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13 Cards in this Set
- Front
- Back
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Fungal Organisms |
-eukaryotic = difficult target -yeasts -molds |
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Dermatophyte |
parasitic fungus of the skin that can obtain nutrients from keratinized tissue **ringworm (tinea) ** nail infections (onychomycosis) -KOH prep confirmation test to avoid inappropriate glucocorticoid TX |
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Candidiasis |
yeast infections (oral or vaginal) |
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Risk Factors for Infections |
1.) surgical and intensive care 2.) prosthetics 3.) Immunosuppressed **4th most common nosocomial infection -systemic -superficial (subcutaneous or cutaneous) |
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Ergosterol Biosynthesis |
**maintains cell membrane structure/function 1.) squalene > (squalene epoxidase) > lanosterol 2.) lanosterol > (CYP450 14alpha-sterol demethylase) > ergosterol |
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Cell Wall |
Contains: 1.) chitin 2.) beta-D-glucans 3.) glycoproteins |
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Antifungal agent classes |
1.) inhibitors of fungal membrane stability 2.)Nucleic Acid Synthesis Inhibitors 3.) Mitosis Inhibitors 4.) Squalene Epoxidase Inhibitors 5.) 14alpha-sterol demethylase inhibitors 6.) Inhibitors of cell wall synthesis |
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Inhibitors of fungal membrane stability |
Prototype: amphotericin B & Nystatin Amphotericin B: poor oral absorption **given IV in deoxycholate colloidal suspension MOA: binds to ergosterol and disrupts membrane stability -forms pores, allows leakage, depolarization **fungistatic or fungicidal Therapeutic uses: broad spectrum -only for life-threatening systemic mycoses -start therapy then switch to azalea **nystatin: candidiasis Adverse: -cytokine storm (minimized by slow infusion) -renal toxicity (IV) -hematologic toxicity (myelosuppression) |
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Nucleic Acid Synthesis Inhibitors |
Prototype: flucytosine MOA: DNA and RNA synthesis inhibitor -5-FdUMP: inhibits thymidylate synthase **fungistatic **resistance in mono therapy: often used with ampho B Therapeutic Uses: -cryptococcal meningitis -systemic candidiasis Adverse: -Hematologic (bone marrow suppression) -Hepatoxicity -black box warning for renal insufficiency |
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Mitosis Inhibitors |
Prototype: griseofulvin MOA: binds tubulin and disrupts assembly of mitotic spindle **fungistatic **not active against candida or systemic mycoses ***long TX time!! Therapeutic uses: -dermatophytic infections Adverse: -HA -photosensitivity |
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Squalene Epoxidase Inhibitors |
Prototype: terbinafine MOA: lowers cell stability, squalene accumulation is cytotoxic **fungicidal Therapeutic uses: -ringworm (topical) -Onychomycosis (oral) Adverse: -DDI- inhibits CYP 2D6 and induces 3A4 -skin rxns, dysgeusia |
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14alpha-sterol demethylase inhibitors |
**AZOLES** 1.)triazole prototype: fluconazole 2.) imidazole prototype: ketoconazole MOA: inhibit fungal CYP P450 -no ergosterol= destabilized cell membrane **triazoles more selective for fungal CYP **agents have important differences= check susceptibility, oral bioavailability, special instructions, and ensure adequate absorption Therapeutic uses: -systemic mycoses -superficial mycoses Adverse: -GI upset -numerous DDI -avoid during pregnancy |
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Inhibitors of Cell Wall Synthesis |
**echinocandins Prototype: caspofungin MOA: inhibit beta-D-glucan synthesis -disrupts cell wall= osmotic stress and lysis **fungicidal Therapeutic uses: -IV for invasive aspergillosis -empiric tx for persistent febrile neutropenia -severe systemic candidiasis |
