Antifungals Flashcards
What are the risk factors for acquiring fungal infections?
- broad spectrum antibiotics
- indwelling catheters
- immunocompromised
What is the most common fungal target for drug therapy?
Ergosterol
What is the only broad spectrum antifungal used for serious systemic infections?
Amphotericin B
What is the unique mechanism for Amphotericin B and how’s administered?
Very Lipophilic and binds ergosterol in the membrane of the fungi causing membrane leakage and death. IV dose only.
What type of toxicity does Amphotericin B have and what are the effects?
Total Cumulative Dose Toxicity.
Symptoms - Renal Damage, can cause potassium imbalance.
What antifungal is used with Amphotericin B for serious Candida and Cryptococcus infections?
Flucytosine
What is the unique enzyme that Candida and Cryptococcus express that Flucytosine takes advantage of?
Fungal Cytosine Deaminase
Converts Flucytosine to 5-FU, which inhibits fungal DNA replication
How does the synergy between Flucytosine and Amphotericin B work?
Administering Flucytosine with Amphotericin B allows the Amphotericin B dose to be lower with same effects, thus less side effects.
What are common side effects of Flucytosine? What patients should you not use it with?
Leukopenia and Thrombocytopenia
Heptatoxicty
–Should not use with renal insufficiency or bone marrow suppression patients–
What is the common mechanism of Triazoles and Imidizoles?
Inhibits 14-alpha-sterol demethylase preventing ergosterol synthesis, which is a fungal P450.
What antifungal would be used to treat cryptococcus meningitis?
Fluconazole
What triazoles would be used to treat urinary candida?
Fluconazole (Diflucan) - penetrates CNS and urinary tract tissues.
What antifungal would be used to treat Blastomyces, Histoplasma, and oral Candida?
Itraconazole
What azole would be used to treat invasive Aspergillus and common strains of Candida?
Voriconazole
What are the limitations of Itraconazole and Voriconazole?
They cannot penetrate CNS or urinary tract.
Only Fluconazole can be used for Candida UTIs and CNS infections. Secreted in urine unchanged.
What are general side effects of azoles?
Heptatoxicity
Many drug interactions
What azole inhibits CYP3A?
Itraconazole
Which azole can cause visual disturbances and photosensitive rash?
Voriconazole
What drug is used for invasive Aspergillus and difficult Candida?
Caspofungin
How does Caspofungin work?
Noncompetitively inhibits Beta-(1,3)-D-glucan preventing cell wall synthesis
When would you use Caspofungin?
Invasive Aspergillus and Candida
–or if patients on intolerant to other drugs, or reached their maximal dose. –
What antifungal is used to treat urinary tract and mucous membrane Candida?
Fluconazole
What is another antifungal that has the same mechanism as Fluconazole and can be used as suppositories?
Miconazole
What antifungals are typically used as topical application for Candida?
Clotrimazole and Nystatin
