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PT 1 > Block 5 - High Yield > Flashcards

Block 5 - High Yield Flashcards

1
Q

Triple drug regiment for maintenance immunotherapy

A
  1. Glucocorticoid
  2. Anti-proliferative
  3. Cyclosporin or tacrolimus
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2
Q

AE: Cytokine release syndrome

A

rATG and Alemtuzumab

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3
Q

This drug is humanized anti-CD52 and actively depletes T cells

A

Ametuzumab

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4
Q

This drug is a humanized antibody that binds CD25 and inhibits T cell proliferation

A

Basiliximab

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5
Q

MOA of Azathioprine

A

Azathioprine -> 6-mercaptopurine -> 6-TIMP (inhibits de novo purine biosynthesis) -> 6-TGTP (inhibits CD28/Rac1 T cell costimulation) -> incorporated into DNA -> apoptosis

Inhibition of lymphocyte proliferation

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6
Q

These drugs interact with azothioprine and increase toxicity

A

Allopurinol and Febuxostat (gout) -> inhibit xanthine oxidase

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7
Q

MOA of mycophenolate mofetil (MMF)

A

Converted by plasma esterases to mycophenolic acid, which inhibits IMPDH type II, which is required for the S phase of the cell cycle of de novo purine synthesis

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8
Q

AE: progressive multifocal leukoencephalopathy (and what causes it?)

A
  1. Mycophenolate mofetil
  2. Natalizumab

Reactivation of JC virus

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9
Q

Which anti-proliferative is safe to use in pregnant women?

A

Azathioprine

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10
Q

MOA of cyclosporine and tacrolimus

A

Diffuse into cell -> cyclosporin binds to cyclophilin and tacrolimus binds to FKBP -> inhibit calcineurin, preventing it from dephosphorylating NFAT, a TF that allows IL-2 to be produced

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11
Q

Which drugs inhibit signal 1 of T cell activation? Which drugs inhibit signal 2?

A

Signal 1: cyclosporine/tacrolimus

Signal 2: sirolimus/everolimus

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12
Q

AE: nephrotoxicity and hypertension

A

Cyclosporine/tacrolimus

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13
Q

MOA of sirolimus and everolimus

A

Bind FKBP, inhibit mTOR, which normally regulates protein synthesis, cell proliferation, and survival downstream of IL-2 binding to its receptor

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14
Q

What types of transplants are sirolimus and everolimus not recommended for and why?

A
  1. Liver transplant (risk of hepatic artery thrombosis)

2. Lung transplant (risk of anastomotic dehiscence)

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15
Q

MOA of Ipilimumab

A
  1. Binds to CTLA4
  2. Prevents CTLA4 from binding to CD 80/86 and from delivering a negative signal
  3. Leaves CD 28 co-stimulation intact
  4. Leads to enhanced T cell activation
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16
Q

What is Ipilimumab use to treat?

A

Late stage melanoma

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17
Q

What are Pembrolizumab and Nivolumab used to treat?

A

Aggressive metastatic cancers

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18
Q

MOA of Pembrolizumab and Nivolumab

A
  1. Bind to PD1 protein on T-cells
  2. Prevent inhibition of T-cell by PD-L1 (found on tumor cells)
  3. Maintain T cell activation
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19
Q

AE: bradyarrythmia, AV block, varicella zorster virus infection

A

Fingolimid

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20
Q

___ have many drug interactions due to being metabolized by CYP3A4.

A

Calcineurin inhibitors (cyclopsorine and tacrolimus)

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21
Q

Broadest spectrum anti-fungal agent

A

Amphotericin B

Not active against C. lusitaniae, Pseudallescheria boydii

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22
Q

What is Amphotericin B first-line treatment for?

A

Life-threatening mycotic infections

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23
Q

MOA of Amphotericin B

A

Binds to Ergosterol, forms a pore in the membrane, increases permeability, efflux of essential molecules, cell death

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24
Q

How is Amphotericin used?

A

Initial induction therapy (4 weeks) to reduce fungal burden, replaced azoles for consolidation therapy

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25
Q

What is the only antifungal approved for use in pregnant women?

A

Amphotericin B

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26
Q

AE of Amphotericin B

A
  1. Amphoterrible (fever, chills, spasms, vomiting, headache, hypotension)
  2. Nephrotoxic
  3. Hepatotoxic
  4. Anemia
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27
Q

MOA of Flucytosine

A

Taken up into cell through a cytosine permease, converted to 5-flurouracil (with cytosine deaminase) -> 5-FUTP (inhibits RNA synthesis) and 5-FdUMP (inhibits thymidylate synthase, which inhibits DNA synthesis)

Fungistatic

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28
Q

What are the 3 fungi Flucytosine can treat?

A
  1. C. neoformans
  2. Cnadida
  3. Chromoblastomycoses
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29
Q

What combination is used to treat Candidiasis or Cryptococcosis?

A

Flucytosine + Amphotericin B

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30
Q

What combination is used to treat Chromoblastomycosis?

A

Flucytosine + Itraconazole

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31
Q

What drug is good for treatment of cryptococcal meningitis?

A

Flucytosine + Amphotericin B

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32
Q

What is the cause of AE in Flucytosine?

A

Endogenous gut microflora express cytosine deaminase and can convert the drug to 5-flurouracil, an anti-metabolite

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33
Q

AE: bone marrow toxicity

A

Flucytosine

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34
Q

List the azoles in order of least to broadest spectrum of activity

A

Keto < Flu < Itra < Vori < Posa

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35
Q

How are the azoles involved with CYP450?

A

Inhibitors and substrates

Itra and Vori are most involved

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36
Q

MOA of azoles

A

Inhibit 14-alpha-sterol demethylase, preventing the synthesis of ergosterol and impairing growth

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37
Q

Itra and Vori should never be given with what drug and why?

A

Statins - rhabdomyolysis

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38
Q

AE: decreased cortisol and testosterone -> gynecomastia, libido, impotence, menstrual irregularities

A

Ketoconazole

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39
Q

AE: alopecia with long duration/high dose

A

Fluconazole

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40
Q

Good for fungal bladder infections?

A

Fluconazole

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41
Q

Which azole should NOT be used for Crytptococcal meningitis?

A

Itraconazole

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42
Q

AE: triad of HTN, hypokalemia, and peripheral edema - can cause ___ in patients with ___

A

Itraconazole

CHF; ventricular dysfunction

43
Q

Non-linear metabolism

A

Voriconazole

44
Q

Treatment of choice for invasive aspergillus/fusarium

A

Voriconazole

45
Q

AE: periostitis (bone pain), transient vision changes, photosensitivity, visual/auditory hallucinations, seizures

A

Voriconazole

46
Q

Only azole active against Zygo/Mucormycosis

A

Posaconazole

47
Q

First agents to directly target fungal cell wall

A

Echinocandins (Caspo, Mica, and Anidulafungin)

48
Q

MOA of Echinocandins

A

Inhibit beta(1,3)-D-glucan synthase complex involved in synthesis of principal building block of fungal cell wall

49
Q

What does Echinocandins NOT cover?

A

Cryptococcus or dimorphic fungi

50
Q

What systemic drugs are used for cutaneous fungal infections?

A

Griseofulvin and Terbinafine

51
Q

MOA of Griseofulvin

A

Binds to fungal microtubules, preventing formation of mitotic spindle and inhibiting mitosis; accumulates in newly differentiated keratin-producing precursor cells and prevents infection

52
Q

MOA of terbinafine

A

Inhibits squalene epoxidase, which decreases ergosterol and impairs membrane function; scalene also increases, which creates toxic products

53
Q

What is used to treat oral candidiasis (swish and swallow)?

54
Q

What drug acts on DNA/RNA synthesis?

A

Flucytosine

55
Q

What drugs inhibit ergosterol synthesis in the ER?

A

Azoles

Terbinafine

56
Q

What drugs inhibit beta-glucan synthesis in the cell wall?

A

Echinocandins

57
Q

What drugs affect the mitotic spindle?

A

Griseofulvin

58
Q

What drugs affect the plasma membrane?

A

Amphotericin B

Nystatin

59
Q

Which azoles penetrate the CSF?

A

Fluconazole and Voriconazole

60
Q

Which azole needs a renal dose adjustment?

A

Fluconazole

61
Q

TOC - cryptococcal meningitis

A

Fluconazole

62
Q

TOC - invasive aspergillus/fusarium

A

Voriconazole

63
Q

TOC - dermatophytes, onchomycosis

A

Itraconazole

64
Q

Treatment of invasive fungal infections (Candida/Aspergillus)

A

Posaconazole

65
Q

Which drug cannot be used to treat dermatophytes?

66
Q

katG gene

A

Codes for catalase peroxidase, which activates INH in TB

67
Q

inhA gene

A

Product is targeted by INH

68
Q

MOA of INH

A

Catalase peroxidase activates it, and it targets the inhA gene product, which is involved in fatty acid synthesis of cell wall mycolic acid

69
Q

AE: lupus-like reaction

70
Q

rpoB gene

A

Codes for RNA polymerase that is inhibited by rifampin

71
Q

MOA of Rifampin

A

INhibits DNA-dependent RNA polymerase, encoded by the rpoB gene

72
Q

AE: red discoloration of body fluids

73
Q

AE: influenza syndrome

74
Q

Rifampin is an ___ of menzymes.

75
Q

embB gene

A

Codes for arabinosyl transferase in TB

76
Q

MOA of Ethambutol

A

Inhibits arabinosyl transferase encoded by embB gene

77
Q

AE: optic neuritis (red-green color vision loss, etc.)

A

Ethambutol

78
Q

AE: peripheral neuropathy

A

Ethambutol

79
Q

pncA gene

A

Codes for TB pyrazinamidase

80
Q

MOA of Pyrazinamide

A

Activated by TB pyrazinamidase, cidal

81
Q

AE: hepatitis, increased serum uric acid levels

82
Q

AE: otoxicity, nephrotoxicity

A

Streptomycin

83
Q

Multi-drug resistant TB

A

Resistance to INH and Rifampin

84
Q

Extensively drug resistant TB

A

Resistant to INH, Rifampin, FQ, injectable (amikacin, kanamycin, capreomycin)

85
Q

INH monoresistant TB treatment

A

REP for 6 months

86
Q

Ethambutol or streptomycin monoresistant B

87
Q

PZA monoresistant TB

A

Extend therapy to 9 months

88
Q

Rifampin monoresistant TB

A

IPE for 12-18 months

89
Q

Treatment of latent TB infection

A
  1. INH alone, 9 months
  2. Rifampin daily, 4 months
  3. INH + Rifapentene, 3 months, 1/week, DOT
90
Q

2 drugs uniquely active against NTM

A

Clarithro and Azithro

91
Q

1 drug uniquely active against TB

92
Q

Effect of hepcidin on ferroportin? Effect in chronic anemia? Effect in hemochromatosis?

A

Downregulates it generally

Overproduced in chronic anemia, so no ferroportin means trapping of iron

Underproduced, too much ferroportin, iron overload

93
Q

3 things that are used as oral iron therapy

A

Ferrous sulfate, gluconate, and fumarate

94
Q

3 things that are used as IM or IV iron therapy

A

Iron dextran, sucrose, gluconate

95
Q

How is acute iron toxicity treated?

A

Gastric aspiration, lavage, or iron chelation

96
Q

How is chronic iron toxicity treated?

A

Intermittent phlebotomy (if no anemia), iron chelation

97
Q

Which form of folic acid is absorbed into the blood stream and where is folate stored?

A

Monoglutamate

Liver

98
Q

Which treatment has a black box warning for tumor progression and CV events?

99
Q

What stimulates proliferation/differentation of myeloid cells?

A

G-CSF/GM-CSF

100
Q

Name of recombinant human G-CSF

A

Filgrastim

101
Q

Name of recombinant human GM-CSF

A

Sargramostim

102
Q

What promotes proliferation of megakaryocytic progenitors?

A

IL-11 (Oprelvekin)

103
Q

What are 2 new agents approved for treatment of ITP?

A

Romiplostim

Eltrombopag

PT 1 (34 decks)

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