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Flashcards in Antifungals Deck (6)
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1
Q

Polyenes: Amphotericin B and Nystatin

A

MOA; Binds ergosterol, creating holes in membrane allowing leakage of electrolytes. Fungicidal.

Spectrum: Broad. Used for invasive systemic fungal infections in immunocompromised patients. Active against yeast and molds.

Distribution: Long half life and can cross blood brain barrier.

Adverse effects: Amphotericin B TOXIC because it can bind cholesterol. 80% have nephrotoxicity. Nystatin is mainly topical candida

Resistance: Rare, decreased ergosterol in membrane.

2
Q

Azoles- Fluconazole, Itraconazole, Ketoconazole, -azole

A

MOA; binds fungal p450 enzyme (erg11) blocking production of ergosterol and causing an accumulation of Ianosterol. Fungistatic

Spectrum: Most widely used antifungal; varies by agent

Distribution: Orally available though cola/acid helps facilitate absorbtion of itraconazole, ketoconazole

Toxicity: Drug-Drug interactions, hepatotoxicity, neurotoxicity, alters hormone synthesis. Pregnancy class D.

Resistance: Altered P450, Efflux transporters.

3
Q

Allylamines- Terbinafine (Lamisil)

A

Mechanism: Fungicidal, inhibits squalene epoxidase, which leads to toxic accumulation of squalene

Spectrum: Dermatophytes

Toxicity: Topical, drug interactions with CYP2D6 substrates

Resistance: Rare in human pathogens but could include decreased uptake, mutant binding site, and substrate efflux.

4
Q

Flucytosine (5-FC)

A

MOA: Antimetabolite selectively taken up and converted to 5-fluorouracil in fungi, interfering with DNA and RNA synthesis. Fungistatic.

Spectrum: Narrow - Yeast

Distribution: Oral, Penetrates CNS

Toxicity: Only partially selective for yeast. can lead to bone marrow suppression - follow patient’s cell counts closely.

Resistance: Loss of converting enzyme or transporters, rarely used monotherapy –> cotreat with amphotericin B to increase uptake and minimize the likelihood of developing resistance.

5
Q

Griseofulvin

A

MOA: Binds microtubules inhibits spindle leading to multinucleate cells, fungistatic.

Spectrum: Dermatophytes

Distribution: Lipids increase oral absorbtion and then concentrates in dead keratinized layer of skin

Toxicity: Teratogenic (Pregnancy Class D)

Resistance: change to beta-tubulin, need to take orally for months so if patient is not adherent resistant mutations are more likely to develop

6
Q

Echinocandins - Caspofungin

A

MOA: Cell wall inhibitor blocks synthesis of Beta (1-3)-d-glucan polysaccharide. Fungicidal (Candida) and Fungistatic (Aspergillus)

Spectrum: Candida albicans, systemic

Distribution: IV, large molecular weight prohibits CNS penetration

Toxicity: limited, fever, rash at site of injection

Resistance: change in (1,3)-beta-D-glucan synthase gene