Flashcards in Antifungal Drugs Deck (22):
What is the mechanism of action of amphotericin B?
Binds to ergosterol in fungal cell membranes, forming "leaky pores".
What is the clinical use of amphotericin B?
Candidemia and infections caused by Aspergillus, Blastomyces, Cryptococcus, Histoplasma, Mucor, etc.
What are the pharmacokinetics of amphotericin B?
1. Multiple forms - IV for systemic infections (liposomal forms less nephrotoxic).
2. Topical for ocular/bladder infection.
What is the toxicity of amphotericin B?
1. Nephrotoxicity is dose-limiting, additive with other nephrotoxic drugs.
2. Infusion reactions (chills, fever, muscle spasms, hypotension).
Mention some important azoles.
What is the mechanism of action of azoles?
Inhibit fungal P450 dependent enzymes blocking ergosterol synthesis.
What are the clinical applications of azoles?
1. Aspergillosis (voriconazole)
2. Blastomycosis (itraconazole, fluconazole)
3. Mucormycosis (posaconazole)
4. Alternative drugs in candidemia and infections caused by Aspergillus, Blastomyces, Cryptococcus, and Histoplasma.
What are the pharmacokinetics of azoles?
1. Various topical and oral forms for dermatophytoses.
2. Oral and parenteral forms for mycoses (fluconazole, itraconazole, posaconazole, voriconazole).
3. Most undergo hepatic metabolism.
4. Fluconazole eliminated in urine unchanged.
What are the toxicities of azoles?
1. Ketoconazole is rarely used in systemic fungal infections due to its inhibition of hepatic and adrenal P450.
2. Other azoles are less toxic and may cause GI upsets and rash.
3. Voriconazole causes visual disturbances and is class D pregnancy risk.
Mention 3 main echinocandins.
What is the mechanism of action of echinocandins?
Inhibit β-glucagon synthase decreasing fungal cell wall synthesis.
What are the clinical applications of echinocandins?
Treatment of candidemia - caspofungin is also used as "salvage" therapy in aspergillosis.
What are the pharmacokinetics of echinocandins?
1. IV forms
2. Micafungin increases level of nifedipine and cyclosporine
What are the toxicities of echinocandins?
1. GI distress
2. Flushing from histamine release
What is the mechanism of action of flucytosine?
Inhibits DNA and RNA polymerase.
What are the clinical applications of flucytosine?
Synergistic with amphotericin B in candidemia and cryptococcal infections.
What are the pharmacokinetics of flucytosine?
1. Oral administration
2. Enters CSF
3. Renal elimination
What is a possible toxicity of flucytosine?
Bone marrow suppression.
What is the mechanism of action of terbinafine?
Inhibits epoxidation of squalene.
What are the clinical applications of terbinafine?
1. Mucocutaneous fungal infections.
2. Accumulates in keratin
What are the pharmacokinetics of terbinafine?
Oral administration - long duration of action (weeks).