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CPR II Exam 2 > Lecture 2: Pharm of Pulmonary Infections - Fungal > Flashcards

Lecture 2: Pharm of Pulmonary Infections - Fungal Flashcards

1
Q

MOA of Amphotericin B?

A

Complexes with ergosterol to disrupt fungal cell membrane

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2
Q

Which 3 major classes of fungi can be treated with Amphotericin B and list the 7 organisms in these classes?

A
  • Yeasts: Candida + Cryptococcus neoformans
  • Organisms causing endemic mycoses: H. capsulatum + Blastomyces dermatitidis + Coccidioides immitis
  • Pathogenic molds: Aspergillus fumigatus + agents of mucormycosis
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3
Q

What is the mechanism of resistance to Amphotericin B?

A

Alteration to ergosterol

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4
Q

What is the route of administration for Amphotericin B?

A

IV

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5
Q

What are the most common immediate and long term AE’s associated with Amphotericin B?

A
  • Immediate = FEVER, chills, muscle spasms, vomiting, HA, and hypotension
  • Long term = renal toxicity
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6
Q

What is the MOA of Flucytosine?

A

Converted to FdUMP and FUTP, which inhibit DNA and RNA synthesis, respectively

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7
Q

Which 2 organisms can be treated with Flucytosine?

A
  • C. neoformans
  • Some Candida spp.
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8
Q

What is the mechanism of resistance to Flucytosine?

A

Altered drug metabolism

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9
Q

How is Flucytosine administered?

A

Water-soluble oral form

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10
Q

What are 3 AE’s of Flucytosine?

A
  • Anemia
  • Leukopenia
  • Thrombocytopenia
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11
Q

What is the MOA of the Azoles?

A

Inhibition of fungal CYP450 enzymes –> ↓ ergosterol synthesis

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12
Q

What is the mechanism of resistance to the Azoles?

A

Upregulation of fungal CYP450 enzymes

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13
Q

What are 2 AE’s associated with the -azoles?

A
  • Minor GI issues***
  • Abnormalities in liver enzymes

*Relatively non-toxic

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14
Q

Which -azole has a greater propensity to inhibit mammalian CYP450 enzymes?

A

Ketoconazole

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15
Q

Which -azole used for fungal infections has poor CSF penetration and which has good CSF penetration?

A
  • Poor penetration = Itraconazole
  • Good penetration = Fluconazole
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16
Q

Which routes of administration exist for Itraconazole?

A

Oral and IV

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17
Q

List 6 fungi which can be treated with Itraconazole?

A
  • Dimorphic fungi: Histoplasma, Blastomyces, and Sporothrix
    • Aspergillus* spp. (largely replaced by voriconazole)
  • Dermatophytoses and onychomycosis
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18
Q

In which form does Fluconazole have the highest bioavailability and via which routes can it be given?

A
  • High oral bioavailability
  • Can be given via IV as well
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19
Q

Which 3 -azoles have the highest absorption and are more often used for systemic coverage?

A
  • Fluconazole
  • Voriconazole
  • Posaconazole
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20
Q

What is the azole of choice for cryptococcal meningitis?

A

Fluconazole

21
Q

Fluconazole is most commonly used for the treatment of what?

A

Mucocutaneous candidiasis

22
Q

Via which routes can Voriconazole be given?

A

IV and oral

23
Q

Voriconazole is an inhibitor of what?

A

Mammalian CYP3A4

24
Q

Which 3 -azoles have both oral and IV formulations?

A
  • Itraconazole
  • Fluconazole
  • Voriconazole
25
Q

What is a common AE of Voriconazole?

A

Visual disturbances

26
Q

Voriconazole has a similar spectrum to what other -azole?

A

Itraconazole

27
Q

What is the treatment of choice for invasive aspergillosis and some enviornmental molds?

A

Voriconazole

28
Q

Which -azole can be given for Candida infections, including fluconazole-resistant specices such as Candida krusei and the dimorphic fungi?

A

Voriconazole

29
Q

How is Posaconazole administered?

A

Liquid oral preparation only

30
Q

What is the only -azole with significant activity against the agents of mucormycosis?

A

Posaconazole

31
Q

Posaconazole has activity against most species of ______ and _______.

A

Posaconazole has activity against most species of Candida and Aspergillus.

32
Q

Posaconazole is currently licensed for use in what 3 situations?

A
  • Salvage therapy in invasive aspergillosis
  • Prophylaxis of fungal infections during induction chemotherapy for leukemia
  • Allogenic bone marrow transplant pt’s w/ GVHD
33
Q

What is the MOA of Echinocandins and list the 3 main drugs in this class?

A
  • Inhibit glucan synthase
  • Caspofungin, Micafungin, and Anidulafungin
34
Q

Echinocandins have activity against which 2 organisms?

A
  • Candida
  • Aspergillus
35
Q

Echinocandins are currently licensed for use in what 2 situations?

A
  • Disseminated and mucocutaneous candidal infections
  • Emperic antifungal therapy during febril neutropenia (replaced Amphotericin B)
36
Q

What is the mechanism to resistance of Echinocandins?

A

Point mutations in glucan synthase

37
Q

How are Echinocandins administered?

A

Only IV formulation

38
Q

For which organism and specific situation is the use of the Echinocandin, Caspofungin indicated?

A
  • Invasive aspergillosis
  • Only as salvage therapy in pt’s that don’t respond to amphotericin B
39
Q

The Echinocandin, Micafungin, has a specific spectrum of activity against which organisms and in which situation is it indicated?

A
  • Mucocutaneous candidiasis
  • Candidemia
  • Prophylaxis of candidal infections in bone marrow transplant pt’s
40
Q

Which anti-fungal is given for esophageal candidiasis and invasive candidiasis, includig candidemia?

A

Anidulafungin

41
Q

Which Echinocandins has the longest half-life of 24-48 hours?

A

Anidulafungin

42
Q

What is the black box warning for Flucytosine?

A

contraindicated or to be used with extreme caution in pts with:

renal impairment

pregnant/breast feeding

bone marrow depression

43
Q

The current use of glucytosine is in combination with what?

For what condition?

A

Liposomal amphotericin B

Cryptococcal meningitis

44
Q

What is the black box warning for Micafungin?

A

hepatocellular tumors

45
Q

Voriconizole has greatest affinity for which CYP?

A

CYP2C19

46
Q

What is the black box warning for itraconazole?

Waht is a common adverse effect associated with liver disease?

A

heart failure due to inotropic effects

can cause severe liver disease with intractable vomiting

47
Q

What can be seen on EKG in patients who take Fluconazole (especially when taken with drugs metabolized by CYP3A4) ?

A

QT prolongation leading to Torsades

48
Q

What is the black box warning for Amphotericin B?

Can lead to toxicity where?

A

used for treating life threatening fungal infections only

Nephrotoxicity because it has an affinity for cholesterol on human cels

49
Q

An overdose of amphotericin B can cause what cardiac issue?

A

Cardiac arrest

CPR II Exam 2 (23 decks)

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