Exam 8: Antifungal Agents Flashcards
What are 5 drugs used for systemic mycosis?
Amphoteracin B Ketoconazole Miconazole Fluconazole Itraconazole
When is empiric anti fungal therapy used? What are two drugs that are used?
In seriously ill, neutropenic patients.
Amphoteracin B or Miconazole
What are drugs used to treat Candidiasis?
Amphoteracin B
-Azoles
Nystatin
Terbinafine
What are 4 mechanisms of anti fungal drugs?
- Affect Membrane function (amphoteracin B)
- Affect Cell wall synthesis
- Affect Ergosterol synthesis
- Affect nuclear division (Griseofulvin)
describe the synthesis of Ergosterol
Squalene is converted to Lanosterol by Squalene monooxygenase
lanosterol is converted to ergosterol by c14 alpha demethylase (p450)
Amphoteracin B formulation challenge
It is insoluble, but i administered parenterally somehow
What is the mechanism of amphoteracin B?
Affects membrane function
Binds to ergosterol in the cell membrane, which causes pores to form and loss of membrane integrity.
What are 2 adverse effects of Amphoteracin B?
- Can also interact with human sterols, causing nephrotoxicity
- It can cause anemia by decreasing erythropoietin production
These are both due to affects of sterols in the kidney
What are two non fungal infections that are treated with amphoteracin?
Leishmaniasis Amebic meningoencephalitis (Naegleria fowler)
What are two types of -azoles? Which has a longer half life?
Imidazoles (2 nitrogens in the ring)
Triazoles (3 nitrogens in the ring)
Triazoles have a longer half-life
What are two triconazoles?
Itraconazole
Fluconazole
they have a longer half life (easier dosing)
What is the mechanism of -azoles?
Inhibition of 14 alpha demethylase that converts Lanosterol to Ergosterol
Disrupts the cell membrane
What are adverse effects of Ketoconazole?
Endocrine abnormalities (decreased androgen production) They shut down steroid synthesis they also inhibit p450 enzymes
How is fluconazole dosed?
once per day due to a pretty long half life
Griseofulvin mehcnaism
Disrupts mitotic spindle structure, arresting the cell in metaphase
how fast does griseofulvin work?
slowly, take weeks to months to work.
What is the mechanism of Nystatin?
Binds to sterols in the cell membrane (similar to amphoteracin B)
Disrupts cell membrane
How is nystatin used?
Topically, orally
Too toxic for parental use (as opposed to amphoteracin B)
Tolnaftate, Terbinafine mechanism
Inhibits squalene monooxygenase, inhibiting of Lanosterol…Ergosterol.
Caspofugin Mechanism
Inhibits B 1,3 glucansynthase (synthesis of glucans)
What is the use of Caspofugin?
Invasive cases of aspergillosis and esophageal candidiasis in patients who are refractory to other anti fungals
*** This is going to be on the test
What is the only specific use we have to know when it comes to anti fungals?
Caspofugin’s
