intracell reservoirs of active anabolite DEC dosing frequency

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9
Q

NRTI SE (5)

A

Didanosine > Stavudine > Zidovudine

LHAMP

[Lactic Acidosis Hepatic Steatosis Syndrome]

Anemia

Myopathy

Pancreatitis

[HepB flare when discontinued]

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10
Q

Explain which drugs cause [Lactic Acidosis Hepatic Steatosis Syndrome] and why. (4)

A

NRTIs: Didanosine > Stavudine > Zidovudine > Tenofovir

… inhibit [DNA polymerase gamma] –> blocks mitochondria DNA synthesis –> [inhibits oxydative phosphorylation complex] activity–> INC cytosolic lactate –> [Lactic Acidosis Hepatic Steatosis Syndrome]

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11
Q

Which NRTIs cause [HepB Flare] when discontinued (3)

A

U LET these NRTIs go…there will be Hep problems!

Lamivudine (also–>Emtricitabine resistance)

Emtricitabine (also–>Lamivudine resistance)

Tenofovir

These NRTIs have Anti-HepB Activity so D/C –> HepB Flare

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12
Q

Abacavir Indication

A

Combo therapy for experienced HIV1

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13
Q

Abacavir SE

A

Hypersensitivity in [HLA-B 5701 + pts]. This is a Contraindication!!

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14
Q

Zidovudine Indication

A

Px Combo therapy for Both HIV in children/adult/prego

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15
Q

Zidovudine SE (2)

A

Anemia

[Granulocytopenia: Neutropenia]

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16
Q

Name the drugs contraindicated with Zidovudine (4)

A

Doves Really Creates Stinky Goop

Stavudine

Cotrimoxazole

Ganciclovir (BM tox)

Ribavirin (blocker)

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17
Q

Didanosine SE (3)

A

[Lactic Acidosis Hepatic Steatosis Syndrome]

Pancreatitis

Peripheral Neuropathy

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18
Q

Which NRTIs does Didanosine have drug-drug interactions with (3)

A

Stavudine - Cx

Zalcitabine - Cx

Tenofovir (INC serum Didanosine)

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19
Q

Which NRTIs are preferred for naive pts (2)

A

ET was a very naive alien

Emtricitabine

Tenofovir

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20
Q

Which NRTIs has DDI (drug-drug interaction) with Zalcitabine? (2)

A

Lem & Dal didn’t like Zal

Lamivudine

[Didanosine - Cx]

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21
Q

Tenofovir SE (3)

A

Hep B Flare

Nephrotoxic

[Lactic Acidosis Hepatic Steatosis Syndrome]

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22
Q

Describe the DDI between Tenofovir and Atazanavir

A

Tenofovir [DEC serum Atazanavir]

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23
Q

Name the [NonNucleotide Reverse Transcriptase inhibitors (NNRTIs)] (5)

A

NO DEENR!

Delavirdine

EfaVirenz

Etravirine

Nevirapine

Rilpivirine

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24
Q

NNRTIs MOA

A

Noncompetitve inhibitors that allosterically bind to RT and induce conformational change

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25
Q

NNRTIs metabolism and half life

A

NNRTI: [Rapidly absorbed and Liver metabolized]

Half life = (Delavirdine 2-11) to (EfaVirenz 40-55)

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26
Q

NNRTI Indication

A

HIV1

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27
Q

Can NNRTI be used as monotherapy? Why or why not?

A

NO! Rapid resistance development

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28
Q

What are the advantages and disadvantages (2) of NNRTI?

A

Advantage: Using NNRTI saves [Protease Inhibitors] for later

Disadvantage: Resistance and [Heavy influence on CYP450]

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29
Q

General NNRTI SE

A

Common DDI (heavy influence on CYP450)

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30
Q

EfaVirenz Indication

A

Initial HIV1 tx

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31
Q

EfaVirenz Contraindication

A

[1st Trimester preggo] or [Women planning to conceive]

EfaVirenz causes Birth and Transient CNS Defects

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32
Q

EfaVirenz DDI (2)

A

CYP3A4 inducer

  1. DEC serum Methadone
  2. DEC exposure to [Protease Inhibitors]
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33
Q

Nevirapine Indication

A

Combination HIV1; alternative to EfaVirenz in

[Naive women with pretx CD4<250]

and

[Men<400]

34
Q

Nevirapine Contraindication (2). What happens as a result?

A
  1. [Women with pretx Greater than 250 CD4]

or

  1. [Men Greater than 400 CD4]

These pts given Nevirapine –> Severe Hepatotoxicitiy

35
Q

Which DDI does Nevirapine have (2)

A

CYP3A4 inducer –>

DEC serum methadone

DEC exposure to Protease Inhibitors

36
Q

Name the [Protease Inhibitors] (8)

A

INDRAFTS

  1. Indinavir
  2. NeLFinavir
  3. Darunavir
  4. Ritonavir
  5. Atazanavir
  6. Fosamprenavir
  7. Tipranavir
  8. Saquinavir
37
Q

[Protease Inhibitors] MOA

A

INDRAFTS inhibit [HIV aspartyl protease] –> Blocks Proteolytic processing necessary for packaging & assembly –> Blocks maturation

38
Q

[Protease Inhibitor] General Characteristics (4)

A

PPPProtease Inhibitors!

  • [Poor PO bioavailability sometimes enhanced with fatty meals]
  • hePatic CYP metabolism
  • P-glycoprotein substrates
  • Plasma protein bound
39
Q

Describe the effectiveness of [Protease Inhibitors] to DEC Viral load

A

HIGHLY Effective when used as combo therapy

40
Q

[Protease Inhibitors (PTI)] SE (6)

A

Many PTIs Don’t NNeglect Lipids

  1. Metabolic Syndrome
  2. NVD and [Nephrolithiasis w/Indinavir]
  3. Paresthesia
  4. [Lipodystrophy-Chronic use]
  5. [DDIs-(Q W SPERMS)]
41
Q

Name the DDIs [Protease Inhibitors] have and why there is an interaction (7)

A

[Protease Inhibitors] Qlash’s With SPERMS!

Quinidine - CYP3A4 substrate

Warfarin - CYP3A4 substrate

St.John Wart - strong inducer of CYP3A4

Phenobarbital-strong inducer of CYP3A4

Ergotamine - CYP3A4 substrate

Rifampin - strong inducer of CYP3A4 **

Midazolam - CYP3A4 substrate

SAL statins (Sim/Ator/Lovastatin)-substrates

42
Q

Ritonavir Indication

A

Both HIV (1 and 2)

43
Q

Ritonavir SE

A

Paresthesias

44
Q

Explain why Ritonavir is often co-prescribed with other Protease inhibitors? Which HIV strain is this most useful for?

A

Ritonavir (RTV) is a PI that potently inhibits CYP3A4 –> enhances/boost exposure of other PIs –> Reduced dosing frequency/INC efficacy.

HIV2 benefits most from this

45
Q

Other than Ritonavir, name an alternative boosting agent

A

Cobicistat (used in Stribild) - has no HIV reduction activity

46
Q

How should you manage an HIV+ pt with Hypercholesterolemia on ART

A

Switch them from PTIs (if they’re on it) –> NRTIs

Remember that PTIs inhibits CYP3A4

47
Q

Raltegravir MOA

A

Binds/Inhibits Mg+ cofactors required for strand transfer during viral integration

48
Q

How can HIV develop resistance to Raltegravir

A

Mutations altering orientation of Mg+ co-factors –> Resistance of INTIs

49
Q

Raltegravir Indication

A

Combo therapy [Raltegravir + PTI + NRTI]

for naive AND experienced pts

50
Q

Raltegravir SE (3)

A

Nausea

Diarrhea

HA

51
Q

Raltegravir half life and dosage

A

9 hours (take BID after high fat meal)

52
Q

Raltegravir is the main ____ inhibitor. What’s unique about Elvitegravir?

A

Raltegravir is the main Integrase inhibitor.

Elvitegravir = short half life unboosted and is the only approved INTI that is a CYP substrate. Only in Combo pill (Stribild)

53
Q

Raltegravir is the main ____ inhibitor. What’s unique about Dolutegravir?

A

Raltegravir is the main Integrase inhibitor.

Dolutegravir = LONGEST INTI half life but is in development as microparticle injectable formulation, with half life of 3-7 weeks total

54
Q

Enfuvirtide MOA

A

Binds to [surface Gp41] –>Blocks confirmation required for fusion

55
Q

Enfuvirtide Dosage and Indication

A

Injected BID as combo therapy in [Refractory experienced pts]

56
Q

Which HIV strain is Enfuvirtide not active against and why?

A

HIV2; Mutation of binding site at [HR1 of Gp41]

57
Q

Enfuvirtide SE

A

Hypersensitivity at injection site. Cx in pts with known Hypersensitivity

58
Q

Maraviroc MOA

A

slowly and reversibly blocks [Human CCR5] interaction with [HIV Gp120] –> prevents [Tropic HIV1] attachment

59
Q

Maraviroc Indication

A

Combo therapy in [Refractory experienced pt with tropic HIV1]

60
Q

Why is a Trofile assay required when using Maraviroc? (2)

A

mutation in the [HIV Gp120-CCR5 amino acid binding sequence]

or

Emergence of CXCR4 tropic HIV

both lead to Maraviroc Resistance

61
Q

Maraviroc Contraindications (3)

A

Rifampin

Ritonavir

Liver Failure (use cautiously)

62
Q

Describe the 3 major complications of treating TB in [HIV ART pts]

A

Give RifaButin to HIV TB pts

  1. Co-admin of RifaButin (preferred TB tx in HIV pts) with ART still requires monitoring/dose adjustment
  2. Rifampin DEC efficacy of [ALL PTIs and NNRTIs] except EfaVirenz
  3. Rifamycin is a potent CYP Inducer
63
Q

Combination ART Tx for Naive patients (2)

A

[1 NNRTI (EfaVirenz > Nevirapine)] + [2 NRTI (E + T)]

OR

[1 PTI (A+R) vs. (D+R) vs. (F+ RBID)] + [2 NRTI (E+T)]

PTI boosed with RTV

64
Q

In using Combo ART for naive pts, which PTI can…

A: not be used in pts with high dose PPI

B: Not used in combo with tenofovir or [Didanosine/lamivudine]

A

A: A + R

B: Unboosted Atazanavir

65
Q

List the Dual NRTI options for [Combination ART tx in naive pts] (1 preferred and 3 Alternataive)

A
66
Q

Definition of Viral Suppression Failure (3)

A
  • HIV RNA > 400 after 24 weeks of ART
  • HIV RNA > 50 after 48 weeks of ART
  • Virologic Rebound (repeated detection of HIV RNA above undetectable even after once being suppressed)
67
Q

What is IAS-USA?

A

HIV education organization that keeps updates on Drug Resistance Mutations in HIV1

68
Q

List the 3 Combination Therapies in HIV pts that are NOT recommended? Rationale for each?

A
69
Q

What is the exception to using Non-recommended [Triple NRTI regimens] (2)

A

Z + A + L

or

Z + L + T

in pts that have worst options

70
Q

Why shouldn’t you use

PTI [Atazanavir + Indinavir]?

Any exception?

A
71
Q

Why shouldn’t you use

NRTI [Didanosine + Stavudine]?

Any exception?

A
72
Q

Why shouldn’t you use

[Double NNRTI combination tx]?

Any exception?

A
73
Q

Why shouldn’t you use

NRTI [Emtricitabine + Lamivudine]?

Any exception?

A
74
Q

Why shouldn’t you use

[Etravirine + Unboosted PTI]?

Any exception?

A
75
Q

Why shouldn’t you use

[Etravirine + (boosted ATV vs. FPV vs. TPV)]?

Any exception?

A
76
Q

Why shouldn’t you use

[Etravirine + (boosted ATV vs. FPV vs. TPV)]?

Any exception?

A
77
Q

Why shouldn’t you use

NRTI [Stavudine + Zidovudine]?

Any exception?

A
78
Q

Why shouldn’t you use

PTI [Unboosted Darunavir + Saquinaivr + Tipranavir]?

Any exception?

A
79
Q

Definition of [Functional Cure] in HIV. Example?

A

Preventing virus from inducing immune deficiency. CCR5 Zinc Fingers?

80
Q

Definition of [Sterilizing Cure] in HIV. Example?

A

Complete Elimination of Virus

Berlin Pt with stem cell transplant

🄼💊Chemotherapy/AntiViral/Botanicals (4 decks)

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