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Block V- Pulm Antifungal Dugs Flashcards

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1
Q

Which is the broadest spectrum anti-fungal agent?

A

Which is the broadest spectrum anti-fungal agent?

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2
Q

How is Amp B administered?

A

IV only

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3
Q

What are the AE of Amp B?

A
  • Amphoterrible (infusion related fever, chills, muscle spasms, V, H, hypotension)
  • Nephrotoxic (reversible from dec. renal perfusion and irreversible from renal tubule injury w/ tubular acidosis and severe K and Mg wasting
  • Hepatotoxicity
  • Anemia
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4
Q

What is the standard therapy for life-threatening mycoses?

A

Amp B

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5
Q

What is the mechanism of action of Amp B?

A
  • binds to ergosterol in the fungal membrane

- forms a pore and increases membrane permeability

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6
Q

What organisms is Amphotericin B active against?

A
  • Candidia sp (not C. lusitaniae)
  • Cryptococcus
  • HIstoplasma
  • Blastomyces
  • Coccidiodes
  • Aspergillus
  • Fusarium
  • Zygomyces/Mucor
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7
Q

What organisms is Amphotericin B NOT active against?

A
  • Pseudallescheria boydii (Scedosporium apiosermum)

- Candidia lusitaniae

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8
Q

Explain a typical treatment scheme in systemic fungal ifnections

A
  • Amphotericin B for 4 weeks of induction therapy to reduce fungal burden
  • Azole treatment for consolidation therapy and prevention of relapse
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9
Q

Which drug is the treatment of choice for Zygomycosis/mucormycosis?

A

Amp B

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10
Q

Which drug is the only anti fungal agent that is approved for use in pregnant and breastfeeding women?

A

Amphotericin B

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11
Q

Does Flucytosine penetrate CSF?

A

Yes

used for treatment of Cryptococcal meningitis

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12
Q

Does resistance develop to Flucytosine?

A

Yes, restricts it’s use

-mutations in cytosine permease, cytosine deaminase, uracil phosphoribosyl transferase, inc. cytosine synthesis.

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13
Q

How is Flucytosine typically used clinically?

A

combo with Amp B or an Azole

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14
Q

What is the MOA of Flucytosine?

A
  • Fungistatic
  • Fungal specific cytosine deaminase
  • as 5-flurouracil can inhibit RNA synthesis (5-FUTP) and DNA synthesis (FdUMP)
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15
Q

With what drug is Amphotericin B synergistic and why?

A
  • Flucytosine

- inc. membrane permeability and so more flycytosine can enter the cell

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16
Q

Which organisms is Flucytosine active against?

A
  • Cryptococcus neoformans
  • Candida sp
  • Chromoblastomycosis (tropical climates)
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17
Q

What are AE of Flucytosine?

A
  • N/V/D
  • Bone marrow toxicity (anemia, leukopenia, thrombocytopenia)
  • Teratogenic
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18
Q

What is the order (narrow to broad) of Azole activity spectrum?

A

FIVP

Fluconazole &laquo_space;Itraconazole < Voriconazole < Posaconazole

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19
Q

Why does the Azole class have many drug interactions?

A

They are CYP450 enzyme inhibitors and substrates of CYP450

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20
Q

What is the MOA of Azole drugs?

A
  • fungistatic/fungicidal
  • inhibit 14 alpha sterol demethylase to prevent synthesis of ergosterol
  • impaired membrane function
  • inc. membrane permeability
  • dec. activity of membrane associated proteins
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21
Q

What are AE of ALL Azoles?

A
  • GI distress
  • Hepatotoxicity
  • Teratogenic
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22
Q

Most drug interactions are associated with which azole drugs?

A

Itraconazole and Voriconazole

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23
Q

What are some example of drug interactions with azole drugs?

A
  • Statins
  • cyclosporins
  • Benzodiazepiens
  • HIV protease inhibitors
  • warfarin
  • digoxin
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24
Q

What will happen if you give a patient taking a Statin Itraconazole or Voriconazole?

A

Rhabodomyolysis! Never do this!

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25
What is the spectrum of activity of Ketoconazole?
-Candidia , C neoformans Coccidiodes, Histoplasma, Blastomyces -dermatophytes
26
Does ketoconazole reach CSF or urine?
no
27
What are AE of Ketoconazole?
- inhibits Adrenal and Gonadal steroid synth - Dec. cortisol and testosterone - gyencomastia, libido, impotence, menstraul iregularities, hypotension, fatigue
28
Does Flucanazole reach the CSF?
Excellently so!
29
What are AE of FLucanazole?
-alopecia N/V/ skin rash GI issues
30
Which drug is used to treat fungal bladder infections?
Fluconazole
31
Which organisms are Fluconazole active against?
- Candidia - used for mucocutaneous candiasis - not C. Glabrata or krusei Crytpococcal (meningitis) Coccidiodes less activity with histoplasmosis , blastomycosis, Sporotrichosis
32
T or F? Itraconazole can penetrate the CSF, urine, and eye
false. | ineffective treatment of meningitis or bladder infections
33
Itraconazole is a strong inhibitor of which enzyme?
CYP3A4
34
Which organisms are Itraconazole active against?
Dermatophyte and Onchomycosis Candida NOT Cryptococcal meningitis Non meningeal Blastomyces, Histoplasmosis, Sporothrix, Coccidiodomycosis Aspergillus Some activity to Pseudoallerischeri Boydii/ Scedosporium
35
What are AE of Itraconazole?
- Hypertension, hypokalemia, peripheral edema - CHF in pts with ventricular dysfunction - do not give to pts. with ventricular dysfunction or CHF
36
Where is Voriconazole distributed?
widely | includes CSF
37
Describe the metabolism of Voriconazole - hepatic - non linear
- hepatic | - non linear
38
Voriconazole inhibits which enzymes?
CYP2C19, 2C9, 3A4
39
What organisms is Voriconazole active against
- Candidia - Endemic dimorphic fungal infections (histo, blasto, Sporo, coccidio ) - Pseduoallerischeri Boydii/Scedosporim - Asperigillus and Fusarium
40
Which drug is the treatment of choice for invasive Aspergillus spp. ?
Voriconazole
41
What are AE of Voriconazole ?
- Periostitis - Vision changes (flashes of light and changes of color) - Photosensitivity/Rash - Rarely steven johnson syndrom - Visual/auditory hallucination - seizures
42
What is the distribution of Posaconazole?
- tissues | - poor to CSF and urine
43
How is Posocanoazole eliminated?
fecal
44
Which enzyme does Posaconazole inhibit?
-CYP3A4
45
Against which organisms is Posaconazole active?
- Dermatophytes - Candidia - Endemic dimorphic fungal infections (histo, blasto, Sporo, coccidio ) - Pseduoallerischeri Boydii/Scedosporim - Asperigillus and Fusarium - Zygomycosis/ Murcomycosis
46
Which Azole has activity against Zygomycosis and Murcomycosis?
Posaconazole
47
Which drug is used for anti fungal prophylaxis in pts with prolong neutorpenia or graft vs. host dz?
Posaconazole
48
What are examples of drugs from the Echinocandin class?
Caspofungin Micafungin Anidulafungin
49
Do Echinocandins penetrate the CSF?
no
50
What are AE of Echinocandins?
- rapid infusion leads to histamine like effect and skin itching - Embryotoxic
51
What is the MOA of Echinocandins?
- inhibit B (1,3)-D-glucan synthase complex that is involved in the biosynthesis of the principal building block of the fungal cell wall - impairs structural integrity of cell wall - increases osmotic instability --> cell death
52
Against which organisms is Echinocandin active?
- Candida spp (glabrata and kruesi) - invasive Candida (fungicidal) - Aspergillus sp (fungistatic)
53
Which drugs can be used systemically for the infection of dermatophytes?
Griseofulvin | Terbinafine
54
What is the MOA of Griseofulvin?
- fungistatic - binds fungal microtubules, prevents formation of mitotic spindle - inhibits fungus mitosis - infected cells exfoliated eventually
55
Where does Griseofulvin accumulate?
newly differentiated keratin producing precursor cells | hair, skin, nails
56
How long is the course of treatment of Griseofulvin?
until all tissue is replaced by new tissue | greater than 6 months
57
what are the AE of Griseofulvin?
- HA/ lethargy, vertigo, blurred vision - Utricaria, photosensitivity, rash, skin eruptions - Heptatotoxic - leukopenia, neutropenia, monocytosis - fetal abnormalities
58
What are the drug interactions of Griseofulvin?
CYP450 enzyme inducer | -warfarin and oral contraceptive interactions
59
Where is oral Terbinafine deposited?
skin, nails, hair, fat
60
Explain terbinafine metabolism
liver metabolism significant first pass metabolism excreted renal
61
What is the spectrum of activity of oral Terbinafine?
- dermatophytes | - Candida albicans
62
What are AE of Terbinafine?
GI distress, HA, rash | -hepatotoxicity, neutropenai, Steven Johnson (rare)
63
What is the MOA of Terbinafine?
inhibits fungal Squalene epoxidase - inc. squalene is toxic - Cannot produce ergosterol so impaired fungal membrane function
64
What are examples of topical Azoles?
Clotrimazole Miconazole Terconazole
65
What is the MOA of Nystatin ?
binds to ergosterol and forms pores in the fungal membrane
66
Why is Nystatin not available in IV form?
too toxic
67
What is the spectrum of activity of Nystatin?
oral candidasis | -swish and swallow treatment
68
What are the uses of topical azoles?
- oral and vulvovaginal candidasis | - dermatophyte infections
69
What are examples of topical Allylamines?
- Terbinafine | - Naftifine
70
What are examples of oral Benzylamines?
Butenafine
71
What is the MOA of topical Allylamine and Benzylamines
-inhibit squalene epoxidase
72
What is the spectrum of activity of topical Terbinafine, Naftifine, and Butenafine?
- candida albicans | - Dermatophytes
73
What are the clinical uses of topical Terbinafine, Naftifine, and Butenafine?
tinea crusis, tinea corporis, tinea pedis

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