Antifungals Flashcards
What are the two main types of fungal infections?
- Superficial Infections: Nails, skin, and scalp (e.g., Tinea pedis – athlete’s foot).
- Systemic Infections: Life-threatening, especially in immunocompromised patients (e.g., aspergillosis, candidiasis).
Name three key fungal pathogens and their characteristics.
- Candida albicans: Causes candidiasis; most common yeast infection.
- Aspergillus fumigatus: Produces airborne spores; affects weakened immune systems.
- Cryptococcus neoformans: Causes meningitis in immunosuppressed patients.
Why are fungal infections increasing in prevalence?
- Misuse of antibiotics disrupts the microbiome, encouraging fungal overgrowth.
- Rising immunosuppression due to HIV/AIDS and chemotherapy.
How do azoles inhibit fungal growth?
Inhibit ergosterol synthesis by blocking the fungal CYP450 enzyme responsible for converting lanosterol to ergosterol.
Name three examples of azoles and their uses.
- Ketoconazole: First azole for systemic infections; limited due to liver toxicity.
- Fluconazole: Drug of choice for fungal meningitis; used in HIV patients.
- Itraconazole: Effective for severe systemic infections.
How does terbinafine work?
- Inhibits fungal squalene epoxidase, disrupting ergosterol synthesis.
- Accumulation of toxic squalene leads to fungal cell death.
What is the primary use of terbinafine?
Topical: Treats superficial infections (e.g., Tinea pedis).\nOral: Treats nail infections (onychomycosis).
How do polyenes, such as amphotericin B, kill fungi?
- Bind irreversibly to ergosterol, forming membrane pores.
- Increase cell permeability, leading to cell death.
What are the uses and limitations of amphotericin B?
Use: Treat systemic infections like aspergillosis and cryptococcal meningitis.
Limitation: Causes nephrotoxicity, though liposomal formulations reduce toxicity.
How do echinocandins inhibit fungal growth?
Inhibit β-D-glucan synthase, disrupting fungal cell wall synthesis.
What are examples of echinocandins, and their use?
- Caspofungin, Micafungin, Anidulafungin.
- Used for invasive candidiasis in critically ill patients.
How does flucytosine target fungal cells?
- Enters fungal cells via cytosine permease.
- Converted to 5-fluorouracil (5-FU), inhibiting RNA and DNA synthesis.
Why is flucytosine often combined with amphotericin B?
Amphotericin B increases flucytosine uptake and reduces resistance development. Combination is effective for cryptococcal meningitis.
How does griseofulvin work against fungi?
- Inhibits fungal mitosis by binding tubulin, preventing microtubule assembly.
- Fungistatic: Inhibits growth but does not kill fungi.
What is Candida auris, and why is it significant?
- Emerging global health threat due to multidrug resistance.
- Often resistant to azoles, echinocandins, and amphotericin B.
Name three mechanisms of antifungal resistance.
- Altered Targets: Mutations in target enzymes (e.g., squalene epoxidase).
- Efflux Pumps: Actively pump drugs out of fungal cells.
- Reduced Uptake: Loss of cytosine permease reduces flucytosine uptake.
Which antifungal classes target ergosterol synthesis?
- Azoles: Block conversion of lanosterol to ergosterol.
- Terbinafine: Inhibits squalene epoxidase, leading to toxic squalene build-up.
What is the primary target of echinocandins?
β-D-glucan synthase, an enzyme required for fungal cell wall synthesis.
