Antifungals Flashcards
What is the action of Amphotericin B?
binds ergosterol to form pores in membrane that leaks potassium
What fungi is Amphotericin B active against?
- Candida albicans 2. Histoplasma 3. Cryptococcus 4. Coccidioides 5. Blastomyces
What are the adverse effects of Amphotericin B
Acute Kidney Injury (accumulates in PCT affecting absorption of Na, Cl), hypotension, anemia. Does not cross BBB or placenta
How is Amphotericin B administered?
Slow IV infusion, given with sodium flush before and after to avoid kidney toxicity
What is the action of Flucytosine
Converted to 5-flurodeoxyuridine monophosphate in fungal cells, inhibits DNA synthesis by inhibiting thymidylate synthase and RNA synthesis by inhibiting F-deoxyUTP.
What are adverse effects of Flucytosine?
Falling neutrophils
Liver dysfunction
Upchuck
Clotting
How is Flucytosine used?
Combined with other agents, systemic fungal infections -> broad spectrum agent, can cross BBB
What are the 4 azoles?
ketoconazole, fluconazole, voriconazole, posaconazole - AZOLES are assholes! lots of side effects and all teratogenic
What azole is used for aspergillus?
voriconazole
Which azole has the fewest side effects?
fluconazole
What is the mechanism of the azoles?
inhibit C14-alpha-demethylase, which blocks conversion of lanosterol to ergosterol (membrane structure)
What are side effects of Fluconazole?
teratogenic, GI effects and skin rash
What are side effects of ketonazole?
sex related, hepatotoxicity
What are side effects of Voriconazole?
frequent drug interactions (p450), visual and auditory hallucinations
What are side effects of posaconazole?
Liver dysfunction, give with high fat meal
How is resistance to azoles conferred?
mutation in C14-alpha-demethylase gene so drug can no longer bind to it
What are the echinocandins?
caspofungin, anidulafungin
What is the mechanism of the echinocandins?
inhibit Beta(1,3)-D-glucan (inhibits cell wall synthesis) which leads to cell lysis
What are capsofungin and anidulafungin useful against?
A for aspergillis and C for candida
What are adverse effects of echinocandins?
The F’s: fever, flebitis, flushing, and Rash
What is the mechanism of Griseofluvin?
accumulates in keritin-containing tissues, disrupts mitotic spindle and fungal mitosis
What are the uses of Grisofluvin?
ringworm, dermatophytosis of skin and hair. Give with Grease
What are adverse effects of Griseofluvin?
induces P450 drugs, increases metabolism of many drugs
How is Griseofluvin administered?
With “grise” – grease. Take with high fat meal
What is the mechanism of Terbinafine?
inhibits squalene epoxidase, which block synthesis of ergosterol in cell membrane. “Fungicidal”
What are the clinical uses of Terbinafine?
dermatophytoses, onchyomycoses (nails)
What are the adverse effects of Terbinafine?
The T’s. Taste, Toilet, transaminases (+ visual)
What is Nystatin used for?
topical treatment of candida or oral treatment with swishing and spit (minimal oral absorption)
What is the mechanism of nystatin?
forms pores in membranes allowing potassium efflux
What is the mechanism of Cilopirox?
inhibits transport, leads to decrease in DNA, RNA, and protein synthesis
What is Cilopirox used to treat?
Topical use: seborrheic dermatitis (1% solution), tina pedis, tinea corporis, onchyomycoses (8% solution)
