Antifungal Drugs Flashcards
Most antifungals inhibit
Ergosterol
Rates of fungal infections in females
Lower pre puberty and post menopausal because ergosteorl looks like progesterone and estrogen
3 ways we attack fungi
Bind to ergosterol
Inhibit lanosterol demethylase
Inhibit Squalene epoxidase
Azole drugs mech, side effects, resistance
Drugs inhibit lanosterol demethylase (a p450 enzyme) (bind to heme)
Human and fungal have same enzyme…also a p450 enzyme and inhibit its expression…inhibit human sterol synthesis and drug metabolism
Mutations in lanosterol demethylase
Active site of P450 protein
Heme uses an iron to oxidize drugs and metabolites
What happens to P450 drugs with azoles
Increased concentrations
Fluconzaole use
Choice for candidiasis and both cryptococcal and coccidioidal meningitis
Dosage of fluconzaoler
Effective orally and also given IV…minimally metabolized and crosses BBB
Fluconazole side effcts
Fewer than ketoconazole…significant interactions (think statins, PIs, and cyclosporine)
Miconazole use
Topically and used for tinea corporis, tinea pedis, and vaginal candidosis
Side effects of miconazole
Side effects include local burning, itching, irritation
Jublia is more effective than
Terbinafine…jublia actually penetrates he toenail
Candida albicans tx
Azoles or polyenes
Histoplasma capsulatum tx
Azoles and polyenes especially itraconazole and amphotericin B
Blastomyces dermatidis tx
Itraconazole…amphotericin B is 2nd choice
Cryptococcus neoformans tx
Amphotericin B…if meningitis combine with fluconazole
Candida glabrata tx
Reistant to azoles and polyenes…treat with topical flucytosine and boric acid
Microsporum canis.audouni tx
infections of hair, nail, and toes…treat with griseofulvin
Amphotericin B mech
Disrupts cell membrane and binds ergosterol
Amphotericin B use and side effects
Broad spectrum
Fever and chills and allergic reactions (tx with tylenol)…principal, dose limiting toxicity is renal dysfunction…hypotension, hypokalemia, and others
Nystatin use, admin, and side effects
Similar to amphotericin but only topical tx for oral candidosis
Minimal absorption orally
Minial side effects topically
Flucytosine mechanism
Enters via cytosine-specific permease enzyme and converted to 5-FU by cytosine deaminase…eventually blocks DNA and protein synthesis by disrupting thymidylate sunthase
Mammalian cells do NOT convert flucytosine to fluorouracil
Resistance to flucytosine
Through decreased uptake of the drug by permease or decreased cytosine deaminase activity
Flucytosine admin and side effects
Well absorbed and penetrates orally…always used with amphotericin B to slow development of resistance
Leucopenia and thrombocytopenia…nausea, vomiting and diarrhea
Girseofulvin mech
Binds to MTs to disrupt the mitotic spindle and block replication in mitosis…specific to fungi
Griseofulvin administration
Orally…concentrates in skin at sites of newly synthesized keratin containing tissues…induces P450 enzymes
Griseofulvin side effects
Rare but could be allergic response, heachache, nausea, and liver toxocity
Terbinafine mech
Inhibits squalene epoxidase in ergosterol synthesis
Non-azole inhibitor of sterol synthesis
Terbinafine admin
Topically…administered orally, concentrates in skin and nail beds
Caspofungin mech
Inhibits 1,3-B-D-Glucan synthesis blocking cell wall synthesis
Good against candida and aspergillus…good for CNS as well…not absorbed in GI and must be injected
Limited side effects
