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BIIC Cancers and Pharmo > Opportunistic Disease Therapies > Flashcards

Opportunistic Disease Therapies Flashcards

1
Q

HIV therapy is a ___________ therapy.

A

life-long

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2
Q

Goals of Antiretroviral Therapy (2)

A
  1. decrease viral load over time

2. restore and preserve immunological function

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3
Q

Treatment w/ ART promotes? (3)

A
  1. enhanced survival
  2. decreased morbidity
  3. reduced risk of transmission
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4
Q

What is essential to the effectiveness of treatment with ART?

A

patient adherence

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5
Q

What are the five classes of antiretroviral drugs?

A
  1. NRTIs: Nucleoside/tide reverse transcriptase inhibitors
  2. NNRTIs: Nonnucleoside reverse transcriptase inhibitors
  3. PIs: Protease inhibitors
  4. FIs: Fusion/Entry inhibitors
  5. INSTIs: Integrase inhibitors
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6
Q

Which CYP protein is taken advantage of by pharmacokinetic boosters to increase protease inhibitor levels? What drugs are used to do this?

A
  1. CYP450

2. ritonavir and cobicistat

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7
Q

Initial Therapy for HIV

A

2 NRTIs w/ one of the following:

  • integrase inhibitors
  • NNRTIs
  • PI boosted w/ CYP450 inhibitor ritonavir/cobicistat
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8
Q

Common Regimens are formulated into __________

A

single tablet, fixed-dose

*not all cases of HIV can be treated as a coformulation

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9
Q

What are the three main initial regimens used in HIV patients?

A
  1. bictegravir/tenofovir alafenamide/emitricitabine
  2. Raltegravir plus tenofovir/emtricitabine
  3. Dolutegravir plus tenofovir/emtricitabine
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10
Q

What is the primary initial treatment given to a pt w/ HIV that is HLA-B*5701 negative?

A

dolutegravir/abacavir/lamivudine

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11
Q

Conditions when you should proceed with caution (5)

A
  1. low CD4 cell count
  2. high HIV RNA load
  3. positive for 5701 allele of human leukocyte antigen
    4, the presence of other medical condition/coinfection
  4. pregnancy (NOT contraindication)
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12
Q

Choice of second-line therapy depends on reason that first-line therapy failed (3)

A
  1. poor pt adherence
  2. drug-resistant strain
  3. suboptimal drug factors
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13
Q

What are fixes that can be made if first-line therapy is ineffective?

A
  1. boosted PI
  2. add/change INTSI and/or NRIs
  3. refer to current guidelines
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14
Q

How often should you dose with oral formulation?

A

once a day

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15
Q

Common ADRs of MOST antiretrovirals (6)

A
  • headaches
  • nausea
  • vomiting
  • diarrhea
  • hepatotoxicity
  • myelosuppression
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16
Q

Most antiretrovirals are metabolized/inhibited by _______

A

CYP enzymes

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17
Q

What are NRTIs?

A

nucleotide analogs

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18
Q

What are the prodrugs of tenofovir? (2)

A
  1. tenofovir alafenamide

2. tenofovir disoproxill fumarate

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19
Q

Because all NRTIs competitively inhibit reverse transcriptase, they are effective against HIV-

A

1 and 2

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20
Q

What are the thymine analogs? (2)

A

zidovudine and stavudine

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21
Q

What are the cytosine analogs? (2)

A

emtricitabine and lamivudine

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22
Q

What are the adenosine analogs? (2)

A

didanosine and tenofovir

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23
Q

What is the guanosine analog? (1)

A

abacavir

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24
Q

NRTIs are not activated until ________________?

A

they are phosphorylated by cellular machinery–> become the activated triphosphate form

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25
Q

Activated NRTIs lead to … (2)

A
  1. inhibition of binding w/ incoming nucleotide

2. Premature chain termination

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26
Q

Because NRTIs accumulate in all dividing cells in the body, _________ events can occur.

A

toxic; they inhibit reverse transcriptase more potently than human DNA polymerases

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27
Q

NRTI ADRs

A
  • mitochondrial toxicity risk: peripheral neuropathy, pancreatitis, lipoatrophy, hepatic steatosis
  • lactic acidosis: look for high aminotransferase, progressive hepatomegaly, metabolic acidosis of unknown cause
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28
Q

Lipoatrophy and insulin resistance occur most frequently in what two NRTIs?

A

stavudine and zidovudine

29
Q

How are NRTIs excreted?

A

renal excretion of parent or conjugated compound

30
Q

Inihibit reverse transcriptase but are NOT structurally related to nucleosides/tides

A

NNRTIs: non-nucleoside reverse transcriptase inhibitors

31
Q

Are NNRTIs strain specific?

A

yes

32
Q

What is the main limitation of NNRTIs?

A

resistance develops rapidly–> NEVER use as a single agent in monotherapy or as an add on to failing therapy
*cross-resistance w/ other NNRTIs occurs

33
Q

NNRTI MOA

A

binds to a non-active site on reverse transcriptase–> drug-induced conformational change–> reduced activity of reverse transcriptase (negative allosteric modulation)
*no activity against host DNA polymerases

34
Q

NNRTI ADRs

A
  • hypersensitivity reactions (includes rash)
  • dizziness
  • neuropsychiatric effects(efavirenz)
35
Q

What are the NNRTIs? (5)

A
  1. efavirenz
  2. nevirapine
  3. delavirdine
  4. etravirine
  5. rilpivirine
36
Q

What is one easy way to increase absorption of NNRTIs?

A

take with food

37
Q

Plasma protein binding for NNRTIs is ____

A

moderate to high

38
Q

How are NNRTIs metabolized

A

hepatically–> many induce CYPs, the potential for DDI is high

39
Q

What are the 2 fusion inhibitors?

A

maraviroc and enfuvirtide

*created due to some individuals exposed to HIV that didn’t get AIDS–> DELETION of CCR5 gene

40
Q

Maraviroc (oral): CYP? Eliminated? ADRs?

A
  • CYP3A4
  • feces; 20% renally
  • hepatotoxicity sometimes preceded by fever/rash, URI
41
Q

Enfuvirtide(subQ): MOA? When is it used? Metabolized? ADRs?

A
  • Binds HIV-1 protein gp41 = prevents conformational change needed for HIV to gain entrance into cell
  • Indicated: treatment-experienced pts w/ evidence of viral replication despite ongoing therapy
  • metabolized: proteolytic hydrolysis
  • pain, erythema, induration, nodules(all pts)
42
Q

Protease Inhibitors MOA

A

reversible inhibitors of HIV aspartyl protease = prevents cleaving of HIV proteins necessary for replication, maturity, and release

43
Q

PI Indication

A

pts w/ uncertainties

44
Q

PIs:

A
  • atazanavir and darunavir most commonly prescribed

- all others end in -avir

45
Q

PIs ADRs

A
  • nausea
  • diarrhea
  • abdominal discomfort
  • vomiting
  • glucose/lipid metabolism issues = insuline resistance
  • fat redistribution = buffalo hump
46
Q

Food _______ absorption of PI

A

increases

47
Q

PI Elimination?

A

CYPs

48
Q

DDIs are ____________ for pts taking PIs

A

a significant concern

49
Q

PI DDIs

A

inhibitors of CYP450

50
Q

PI DDIs: simvastatin and lovastatin

A

rhabdo

51
Q

PI DDIs: midazolam and triazolam

A

excessive sedation

52
Q

PI DDIs: fentanyl

A

respiratory depression

53
Q

PI DDIs: rifampin, St. John’s Wort

A

treatment failure due to induction of the CYPs

54
Q

PI DDI Cautions

A

warfarin, sildenafil, phenytoin

55
Q

Ritonavir Pharmacokinetics

A
  • CYP3A4 inhibitor, CYP2D6

- low dose of ritonavir can be used to elevate levels of second PI

56
Q

Cobicistat Pharmacokinetics

A
  • inhibits CYP3A4, CYP3A isozymes, CYP2D6, and P-gp
  • used to increase the bioavailability of atazanavir and darunavir
  • increases serum creatinine
57
Q

Integrase strand transfer inhibitors/INSTIs: what do they do?

A
  • prevent the incorporation of HIV DNA into host genome
  • first-line agents for newly diagnosed
  • change to prevent infection after exposure if given immediately
58
Q

What should be avoided while taking INSTIs?

A

antacids and other polyvalent cations (dairy)

59
Q

INSTI: Raltegravir ADR?

A

rare but life-threatening rhabdo

60
Q

INSTI: Bictegravir only available as coformulation tablet: dosing? Elimination? ADRs?

A
  • daily dosing w/ food
  • eliminated through glucuronidation and CYP
  • nausea and diarrhea
61
Q

INSTI class-wide ADR:

A

teratogenic: neural tube defects

62
Q

In 2015 _____% of people were UNAWARE OF THEIR INFECTION

A

15

63
Q

First indication of HIV?

A

opportunistic infections

64
Q

In 2015 _____% of newly diagnosed hadn’t been linked to care w/n 3 mo

A

16

65
Q

only about 49% of pts were effectively linked to care AND had durable viral suppression

A

likely due to poor adherence, unfavorable pharmacokinetics, or unexplained biologic factors

66
Q

untreated pts survive ________ after initial manifestation of AIDS

A

1-2 yrs

67
Q

What is the main principle of OI management?

A

treatment of HIV to restore fxnal immune system

68
Q

6 Things to prevent OIs

A
  1. prevent exposure
  2. vaccinate
  3. use chemoprophylaxis to prevent first-episode disease
  4. treat emergent OI
  5. secondary chemoprophylaxis to prevent disease recurrence
  6. Discontinue prophylaxes w/ sustained ART
69
Q

Immune Reconstitution Inflammatory Syndrome

A

inflammatory rxns that appear associate w/ immune reconstitution

  • may be due to rapid increase in CD4 count
  • fever, sweats, chills, malaise
  • TB: paradoxical symptoms
  • Mycobacterium Avium Complex: suppurative lymphadenitis
  • Meningitis: increased intracranial pressure
  • keep using ARTs, if severe enough may need to use corticosteroids

BIIC Cancers and Pharmo (10 decks)

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