Polyenes

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• Bind to ergosterol in the fungal cell membrane → formation of pores in the fungal membrane → disruption of electrolyte balance → cell lysis → cell death
  • It binds cholesterol to a degree, which explains a large number of its adverse effects.

Amphotericin B

Adverse effects

• Nephrotoxicity: Lipid-based formulations of the drug and IV hydration reduce nephrotoxicity.
• IV phlebitis
• Impaired renal tubule permeability → hypokalemia and hypomagnesemia (restoring K⁺ and Mg2+ while administering the drug can counter this effect)
• Fever, chills (amphotericin B is sometimes referred to as “shake and bake”)
• Bone marrow suppression, anemia
• Arrhythmias

Nystatin

• Routes of administration (too toxic for intravenous use)
  • Topical
    • Vaginal candidiasis
    • Diaper rash
  • Oral (swish and swallow): oropharyngeal candidiasis

Azoles

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• Mechanism of action
  • Inhibition of 14-alpha demethylase, a fungal cytochrome P450 → ↓ fungal synthesis of ergosterol from lanosterol → ↓ levels of ergosterol → membrane instability → cellular death.

Echinocandins

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• Drugs
  • Caspofungin
  • Anidulafungin
  • Micafungin
• Route of administration: IV
  • Mechanism of action: inhibition of β-glucan synthesis → disruption of fungal cell wall synthesis → ↓ resistance against osmotic forces → cell death
• Clinical use
  • Invasive aspergillosis
  • Invasive candidiasis (particularly biofilm-embedded Candida )
• Adverse effects
  • Flushing (due to release of histamine)
  • Hepatotoxicity
  • Gastrointestinal upset

Benzofurans (griseofulvin)

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• Route of administration: oral
• Mechanism of action: griseofulvin binds to keratin precursor cells → accumulation in keratin-rich tissues (e.g., nails, hair) → entry into the fungal cell → interference with microtubule function → disruption of fungal mitosis
• Clinical use: dermatophyte infections (e.g., tinea pedis)

Antimetabolites (flucytosine)

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• Route of administration: oral
• Mechanism of action: converted to 5-fluorouracil by fungal cytosine deaminase, thereby inhibiting DNA and RNA synthesis