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Introduction
  • Drugs (all systemic unless otherwise noted)
    • amphotericin B
    • nystatin
      • topical formulation only
    • terbinafine
      • topical or systemic
    • echinocandins
      • anidulafungin
      • caspofungin
      • micafungin
    • azoles
      • topical formulations (too toxic for systemic use)
        • clotrimazole
        • miconazole
        • econazole
      • systemic
        • itraconazole
        • fluconazole
        • isavuconazole
        • ketoconazole (can also be topical)
        • voriconazole
    • griseofulvin
    • flucytosine
    • selenium sulfide
      • topical formulation only
  • Clinical use
    • fungal infections
 
Anti-Fungal Medications
Drug Mechanism of Action
Adverse Effects of Systemic Treatment
Indications
Amphotericin B
  • Binds to ergosterol in the membrane that is unique to fungi, forming membrane pores through which electrolytes and other cell content leak 
  • Can be fungistatic or fungicidal
  • Fevers, chills, and flu-like reaction
  • Renal toxicity
    • hydrate
    • supplement potassium and magnesium
  • Arrhythmias
  • Anemia
  • IV phlebitis
  • Systemic mycoses
    • Cryptococcus
    • Blastomyces
    • Coccidioides
    • Histoplasma
    • Candida
    • Mucor
Nystatin
  • Binds to ergosterol
  • Can be fungistatic or fungicidal
  • Topical formulation only
    • adverse effects are too toxic for systemic use
  • Oral candidiasis
  • Topical yeast infection
    • diaper rash
    • vaginal candidiasis
    • intertrigo
Terbinafine
  • Inhibits squalene epoxidase, an enzyme in fungi that is key in lanosterol synthesis
  • Fungicidal
  • Gastrointestinal upset
  • Liver toxicity (rarely, can cause fulminant liver failure requiring liver transplant)
  • Taste disturbance
  • Widespread dermatophyte infections
  • Onychomycosis
Echinocandins
  • Disrupts cell wall synthesis by inhibiting beta-glucan synthesis
  • Can be fungistatic or fungicidal
  • Gastrointestinal upset
  • Flushing
    • mediated by histamine
  • Aspergillosis
  • Candida
Azoles
  • Inhibits 14-alpha-demethylase, which is key in ergosterol synthesis in fungi
  • Fungistatic
  • Anti-androgen effects via inhibiting testosterone synthesis
    • gynecomastia (in particular, ketoconazole)
  • Inhibits cytochrome P450
  • Local mycoses
  • Mild systemic mycoses
  • Specific indications
    • fluconazole
      • chronic suppression of Cryptococcus in immunosuppressed patients
    • itraconazole
      • Blastomyces
      • Coccidioides
      • Histoplasma
    • voriconazole
      • Aspergillus
      • Candida
    • isavuconazole
      • Aspergillus
      • Mucor
Griseofulvin
  • Disrupts mitosis via microtubule dysfunction
  • Especially targets keratin-containing tissues such as nails
  • Fungistatic
  • Teratogenic
  • Disulfiram-like reaction
  • Neurologic symptoms
    • confusion
    • headaches
  • Induces cytochrome P450
  • Superficial infections
  • Dermatophytes
    • inhibits growth
Flucytosine
  • Converted by fungal enzyme cytosine deaminase to 5-fluorouracil, which then inhibits nucleic acid synthesis
  • Can be fungistatic or fungicidal
  • Bone marrow suppression
  • Systemic mycoses
    • Cryptococcus
Selenium sulfide
  • Disrupts mitosis, resulting in decreased turnover of epidermal cells and decreased flaking
  • Also has mild antibacterial and antifungal activity
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  • Seborrheic dermatitis
  • Pityriasis versicolor
 

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Questions (1)

(M1.MC.15.75) A 57-year-old florist presents to his family physician with nodular lesions on his right hand and forearm. He explains that he got pricked by a rose thorn on his right "pointer finger" where the first lesions appeared, and the other lesions then began to appear in an ascending manner. The physician prescribed a medication and warned him of gynecomastia as a side effect if taken for long periods of time. Which of the following is the mechanism of action of the medication? Tested Concept

QID: 106869
1

Inhibits ergosterol synthesis

62%

(116/188)

2

Binds to ergosterol, forming destructive pores in cell membrane

17%

(32/188)

3

Inhibits squalene epoxidase

12%

(23/188)

4

Inhibits formation of beta glucan

3%

(5/188)

5

Disrupts microtubule function

5%

(10/188)

L 1 D

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