Antifungals and antiprotozoals Flashcards
Azoles (ketokonazole, fluconazole, clotrimazole, itraconazole, voriconazole). Mechanism and usage
Inhibits the synthesis of fungal ergosterol from lanosterol by blocking the cyp450 enzyme (14 alpha demethylase). Used for local systemic mycoses (Histoplasmosis, blastomycosis, coccidiomycosis).
What is fluconazole used for?
Chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections of all types.
Azoles Toxicity
Blocks testosterone synthesis (gynecomastia, especially with ketoconazole).
Liver dysfunction (because inhibits cytochrome P450)
Amphotericin B Mechanism and Usage
Binds to ergosterol and forms a pore in the fungal membrane. This causes leakage of electrolytes. Used for serious systemic mycoses (Histo, blasto, coccidiomycosis,).
How to administer Amphotericin B
With K+ and Mg2+ because of altered renal tubule permeability.
Amphotericin B toxicity
This is a shitty drug (amphoterrible) Fever/chills (shake and bake), hypotension, nephrotoxicity, arrhytmias, anemia, IV phlebitis.
How to reduce amphotericin toxicity
Concurrent hydration to decrease nephrotoxicity.
Liposomal amphotericin is better.
Also make sure to give K and Mg due to altered renal tubule permeability.
Nystatin mechanism and usage
Binds to ergosterol and makes a hole in the membrane for electrolyte leakage. Used as a swish and swallow for oral candidiasis. Topicall for diaper rash or vaginal candidiasis.
Nystatin administration
Topical form because too toxic for systemic use
Flucytosine mechanism and useage
Used in the treatment of cryptococcus in combination with amphotericin B.
Inhibits DNA and RNA biosynthesis by conversion to 5FU by cytosine deaminase.
Flucytosine Toxicity
Bone marrow suppression
Echinocandins (caspofungin, micafungin, andiulafungin) mechanism and usage
Inhibits cell wall synthesis by inhibiting synthesis of B-glucan.
Used for invasive aspergillosis, candida
Echinocandins toxicity
GI upset, flushing (histamine release)
Terbinafine mechanism and usage
Used for onchomycosis (and dermatophytoses)
Inhibits squalene epoxidase, which prevents squalene epoxide, which prevents synthesis of lanoesterol and finally ergosterol.
Terbinafine toxicity
Gi upset, headaches, hepatotoxicity, taste disTURBANce.
