Antifungal Agents Flashcards
1) What is the most common fungal infection associated with sepsis?
2) What fungal infection has the highest mortality rate?
3) Which fungal infection is an emerging threat?
1) Candida albicans
2) Aspergillus
3) Cadida auris
Amphotericin B
1) Mechanism of action
2) Use
1) Polyene Antibiotic: binds to ergosterol and forms pores in the membrane causing leakage of intracellular ions causing cell death
2) Drug of choice for treating most life-threatening systemic fungal infections
Nystatin
1) Mechanism of action
2) Use
1) Polyene Antibiotic: binds to ergosterol and forms pores in the membrane causing leakage of intracellular ions causing cell death
2) Drug of choice for candidate infections of the oral cavity
* *bitter taste!
1) What group of anti fungal drug is contraindicated when using amphotericin B? Why?
2) What other drugs are contraindicated with amphotericin B?
1) Azoles, because they inhibit ergosterol synthesis causing ergosterol concentrations in the membrane to decrease. This makes amphotericin ineffective.
2) nephrotoxic agents (ahminoglycosides, cyclosporine) and digitalis
What are the adverse effects of amphotericin B?
Immediate reactions: fever, chill, muscle spasm, vomiting, HA, hypotension
Slower reactions: nephrotoxicity
**IV has more serious reactions, slow infusion is better
Flucytosine
1) Mechanism of action
2) Use
1) 5-FU is metabolized to 5-FdUMP, which competitively inhibits thymidylate synthase. 5-FUTP is then incorporated by fungal cells into defective RNA
2) Orally effective for systemic fungal infections, **Used in combination with amphotericin B for synergistic effect
1) What is the basis for resistance to flucytosine?
2) What are the side effects of flucytosine?
1) mutations in cytosine permeate (channel into the cell) or cytosine deaminase (makes it metabolically active)
2) GI intolerance, **Bone marrow depression
Ketoconazole
1) Mechanism of action
2) Use
3) Adverse effect
1) Imidazole: inhibit ergosterol synthesis by blocking fungal CYP activity
* *Less specific for fungal CYPS than triazoles
2) Topical use
3) Inhibits adrenal and gonadal steroid hormone biosynthesis (endocrine side effects), drug interactions, hepatitis
Miconazole
1) Mechanism of action
2) Use
1) Imidazole: inhibit ergosterol synthesis by blocking fungal CYP activity
* *Less specific for fungal CYPS than triazoles
2) Topical: Oropharyngeal candidiasis, vaginal candidiasis, cutaneous candidiasis
Clotrimazole
1) Mechanism of action
2) Use
1) Imidazole: inhibit ergosterol synthesis by blocking fungal CYP activity
* *Less specific for fungal CYPS than triazoles
2) Oropharyngeal candidiasis in AIDs, oral-topical administration
* *more palatable alternative to nystatin
Fluconazole
1) Mechanism of action
2) Use
1) Triazole: inhibit ergosterol synthesis by blocking fungal CYP activity
2) Better CNS penetration so used for cryptococcal meningitis, systemic anti fungal for local and systemic infections, oropharyngeal candidiasis
* *NOT active against molds like Aspergillus
Itraconazole
1) Mechanism of action
2) Use
1) Triazole: inhibit ergosterol synthesis by blocking fungal CYP activity
2) Infections by Aspergillus and fluconazole-resistant candida (esophageal)
Terbinafine
1) Mechanism of action
2) Use
1) Allylamine: inhibits ergosterol synthesis by blocking the activity of squalene epoxidase
2) Dermatophytes, because it accumulates in the skin, nails, and fatty tissues. Mainstay for skin/nail infections
Caspofungin
1) Mechanism of action
2) Use
3) Spectrum of activity
1) Inhibit gluten synthesis which weakens the fungal cell wall, causing osmotic shock/lysis
2) Invasive candidiasis resistant to other antifungals, invasive aspergillosis/mold infections
3) aspergillus and candida
Micafungin
1) Mechanism of action
2) Use
1) Inhibit gluten synthesis which weakens the fungal cell wall, causing osmotic shock/lysis
2) Invasive candidiasis resistant to other antifungals, invasive aspergillosis/mold infections
3) aspergillus and candida
