PT 1 > Block 5 - High Yield > Flashcards

Block 5 - High Yield Flashcards

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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
What is the only antifungal approved for use in pregnant women?
Amphotericin B
26
AE of Amphotericin B
1. Amphoterrible (fever, chills, spasms, vomiting, headache, hypotension) 2. Nephrotoxic 3. Hepatotoxic 4. Anemia
27
MOA of Flucytosine
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
28
What are the 3 fungi Flucytosine can treat?
1. C. neoformans 2. Cnadida 3. Chromoblastomycoses
29
What combination is used to treat Candidiasis or Cryptococcosis?
Flucytosine + Amphotericin B
30
What combination is used to treat Chromoblastomycosis?
Flucytosine + Itraconazole
31
What drug is good for treatment of cryptococcal meningitis?
Flucytosine + Amphotericin B
32
What is the cause of AE in Flucytosine?
Endogenous gut microflora express cytosine deaminase and can convert the drug to 5-flurouracil, an anti-metabolite
33
AE: bone marrow toxicity
Flucytosine
34
List the azoles in order of least to broadest spectrum of activity
Keto < Flu < Itra < Vori < Posa
35
How are the azoles involved with CYP450?
Inhibitors and substrates | Itra and Vori are most involved
36
MOA of azoles
Inhibit 14-alpha-sterol demethylase, preventing the synthesis of ergosterol and impairing growth
37
Itra and Vori should never be given with what drug and why?
Statins - rhabdomyolysis
38
AE: decreased cortisol and testosterone -> gynecomastia, libido, impotence, menstrual irregularities
Ketoconazole
39
AE: alopecia with long duration/high dose
Fluconazole
40
Good for fungal bladder infections?
Fluconazole
41
Which azole should NOT be used for Crytptococcal meningitis?
Itraconazole
42
AE: triad of HTN, hypokalemia, and peripheral edema - can cause ___ in patients with ___
Itraconazole CHF; ventricular dysfunction
43
Non-linear metabolism
Voriconazole
44
Treatment of choice for invasive aspergillus/fusarium
Voriconazole
45
AE: periostitis (bone pain), transient vision changes, photosensitivity, visual/auditory hallucinations, seizures
Voriconazole
46
Only azole active against Zygo/Mucormycosis
Posaconazole
47
First agents to directly target fungal cell wall
Echinocandins (Caspo, Mica, and Anidulafungin)
48
MOA of Echinocandins
Inhibit beta(1,3)-D-glucan synthase complex involved in synthesis of principal building block of fungal cell wall
49
What does Echinocandins NOT cover?
Cryptococcus or dimorphic fungi
50
What systemic drugs are used for cutaneous fungal infections?
Griseofulvin and Terbinafine
51
MOA of Griseofulvin
Binds to fungal microtubules, preventing formation of mitotic spindle and inhibiting mitosis; accumulates in newly differentiated keratin-producing precursor cells and prevents infection
52
MOA of terbinafine
Inhibits squalene epoxidase, which decreases ergosterol and impairs membrane function; scalene also increases, which creates toxic products
53
What is used to treat oral candidiasis (swish and swallow)?
Nystatin
54
What drug acts on DNA/RNA synthesis?
Flucytosine
55
What drugs inhibit ergosterol synthesis in the ER?
Azoles | Terbinafine
56
What drugs inhibit beta-glucan synthesis in the cell wall?
Echinocandins
57
What drugs affect the mitotic spindle?
Griseofulvin
58
What drugs affect the plasma membrane?
Amphotericin B | Nystatin
59
Which azoles penetrate the CSF?
Fluconazole and Voriconazole
60
Which azole needs a renal dose adjustment?
Fluconazole
61
TOC - cryptococcal meningitis
Fluconazole
62
TOC - invasive aspergillus/fusarium
Voriconazole
63
TOC - dermatophytes, onchomycosis
Itraconazole
64
Treatment of invasive fungal infections (Candida/Aspergillus)
Posaconazole
65
Which drug cannot be used to treat dermatophytes?
Nystatin
66
katG gene
Codes for catalase peroxidase, which activates INH in TB
67
inhA gene
Product is targeted by INH
68
MOA of INH
Catalase peroxidase activates it, and it targets the inhA gene product, which is involved in fatty acid synthesis of cell wall mycolic acid
69
AE: lupus-like reaction
INH
70
rpoB gene
Codes for RNA polymerase that is inhibited by rifampin
71
MOA of Rifampin
INhibits DNA-dependent RNA polymerase, encoded by the rpoB gene
72
AE: red discoloration of body fluids
Rifampin
73
AE: influenza syndrome
Rifampin
74
Rifampin is an ___ of menzymes.
Inducer
75
embB gene
Codes for arabinosyl transferase in TB
76
MOA of Ethambutol
Inhibits arabinosyl transferase encoded by embB gene
77
AE: optic neuritis (red-green color vision loss, etc.)
Ethambutol
78
AE: peripheral neuropathy
Ethambutol
79
pncA gene
Codes for TB pyrazinamidase
80
MOA of Pyrazinamide
Activated by TB pyrazinamidase, cidal
81
AE: hepatitis, increased serum uric acid levels
PZA
82
AE: otoxicity, nephrotoxicity
Streptomycin
83
Multi-drug resistant TB
Resistance to INH and Rifampin
84
Extensively drug resistant TB
Resistant to INH, Rifampin, FQ, injectable (amikacin, kanamycin, capreomycin)
85
INH monoresistant TB treatment
REP for 6 months
86
Ethambutol or streptomycin monoresistant B
No change
87
PZA monoresistant TB
Extend therapy to 9 months
88
Rifampin monoresistant TB
IPE for 12-18 months
89
Treatment of latent TB infection
1. INH alone, 9 months 2. Rifampin daily, 4 months 3. INH + Rifapentene, 3 months, 1/week, DOT
90
2 drugs uniquely active against NTM
Clarithro and Azithro
91
1 drug uniquely active against TB
PZA
92
Effect of hepcidin on ferroportin? Effect in chronic anemia? Effect in hemochromatosis?
Downregulates it generally Overproduced in chronic anemia, so no ferroportin means trapping of iron Underproduced, too much ferroportin, iron overload
93
3 things that are used as oral iron therapy
Ferrous sulfate, gluconate, and fumarate
94
3 things that are used as IM or IV iron therapy
Iron dextran, sucrose, gluconate
95
How is acute iron toxicity treated?
Gastric aspiration, lavage, or iron chelation
96
How is chronic iron toxicity treated?
Intermittent phlebotomy (if no anemia), iron chelation
97
Which form of folic acid is absorbed into the blood stream and where is folate stored?
Monoglutamate Liver
98
Which treatment has a black box warning for tumor progression and CV events?
EPO
99
What stimulates proliferation/differentation of myeloid cells?
G-CSF/GM-CSF
100
Name of recombinant human G-CSF
Filgrastim
101
Name of recombinant human GM-CSF
Sargramostim
102
What promotes proliferation of megakaryocytic progenitors?
IL-11 (Oprelvekin)
103
What are 2 new agents approved for treatment of ITP?
Romiplostim | Eltrombopag
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