Anti-Fungals Related to the Respiratory System Flashcards
What drug is specifically formulated for Aspergillus infections?
Voriconazole
What is the MOA of all “azoles”?
Azoles inhibit the CYP conversion of lanosterol to ergosterol, a necessary component for the fungal cell wall.
What is a common trait/side effect of all azoles that you need to watch for when a patient is on other medications?
All azoles are CYP inhibitors. (competitive) They decrease the clearance of other drugs.
Your patient has a cutaneous infection on his face. Tissue sample reveals non-septate hyphae branching at 90 degrees. What does he have and how do you treat it?
Mucor and Rhizopus. Surgical excision of necrotic tissue, followed by Ambisome. Another option is Posaconazole, an IV azole.
What’s the weird trait of Pneumocystis jiroveci that renders it unresponsive to normal anti-fungal agents?
Pneumocystis has cholesterol on its cell membranes rather than ergosterol, so it responds to anti-bacterials rather than anti-fungals.
What drug do you give a patient with pneumocystis jiroveci?
Trimethoprim/Sulfamethoxazole
In what typical patient does an infection with pneumocystis occur? At what point do you give them TMP/SMX prophalactically?
An AIDS patient with a CD4+ count of <200. Anything above that they can fight off. Give prophylactic Trimethoprim/Sulfamethoxazole when their CD4+ count is less than 200.
Your patient is a spelunker, by trade, and comes in complaining of fever, chills, chest pain, and night sweats. He is a resident of Mississippi. Sputum culture reveals tuberculate macroconidia. Staining with methenamine silver shows little dots inside what appear to be macropahges. What does your patient have and what do you treat it with?
Histoplasmosis. Treat the pulmonary infection with oral Itraconazole. If disease is severe, treat with IV Ambisome (Amphotericin B).
You’re a doctor in Arizona. It’s the week after an earthquake and people are piling in your clinic with flu-like symptoms. A pregnant woman and a Fillipino immigrant, however, have the flu symptoms with superimposed skin lesions and erythema nodosum. Blood test reveals peripheral eosinophilia. Microscopic examination of the sputum reveals speheres that look like gumballs filled with sprinkles (to put it scientifically). What is bothering your patients? How do you treat the people with flu-like symptoms? The Immunocompromised patients?
Coccidioides immitis. “Valley fever.” Mild, Flu like -> Oral ketoconazole, itraconazole, or fluconazole. Disseminated disease –> IV Ambisome, followed by one of the above drugs orally.
what is this? How do you treat it?
Blastomyces dermatidis. See the broad based bud and the double refractive membrane?
Itrazconazole.
Ambisome IV if disseminated.
What is this?
What does it cause in Immunocompetent people?
What does it cause in Immunocompromised people?
How do you treat it in each case?
Cryptococcus neoformans
Causes pneumonia in the immunocompetent, mostly asymptomatic. Treat with Oral Fluconazole (Crosses BBB)
Causes pneumonitis and cryptococcal meningitis in the immunocompromied. Treat with IV Ambisome and flucytosine.
MOA of flucytosine.
Only Antifungal that has aciton in the nucleus.
Inhibits thymidylate synthase, therefore prevents synthesis of pyrimidines and nucleic acid synthesis.
Worst side effect of flucytosine.
Blood dyscrasias and anemia.
Hair loss.
MOA of Amphotericin B (and Ambisome)
Blocks the incorporation of ergosterol into fungal cell membranes.
Forms “pores” and allows leakage of cellular contents.
Bacteria are not susceptible because they lack ergosterol.
How do you administer Ambisome?
It has distribution pretty much everywhere except…..?
So in cases that involve this area, you’d use what alternative drug?
IV
Can’t penetrate BBB.
FLUCONAZOLE penetrates the BBB. Flucytosine too?
