14.0 Antifungals Flashcards

1
Q

What is the MOA of Amphotericin B?

A
  • Binds to ergosterol, forming pores in cell membrane.

- Pores allow leakage of intracellular ions and macromolecules.

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2
Q

Describe the pharmacokinetics of Amphotericin B?

A
  • Amphotericin B is highly insoluble: formulated as deoxycholate colloidal suspension.
  • Poorly absorbed from the GI tract.
  • Must be given IV.
  • Penetration into the CSF is extremely low.
  • Intrathecal therapy may be necessary for meningeal disease.
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3
Q

What is important to know regarding the uses of Amphotericin B?

A

•Often used as initial induction regimen to rapidly reduce fungal burden.

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4
Q

Is Amphotericin B safe for pregnancy?

A

Yes

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5
Q

Describe the AE related with slower toxicity?

A
  • Amphotericin B also binds to cholesterol and forms pores in mammalian cell membranes, leading to renal toxicity.
  • Renal impairment occurs in nearly all patients.
  • Azotemia occurs in most patients.
  • GFR may be decreased.
  • Renal toxicity commonly presents with renal tubular acidosis with severe magnesium and potassium wasting.
  • Renal damage can be attenuated with sodium loading: it is common practice to administer saline infusion with amphotericin B.
  • Hypochromic normocytic anemia, due to reduced erythropoietin production.
  • Intrathecal administration can cause seizures and serious neurological damage.
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6
Q

What are the 3 FDA approved lipid formulations of Amphotericin B?

A
  • Liposomal amphotericin B (L-AMB)
  • Amphotericin B lipid complex (ABLC)
  • Amphotericin B colloidal dispersion (ABCD)
  • Nephrotoxicity is less common and less severe with the lipid formulations.
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7
Q

Flucytosine is what type of drug?

A

•Synthetic pyrimidine antimetabolite.

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8
Q

What enzyme takes up Flucytosine into fungal cells?

A

cytosine permease

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9
Q

Regarding MOA of Flucytosine, what is it converted to once it is taken up? What does this do?

A


Converted intracellularly first to 5-fluorouracil (5-FU) and then to 5-fluorodeoxyuridine monophosphate (5-FdUMP) which inhibits thymidylate synthetase, thus blocking synthesis of dTMP.

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10
Q

Combination of Flucytosine with what produces a synergistic effect?

A

•Combination of flucytosine and amphotericin B is synergistic.

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11
Q

What does 5-FUTP do?

A

•Fluorouridine triphosphate (5-FUTP) is also formed, which inhibits protein synthesis.

(Flucytosine MOA)

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12
Q

What is Flucytosine used for?

A
  • Indicated only for serious infections caused by susceptible strains of Candida and/or Cryptococcus.
  • Should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis in order to avoid resistance.
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13
Q

What are the AE of Flucytosine?

A
  • Result from metabolism (possibly by intestinal flora) to 5-fluorouracil.
  • Bone marrow toxicity is the most common.
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14
Q

What is the MOA of Azoles?

A
  • The fungal cytochrome P450 enzyme 14-α-sterol demethylase catalyzes the conversion of lanosterol to ergosterol.
  • Azoles inhibit the enzyme, thus reducing ergosterol synthesis.
  • This disrupts membrane function and increases permeability.
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15
Q

What is more specific than imidazoles?

A

Triazoles

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