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med school things > Anti-Fungals > Flashcards

Anti-Fungals Flashcards

1
Q

What are the “yeast” species we have to worry about treating?

A

1) Candida species - C. albicans is most common, C. glabrata, and C. krusei
2) Cryptococcus neoformans

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2
Q

What are the endemic mycoses and what are the names of the disease states that they cause?

A

1) Histoplasma capsulatum - histoplasmosis
2) Blastomyces dermatitidis - blastomycosis
3) Coccidiodes immitis - coccidiomycosis
4) Sporothrix schenckii - sporotrichosis (not really an endemic)

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3
Q

What are the invasive molds we have to treat? Describe their hyphae

A

1) Aspergillus - most common, parallel wall 45° septated hyphae. Species include A fumigatus, A flavus, etc.
2) Aspergillus-like: look similar to Aspergillus. Includes Pseudallescheria boydii, Fusarium, Penicillium, etc. (45°, parallel wall).
3) Mucor (aka Zygomyces): Mucor and Rhizopus species (non-septated, non-parallel, 90° hyphae), causes mucormycosis

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4
Q

What are the non-invasive molds we have to worry about treating?

A

Dermatophytes:

  • Trichophyton
  • Microsporum
  • Tinea infections (including onychomycosis)
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5
Q

What are the mechanism of action and pharmacology (distribution, metabolism, excretion, half-life, dosing) of Amphotericin B?

A

MOA: Lipophilic molecule that binds ergosterol (but NOT cholesterol), increasing permeability and creating pores in the membrane, causing leakage of molecules including potassium.
Distribution: Doesn’t enter CNS but can treat fungal meningitis
Metabolism: Not hepatic
Excretion: Not renal**
Half-life: 24 hours with 15 day beta-phase half-life.
Dosing: Do NOT adjust dosing for renal function since it is not renally excreted. Except for Cryptococcus, don’t know how much to give. Lipid formulations are dosed 5-10x higher than conventional.
One of the strangest drugs we use

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6
Q

What is the spectrum of use of Amphotericin B? What doesn’t it cover well?

A

Fungicidal against most yeasts and molds.

  • Gold standard for most serious fungal infections.
  • Drug of choice for Candida endocarditis, endopthalmitis, meningitis
  • Initial therapy for cryptococcal, histoplasma, and blastomyces meningitis
  • Standard therapy for mucomycosis
  • Empiric treatment for persistent fever in neutropenic patients.

Does NOT cover: Pseudallescheria boydii, some other fungi.

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7
Q

What is the gold standard drug against which new anti-fungals are compared?

A

Amphotericin B

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8
Q

What is the main benefit and main drawback to lipid formulations of Amphotericin B compared to Conventional Amphotericin B?

A

Advantage: Significantly reduces renal toxicity, causing fewer acute reactions.

Drawback - costs $300-$1200 per day compared to $10/day

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9
Q

What toxicities are associated with Amphotericin B?

A
  • Acute and Infusion-related: Fever and rigors
  • Renal: Raises creatinine to 2-3 mg/dL
  • Metabolic: Causes hypokalemia, hypomagnesemia, and acidosis due to renal wasting of K+, Mg++, HCO3-
  • Hematologic: Everyone gets anemic

*Called amphoterrible

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10
Q

Which two types of drugs act at the fungal cell membrane?

A

1) Amphotericin B

2) Azoles

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11
Q

What is the mechanism of action and toxicity for Flucytosine?

A

MOA: Oral agent that interferes with nucleic acid synthesis.

-Bone marrow toxicity - levels must be carefully monitored but levels can’t be monitored in house.

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12
Q

How is flucytosine used to treat clinically? When is it used as a monotherapy?

A
  • Used in combination with amphotericin for first two weeks treatment for cryptococcal meningitis before switching to fluconazole.
  • Never. Even though it is active against Candida and Cryptococcus, resistance develops quickly when used alone.
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13
Q

What is the mechanism of action for the Azole class? Is it fungicidal or fungistatic?

A

MOA: Interferes with cell membrane by inhibiting ergosterol synthesis. Fungistatic for Candida.

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14
Q

What is the main problem with azoles in terms of toxicity?

A

They interfere with P450 enzymes, affecting metabolism of other drugs.

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15
Q

What is the mechanism, route, distribution, excretion, and toxicities associated with fluconazole?

A

MOA: Azole - inhibits ergosterol synthesis
Route: IV or Oral (oral less expensive) - once per day, easy to use.
Distribution: Great penetration to CSF, eye, urine.
Excretion: Renal - may need to adjust dose
Toxicity: Uncommon

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16
Q

What are the spectrum and clinical uses for Fluconazole?

A

Spectrum: Covers most yeasts, particularly Candida and Cryptococcus, but does not cover molds. Candida krusei is always resistant and Candida glabrata may be.

1) Drug of choice for Candida esophagitis
2) Candidemia: Equivalent to Ampho B. Should not be used if septic or due to resistant Candida (e.g. if we know their strain or if they recently used an azole)
3) Cryptococcosis: After 2 weeks, replaces Ampho B + Flucytosine combo therapy.
4) Antifungal prophylaxis in neutropenic patients.

17
Q

What are the route, distribution, unique use, and other uses of Itraconazole?

A

Route: Oral or IV
Distribution: Poor CSF penetration
Unique use: First azole that treats Aspergillus
Other uses:
- Drug of choice for sporothricosis
- Non-life threatning manifestations of endemic mycoses
- Pulse therapy for onychomycosis

18
Q

Describe the route, distribution, pharmacokinetics, and major side effect of Voriconazole

A

Route: PO or IV
Distribution: Great CSF penetration, poor urine penetration
Pharmacokinetics: Does dependent (increasing dose 200 -> 300 mg may increase serum levels by 2-3x - enzyme saturation)
Toxicity: Transient, mild visual disturbances (blurred, altered perception of colors/images, or photophobia)

19
Q

What are the clinical uses for Voriconazole?

A
  • Drug of choice for Aspergillus treatment (replaced itraconazole)
  • Used for Pseudallescheria boydii, which is always amphotericin resistant.
20
Q

What is Posaconazole? What are its route and uses?

A

It is the newest azole, and first that can treat Mucor species (although Ampho B is still drug of choice)

Route: PO
Uses:
1) 2nd line for mucormycosis
2) Antifungal prophylaxis in neutropenic patients

21
Q

What is the mechanism of action of Echinocandin drugs? What do they cover? How are they administered and dosed?

A

MOA: Inhibits synthesis of 1,3-ß-D glucan, preventing cell wall formation.
Uses: Fungicidal for Candida. ONLY covers Candida and Aspergillus
Dosing: IV, once daily, no adjustment for renal function

22
Q

What is the class, route, MOA, distribution, metabolism, and toxicity of Caspofungin? Does it require dose-adjustment?

A

MOA: Echinocandin - inhibits cell wall (1,3,ß-D-glucan) synthesis
Route: IV
Distribution: Poor CSF and urine penetration
Metabolism: Hepatic - adjust dose for liver disease
Toxicities: None

23
Q

What are the uses for Capsofungin

A

1) Candida esophagitis and Candidemia
2) Salvage therapy for Aspergillus
3) Empiric treatment of persistent fever in neutropenic patients

24
Q

What are the new Echinocandins and what are they approved for?

A

Micafungin, Anidulafungin

Only approved for Candida

25
Q

What is the first line appropriate treatment for Aspergillosis

A

Voriconazole

26
Q

What is the first line appropriate treatment for Blastomycosis

A

Mild - Itraconazole

Moderate to Severe - Amphotericin B

27
Q

What is the first line appropriate treatment for Coccidoidomycosis?

A

Mild - None
Moderate or Meningitis - Fluconazole
Severe - Ampho B

28
Q

What is the first line appropriate treatment for Cryptococosis?

A

First 2 Weeks: Amphotericin B + Flucytosine

Beyond 2 weeks: Fluconazole

29
Q

What is the first line appropriate treatment for Candidiasis?

A

Mild to Moderate: Capsofungin or fluconazole

Endocarditis or meningitis: Amphotericin B

30
Q

What is the first line appropriate treatment for Histoplasmosis?

A

Mild - none
Moderate - Itraconazole
Severe - Amphotericin B

31
Q

What is the first line appropriate treatment for Sporotrichosis?

A

Mild to Moderate - Itraconazole

Severe - Amphotericin B

32
Q

What is the first line appropriate treatment for Neutropenic fever?

A

Voriconazole OR Capsofungin OR Amphotericin B

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