Anti-Fungals Flashcards
What cellular structure do Echinocandins target?
Cell wall: glucan synthesis
What cellular structure do Polyenes and Azoles target?
Cell membrane: ergosterol synthesis
What cellular structure do Flucytosines target?
DNA/RNA synthesis: pyrimidine analogues
What is the mechanism of action of polyenes?
Bind directly to ergosterol
What are the polyenes?
Amp-B
Nystatin
How would you treat cryptococcal meningitis?
- Amp-B w/ Flucytosine
2. Fluconazole
Which azole crosses the BBB?
Fluconazole
What is the mechanism of action of Allylamines?
Inhibit fungal squalene epoxidase –> cannot convert squalene to lanosterol
Interfere with ergosterol synthesis
What is ergosterol?
Sterol that is part of the fungal bilayered cell membrane
What are fungal cell walls comprised of?
90% chitin, GLUCAN, mannan
10% proteins, glycoproteins
What do anti-fungals target?
Proteins
Nucleus
Cell wall, especially glucan
Cell membrane, especially ergosterol
Effective anti-fungals typically have a _____, which leads to ______.
High therapeutic index / many adverse side effects
What was the first anti-fungal and when was it approved?
Nystatin – 1954
What class of anti-fungals is Terbinafine?
Allylamine (targets squalene epoxidase)
What is the mechanism of action of Azoles?
Bind to and inhibit cytochrome p450 and 14-alpha demethylase –> cannot convert lanosterol to ergosterol
What class of anti-fungals is Flucytosine?
Antimetabolite (pyrimidine analogue)
What are side effects of Amp-B?
Chronic: Dose-dependent severe nephrotoxicity (decrease in GFR); may require dialysis
Acute: chills, fever, vomiting
What OTC drug can you NOT take with azoles?
Antacids. Azoles are weak acids, therefore an antacid would inhibit them.
What are the imidazoles?
Ketoconazole
Miconazole
What are the triazoles?
Itraconazole
Fluconazole
**these drugs are newer and less toxic
Broad spectrum
PO administration
Mostly replaced by Fluconazole
Ketoconazole
Side effects of Ketoconazole
Gynecomastia
Hepatic failure
Topical and vaginal suppositories
Dermatophytes
Miconazole
Topical and vaginal suppositories
Clotrimazole
Oral, esophageal, and vaginal candidiasis
Used for Cryptococcal meningitis (after initial treatment with Amp-B and Flucytosine)
Oral and IV
Fluconazole
**only azole to cross BBB
Broad spectrum including tinea unguium
Indicated for systemic fungal infections
Also for oral and esophageal candidiasis
Itraconazole
Oral and IV introduced in 2002
High bioavailability
Indicated for invasive Aspergillosis
Voriconazole
How would you treat superficial fungal infections?
Terbinafine
What is Flucytosine used for?
Systemic Candida and Cryptococcus neoformans infections
What is Flucytosine not effective against?
Aspergillus
What is the mechanism of action of the Echinocandins?
Inhibit 1,3-beta-glucan synthase
Cell wall synthesis inhibitor
What class of anti-fungal is Caspofungin?
Echinocandin
What is Caspofungin used for?
Invasive Amp-B resistant Aspergillosis
Esophageal Candidiasis
Pneumocystis pneumonia
How would you treat Coccidioides immitis?
- Flucytosine
- Fluconazole, Ketoconazole, Itraconazole
- Amp-B
How would you treat Pneumocystis jiroveci?
TMP/SMX
How would you treat Mucor/Rhizopus?
Amphotericin B
**this infection has a 50% mortality rate even with early diagnosis
