Antifungal agents Flashcards
What is the MOA of capsofungin?
Inhibits the synthesis of beta glucan (component of the fungal cell wall)
What is the MOA of the “-azoles”?
Inhibit 14-alpha-demethylase (enzyme used to convert lanosterol ergosterol(cell membrane component))
What is the MOA of terbinafine?
Inhibits squalene epoxidase (converts squalene to squalene epoxide)
What is the MOA of amphotericin B?
Binds to ergosterol (a component of the fungal cell membrane) to form artificial pores which disrupt membrane permeability
Name examples of polyenes
- Amphotericin B
- Nystatin
What is the mechanism of resistance to amphotericin B?
Low ergosterol content
What are the clinical uses of the polyenes?
- Amphotericin B has wide spectrum-DOC (or co-DOC) for severe infx caused by cryptococcus or mucor
- Nystatin-too toxic for systemic use-used topically for localized infx (candidiasis)
What other antifungal is synergistic with amphotericin B and what is this combo used to treat?
Amphotericin B is synergistic with flucytosine in cryptococcoses
What are the possible side effects of amphotericin B?
- Infusion related-fever, chills, muscle rigor, hypotension, occur during IV infusion
- Dose-dependent-nephrotoxicity, tubular acidosis
What is ketoconazole used for?
- Co-DOC for paracoccidioides and backup for blastomycoses and histoplasma
- Oral use in mucocutaneous candidiasis or dermatophytoses
What is fluconazole used for?
- DOC for esophageal and invasive candidiasis and coccidioidomycoses
- Prophylaxis and suppression in cryptococcal meningitis
What are itraconazole and voriconazole used for?
- DOC in blastomycoses and sporotrichoses
- Backup for several other mycoses and candidiasis
What is voriconazole used for specifically?
Aspergillosis
What are clotrimazole and and miconazole used for?
Used topically for candida and dermatophyte infx
What is the only “-azole” that penetrates the CSF (can be used for meningeal infx)?
Fluconazole
How is fluconazole eliminated from the body?
Eliminated in the urine (largely unchanged)
How are ketoconazole and itraconazole eliminated from the body?
Metabolized by liver enzymes
Which “-azole” is a p450 inhibitor?
Ketoconazole
What are the possible side effects of the “-azoles”?
- Decreased synthesis of steroids, including cortisol and testosterone -> decreased libido, gynecomastia, and menstrual abnormalities
- Increased LFTs and hepatotoxicity
What is the MOA of flucytosine?
Flucytosine is activated by fungal cytosine deaminase to 5-FU which is incorporated in fungal RNA
-5-FU also forms 5-FdUMP which inhibits thymidylate synthase -> decreased thymine
What happens if flucytosine is used alone?
Resistance develops quickly
What is flucytosine used for?
Use in combination with amphotericin B in severe candidal and cryptococcal infx-enters CSF
What is the main side effect of flucytosine?
Bone marrow suppression
What is the MOA of terbinafine?
Inhibits squalene epoxidase -> decreased ergosterol
What is terbinafine used for?
Dermatophytes and onychomycoses
What are the possible side effects of terbinafine?
GI distress, rash, headache, inc LFTs
What are examples of echinocandins?
Capsofungin and other “-fungins”
What is the MOA of the echinocandins?
Inhibit the synthesis of beta-1,2 glucan (critical component of fungal cell walls)
What are the echinocandins used for?
Backup drugs given IV for disseminated and mucocutaneous candida infx or invasive aspergillosis
What is the mechanism of resistance to “-azoles”?
Decreased intracellular accumulation
