Anti-fungals Flashcards
What is considered the “gold standard” in antifungal therapy?
Amphotericin B Deoxycholate
What is the mechanism of action for Amphotericin B?
Binds to sterols (ergosterol) and alters the membrane permeability leading to leakage of essential cell contents and eventually cell lysis and death.
What is the major ADR for Amphotericin B?
Nephrotoxicity.
What is the mechanism of action of 5-fIuocytosine?
Penetrates fungal cell where it is deaminated by a fungal enzyme (cytosine deaminase). Competes with uracil inhibiting DNA, RNA and protein synthesis.
Does fIuocytosine distribute to CSF?
Yes, 60-100%
What are the Imidazoles?
- Ketoconazole (PO/Topical)
2. Miconazole (IV/Topical)
What are the Triazoles?
- Fluconazole (PO/IV)
- Itraconazole (PO)
- Voriconazole (PO/IV)
- Posaconazole (PO)
What is the mechanism of action for Azole anti-fungals?
Interfere with the fungal cytochrome P-450-dependent enzymes responsible for the demethylation of lanosterol and conversion to ergosterol.
What is the drug of choice for coccidioidomycosis?
Fluconazole.
What is the mechanism of action for caspofungin acetate?
Blocks fungal cell wall synthesis. Glucan synthesis inhibitor.
What is the spectrum of activity for Amphotericin B?
- Aspergillosis
- histoplasmosis
- Blastomycosis
- Coccidioidomycosis
- Paracoccidioidomycosis
- Cryptococcus
- Candida (topical only)
What is the benefit to Amphotericin B Lipid formulations?
- Lower incidence of nephrotoxicity
- Equal efficacy to parent compound
What ADRs occur with 5 Fluocytosine and when are they most common?
- Bone marrow hypoplasia
- More common in prolonged therapy or when in combination with Ampho B
What are the indications for 5-Fluocytosine?
- Serious infections of candida and cryptococcus
- Possible synergistic effect with Ampho B
- Cryptococcal meningitis (combo with Ampho B)
What are the ADRs for Azole antifungals?
- Nausea/vomiting
- Ketoconazole: dose dependent depression of serum testosterone and adrenocorticotropic hormon
- Hepatitis (rare)
- Most in first 3 months
- Increased aminotransferases
What are drugs do azole antifungals interact with?
- Antacids, PPIs and H2 antagonists
- Not seen with fluconazole or voriconazole
- Cyclosporin
- Warfarin
What is the drug interaction between azoles and antacids, PPIs and H2 antagonists?
Decreased absorption due to decreased acidic environment.
What are the drug interactions between azoles and cyclosporin?
Increased cyclosporin concentrations.
What are the drug interactions between azoles and warfarin?
Increased anticoagulation effect.
What is the spectrum of activity for Ketoconazle?
- Histoplasmosis
- Blastomycosis
- Coccidioidomycosis
- Candidiasis
- Tinea
- Vulvovaginal candidiasis
What is the bioavailability of Fluconazole taken orally?
F > 90%
How is Fluconazole eliminated?
- Renal excretion
- 60-80% unchanged in urine
What is the spectrum of activity for Fluconazole?
- Cryptococcal infections
- Coccidioidomycosis (drug of choice)
- Candidiasis
- Prophylaxis of candidiasis
How well does itraconazole distribute into the CSF?
Poorly.
