Antifungal drugs Flashcards
What are anti fungal drugs used for?
Used to treat/prevent fungal disease
What are fungal diseases known as?
Mycoses - Superficial: nail, scalp, mucous membranes. Systemic: affect internal organs - fatal.
What are fungal pathogens?
Eukaryotes an opportunistic pathogens.
What are the most common opportunistic fungal pathogens?
Candida albicans, aspergilus fumigatus, cryptococcus neofromans.
What puts patients at higher risk of developing fungal infections?
Impaired immune system - HIV/AIDS, organ transplantation, long-term abx, cancer. Menstrual cycle in women - 70% experience one episode of vaginitis caused by C.albicans.
What are the targets for anti fungal drugs?
Cell wall, plasma membrane, nucleus - DNA and RNA synthesis.
What does the fungal cell wall consist of?
Skeletal components - Glucan and Chitin.
Matrix components.
B1,3-Glucan - anti fungal targets.
What drugs inhibit the enzyme and synthesis of B1,3-Glucan?
Echinocandins: Caspofungin and Micafungin.
What is the difference between fungal plasma membranes and human plasma membranes?
Fungal cells contain ergosterol whereas human cells contain cholesterol. Fungal cells cannot grow and survive without ergosterol.
What is the action of antifungals that target ergosterol?
Either bind to resident ergosterol in the PM or inhibit different ergosterol biosynthetic enzymes and block synthesis of ergosterol.
What are the drugs called that bind to resident ergosterol?
Polyene Antifungals
How to Polyene Antifungals work?
Bind to ergosterol and form pores in the PM. The pores disrupt the membrane integrity causing leakage of cell contents.
What are the names of some polyene antifungals?
Amphotericin B.
Nystatin - used in oral and GI fungal infections.
What are the side effects of polyene antifungals?
Prolonged use has severe side effects such as kidney failure.
What are the drugs called that inhibit ergosterol biosynthesis?
Azoles.
How do Azoles work?
Inhibit the enzyme Lanosterol C-14 demethylase. This blocks ergosterol synthesis and leads to accumulation of toxic intermediates.
What are the two types of azoles?
Imidazoles and Triazoles.
Examples of Imidazoles?
Miconazole, Clotrimazole, Ketconazole.
Examples of triazoles?
Fluconazole, Voriconazole, Itraconazole.
What do Allylamines do?
Inhibit squalene to prevent the synthesis of ergosterol.
Examples of Allylamines?
Terbinafine, Amorolfine.
What drug targets RNA and DNA synthesis?
Flucytosine.
What is resistance to antifungals caused by?
Decreased accumulation of the drug, inactivation of the drug, mutations in drug target-encoding genes.
