Antifungal drugs Flashcards
What are the 5 classes of antifungal drugs?
Polyenes - amphotericin B
Azoles - Itraconazole
Pneumocandins - Caspofungin
Drugs used to treat dermatophytosis - Terbinafine
Fungi are ____
Eukaryotes
What are the main targets of antifungal drugs?
Cell wall - Pneumocandins
Plasma membranes - Polyenes and azoles
Protein synthesis and Nucleic acid synthesis
What do the plasma membranes of fungals contain?
ergosterol (the target of many antifungals)
Ergosterol instead of cholesterol.
What is the mechanism of action of Polyenes?
What is the problem with this?
Bind ergosterol in fungal membrane and forms a pore. This causes the fungal cell to lyse.
Polyenes will also bind cholesterol in host cells - toxic to host.
What is a polyene?
Amphotericin B (fungizone)
What are the pharmacokinetics of amphotericin?
Formulated with bile salts to improve solubility, however can cause adverse effects.
Poor oral absorption so given IV.
Distributes to ECF, poorly to CNS.
Most metabolized in the liver - bile, minority excreted in the urine.
Long half life (26 hours)
What is the spectrum of amphotericin?
Broad.
What are the uses of amphotericin?
Systemically - with life threatening systemic mycoses in dogs and cats.
Rarely in horses.
Absent in food animals.
Topical administration - in most species (SA, equine, exotics)
What are the adverse effects of amphotericin B?
The most toxic antimicrobial drug in clinical use.
Dose-dependant nephrotoxicity
IV administration should be SLOW
Lipid-complex formulations are much safer.
Azoles spectrum
Broad spectrum
What is the use of azoles?
Safe class of antifungal drugs - used for systemic antifungal therapy.
Topical use too.
Good oral bioavailability
What is the mechanism of action of azoles?
Works on the plasma membrane.
Inhibits fungal P450 enzymes involved in ergosterol formation.
Also stop host P450 enzymes - inhibits metabolism of concurrently administered drugs.
What are the azole antifungal categories?
Imidazole
Systemic - Ketoconazole
Topical - Clotrimazole and enilconazole and miconazole (too toxic for systemic use)
- Inhibit mammalian sterol synthesis (cortisol and testosterone), Endocrine adverse effects are common with systemic therapy.
Triazoles
Fluconazole
Itraconazole
Voriconazole
Less effect on mammalian sterol synthesis - very safe.
What are Ketoconazole used for?
Manage hyperadrenocorticism because of its ability to inhibit cortisol synthesis.
Spectrum Itraconazole
Oral absorption?
Steroid synthesis effect?
Fairly broad spectrum
Good oral absorption
No adverse effects on mammalian steroid synthesis
What is an Enchinocandins?
Caspofungin - inhibits cell wall synthesis.
Expensive
What is terbinafine?
Inhibits ergosterol synthesis in all dermatophytes.
