Antifungal Drugs (Systemic Mycoses) Flashcards
Candidiasis, aspergillosis, cryptococosis, and mucormycosis are all ____ types of systemic mycoses infections
opportunistic - occur in IC patients
Name the non-opportunistic systemic mycoses infections
sporotrichosis, blasomycosis, histoplasmosis, and cocidiomycosis
What is the clinical use of Amphotericin B, Azoles, Echinocandins, and Fucytosine classes of drugs?
antifungal drugs
What are the adverse effects of Amphotericin B?
nephrotoxic - binds to cholesterol and other sterols in human membranes
What is the MOA for amphotericin B?
Amphotericin binds to ergosterol, facilitates pore formation
How is Amphotericin B administered?
IV; slowly
There are 3 liposomal formulations of amphotericin B that have higher therapeutic indexes than amphotericin B. Why is this?
liposomal formulations transfer amphotericin B to fungal membranes and less to human membranes
In regards to drug interactions, which drugs should amphotericin B not be used with?
other nephrotoxic drugs (ahminoglycosides, NSAIDS, cyclosporine)
Which drug should be given with amphotericin B?
Flucytosine - the dosage and toxicity of amphotericin B can be reduced with combination use
What are the two types of Azoles?
Imidazoles: clotrimazole, ketoconazole
Triazoles: itraconazole, fluconazole
How is Itraconazole (Triazole) administered?
orally - safer than amphotericin B
What are the adverse effects of Itraconazole (Triazole)?
liver toxicity, cardiosuppression
Why is ketocanzole (Imidazole) hardly ever used?
FDA limits due to potentially fatal liver injury and risk of adrenal gland problems
What is the MOA of the Azoles class of drugs?
inhibit ergosterol synthesis - bind to cyt P450
What are the adverse effects of the Azoles class of drugs?
toxicity depends on affinity for mammalian and fungal cyt P450
note: Triazoles tend to have fewer side effects, better absorption
Itraconazole (Tirazole) and Ketoconazole (Imidazole) inhibit ____ and could increase the levels of other drugs if co-administered
CYP3A4
What type of drugs decrease absorption of itraconazole (Triazole)?
drugs that raise gastric pH, H2 antagonists, and proton pump inhibitors
Fluconazole (Triazole) is associated with what syndrome?
Stevens-Johnson Syndrome
Flucytosine is used to treat Candida in combination with _____
amphotericin
What is the MOA of Flucytosine?
converted to 5-FU by FUNGAL cytosine deaminase - inhibits thymidylate synthetase - inhibits DNA synthesis
What are the two types of Echinocandins?
Caspofungin, Micafungin
What is the MOA of the Echinocandins?
Inhibit synthesis of beta-1,3-D-glucan (cell wall component)
What would be the drug of choice for an Aspergillosis infection caused by Aspergillus species?
Amphotericin B
What would be the drug of choice for a Blastomycosis infection caused by Blastomyces dermatitidis?
Amphotericin B or itraconazole
What would be the drug of choice for a Candidiasis infection by the Candida species?
Fluconazole or Caspofungin
What would be the drug of choice for Coccidioidomycosis infection caused by Coccidioides immitis?
Amphotericin B or fluconazole
What would be the drug of choice for a cryptococcosis infection caused by cryptococcus neofromans?
Amphotericin B +/- flucytosine
What would be the drug of choice for chronic suppression Histoplasmosis?
Fuconazole
What would be the drug of choice for a Sporotrichosis infection?
amphotericin B or itraconazole
