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

Lecture 2: Pharm of Pulmonary Infections - Fungal Flashcards

(49 cards)

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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?

21
Q

Fluconazole is most commonly used for the treatment of what?

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A

Mucocutaneous candidiasis

22
Q

Via which routes can Voriconazole be given?

23
Q

Voriconazole is an inhibitor of what?

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A

Mammalian CYP3A4

24
Q

Which 3 -azoles have both oral and IV formulations?

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A
  • Itraconazole
  • Fluconazole
  • Voriconazole
25
What is a common AE of Voriconazole?
**V**isual disturbances
26
Voriconazole has a similar spectrum to what other -azole?
Itraconazole
27
What is the treatment of choice for **invasive aspergillosis** and some enviornmental molds?
Voriconazole
28
Which -azole can be given for *Candida* infections, including **fluconazole-resistant specices** such as *Candida krusei* and the dimorphic fungi?
Voriconazole
29
How is Posaconazole administered?
**Liquid oral** preparation **only**
30
What is the only -azole with **significant activity** against the agents of **mucormycosis**?
Posaconazole
31
Posaconazole has activity against most species of ______ and \_\_\_\_\_\_\_.
Posaconazole has activity against most species of ***Candida*** and ***Aspergillus***.
32
Posaconazole is currently licensed for use in what 3 situations?
- **Salvage therapy** in **invasive aspergillosis** - **Prophylaxis** of fungal infections during **induction chemotherapy** for **leukemia** - **Allogenic bone marrow transplant** pt's w/ **GVHD**
33
What is the MOA of Echinocandins and list the 3 main drugs in this class?
- Inhibit **glucan synthase** - Caspo**fungin**, Mica**fungin**, and Anidula**fungin**
34
Echinocandins have activity against which 2 organisms?
- *Candida* - *Aspergillus*
35
Echinocandins are currently licensed for use in what 2 situations?
- **Disseminated** and **mucocutaneous** candidal infections - **Emperic** antifungal therapy **during febril neutropenia** (replaced Amphotericin B)
36
What is the mechanism to resistance of Echinocandins?
**Point** **mutations** in **glucan synthase**
37
How are Echinocandins administered?
**Only IV** formulation
38
For which organism and specific situation is the use of the Echinocandin, Caspofungin indicated?
- Invasive aspergillosis - **Only** as **salvage therapy** in pt's that don't respond to amphotericin B
39
The Echinocandin, Micafungin, has a specific spectrum of activity against which organisms and in which situation is it indicated?
- Mucocutaneous candidiasis - Candidemia - **Prophylaxis** of candidal infections in **bone marrow transplant pt's**
40
Which anti-fungal is given for esophageal candidiasis and invasive candidiasis, includig candidemia?
Anidulafungin
41
Which Echinocandins has the longest half-life of 24-48 hours?
Anidulafungin
42
What is the black box warning for Flucytosine?
contraindicated or to be used with extreme caution in pts with: renal impairment pregnant/breast feeding bone marrow depression
43
The current use of glucytosine is in combination with what? For what condition?
Liposomal amphotericin B Cryptococcal meningitis
44
What is the black box warning for Micafungin?
hepatocellular tumors
45
Voriconizole has greatest affinity for which CYP?
CYP2C19
46
What is the black box warning for itraconazole? Waht is a common adverse effect associated with liver disease?
heart failure due to inotropic effects can cause severe liver disease with intractable vomiting
47
What can be seen on EKG in patients who take Fluconazole (especially when taken with drugs metabolized by CYP3A4) ?
QT prolongation leading to Torsades
48
What is the black box warning for Amphotericin B? Can lead to toxicity where?
used for treating life threatening fungal infections only Nephrotoxicity because it has an affinity for cholesterol on human cels
49
An overdose of amphotericin B can cause what cardiac issue?
Cardiac arrest

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