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Pharm > Block V- Pulm Antifungal Dugs > Flashcards

Block V- Pulm Antifungal Dugs Flashcards

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
Q

What is the spectrum of activity of Ketoconazole?

A

-Candidia , C neoformans
Coccidiodes, Histoplasma, Blastomyces
-dermatophytes

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26
Q

Does ketoconazole reach CSF or urine?

A

no

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27
Q

What are AE of Ketoconazole?

A
  • inhibits Adrenal and Gonadal steroid synth
  • Dec. cortisol and testosterone
  • gyencomastia, libido, impotence, menstraul iregularities, hypotension, fatigue
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28
Q

Does Flucanazole reach the CSF?

A

Excellently so!

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29
Q

What are AE of FLucanazole?

A

-alopecia
N/V/
skin rash
GI issues

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30
Q

Which drug is used to treat fungal bladder infections?

A

Fluconazole

31
Q

Which organisms are Fluconazole active against?

A
  • Candidia
  • used for mucocutaneous candiasis
  • not C. Glabrata or krusei

Crytpococcal (meningitis)

Coccidiodes

less activity with histoplasmosis , blastomycosis, Sporotrichosis

32
Q

T or F? Itraconazole can penetrate the CSF, urine, and eye

A

false.

ineffective treatment of meningitis or bladder infections

33
Q

Itraconazole is a strong inhibitor of which enzyme?

A

CYP3A4

34
Q

Which organisms are Itraconazole active against?

A

Dermatophyte and Onchomycosis

Candida

NOT Cryptococcal meningitis

Non meningeal Blastomyces, Histoplasmosis, Sporothrix, Coccidiodomycosis

Aspergillus

Some activity to Pseudoallerischeri Boydii/ Scedosporium

35
Q

What are AE of Itraconazole?

A
  • Hypertension, hypokalemia, peripheral edema
  • CHF in pts with ventricular dysfunction
  • do not give to pts. with ventricular dysfunction or CHF
36
Q

Where is Voriconazole distributed?

A

widely

includes CSF

37
Q

Describe the metabolism of Voriconazole

  • hepatic
  • non linear
A
  • hepatic

- non linear

38
Q

Voriconazole inhibits which enzymes?

A

CYP2C19, 2C9, 3A4

39
Q

What organisms is Voriconazole active against

A
  • Candidia
  • Endemic dimorphic fungal infections (histo, blasto, Sporo, coccidio )
  • Pseduoallerischeri Boydii/Scedosporim
  • Asperigillus and Fusarium
40
Q

Which drug is the treatment of choice for invasive Aspergillus spp. ?

A

Voriconazole

41
Q

What are AE of Voriconazole ?

A
  • Periostitis
  • Vision changes (flashes of light and changes of color)
  • Photosensitivity/Rash
  • Rarely steven johnson syndrom
  • Visual/auditory hallucination
  • seizures
42
Q

What is the distribution of Posaconazole?

A
  • tissues

- poor to CSF and urine

43
Q

How is Posocanoazole eliminated?

A

fecal

44
Q

Which enzyme does Posaconazole inhibit?

A

-CYP3A4

45
Q

Against which organisms is Posaconazole active?

A
  • Dermatophytes
  • Candidia
  • Endemic dimorphic fungal infections (histo, blasto, Sporo, coccidio )
  • Pseduoallerischeri Boydii/Scedosporim
  • Asperigillus and Fusarium
  • Zygomycosis/ Murcomycosis
46
Q

Which Azole has activity against Zygomycosis and Murcomycosis?

A

Posaconazole

47
Q

Which drug is used for anti fungal prophylaxis in pts with prolong neutorpenia or graft vs. host dz?

A

Posaconazole

48
Q

What are examples of drugs from the Echinocandin class?

A

Caspofungin
Micafungin
Anidulafungin

49
Q

Do Echinocandins penetrate the CSF?

A

no

50
Q

What are AE of Echinocandins?

A
  • rapid infusion leads to histamine like effect and skin itching
  • Embryotoxic
51
Q

What is the MOA of Echinocandins?

A
  • 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
Q

Against which organisms is Echinocandin active?

A
  • Candida spp (glabrata and kruesi)
  • invasive Candida (fungicidal)
  • Aspergillus sp (fungistatic)
53
Q

Which drugs can be used systemically for the infection of dermatophytes?

A

Griseofulvin

Terbinafine

54
Q

What is the MOA of Griseofulvin?

A
  • fungistatic
  • binds fungal microtubules, prevents formation of mitotic spindle
  • inhibits fungus mitosis
  • infected cells exfoliated eventually
55
Q

Where does Griseofulvin accumulate?

A

newly differentiated keratin producing precursor cells

hair, skin, nails

56
Q

How long is the course of treatment of Griseofulvin?

A

until all tissue is replaced by new tissue

greater than 6 months

57
Q

what are the AE of Griseofulvin?

A
  • HA/ lethargy, vertigo, blurred vision
  • Utricaria, photosensitivity, rash, skin eruptions
  • Heptatotoxic
  • leukopenia, neutropenia, monocytosis
  • fetal abnormalities
58
Q

What are the drug interactions of Griseofulvin?

A

CYP450 enzyme inducer

-warfarin and oral contraceptive interactions

59
Q

Where is oral Terbinafine deposited?

A

skin, nails, hair, fat

60
Q

Explain terbinafine metabolism

A

liver metabolism
significant first pass metabolism

excreted renal

61
Q

What is the spectrum of activity of oral Terbinafine?

A
  • dermatophytes

- Candida albicans

62
Q

What are AE of Terbinafine?

A

GI distress, HA, rash

-hepatotoxicity, neutropenai, Steven Johnson (rare)

63
Q

What is the MOA of Terbinafine?

A

inhibits fungal Squalene epoxidase

  • inc. squalene is toxic
  • Cannot produce ergosterol so impaired fungal membrane function
64
Q

What are examples of topical Azoles?

A

Clotrimazole
Miconazole
Terconazole

65
Q

What is the MOA of Nystatin ?

A

binds to ergosterol and forms pores in the fungal membrane

66
Q

Why is Nystatin not available in IV form?

A

too toxic

67
Q

What is the spectrum of activity of Nystatin?

A

oral candidasis

-swish and swallow treatment

68
Q

What are the uses of topical azoles?

A
  • oral and vulvovaginal candidasis

- dermatophyte infections

69
Q

What are examples of topical Allylamines?

A
  • Terbinafine

- Naftifine

70
Q

What are examples of oral Benzylamines?

A

Butenafine

71
Q

What is the MOA of topical Allylamine and Benzylamines

A

-inhibit squalene epoxidase

72
Q

What is the spectrum of activity of topical Terbinafine, Naftifine, and Butenafine?

A
  • candida albicans

- Dermatophytes

73
Q

What are the clinical uses of topical Terbinafine, Naftifine, and Butenafine?

A

tinea crusis, tinea corporis, tinea pedis

Pharm (9 decks)

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