Systemic Antifungal

Question 1

Major categories of pathogenic fungi:

Answer 1

Yeast: candida, cryptococcus;
Molds: aspergillus, fusarium, mucorales;
Other:
endemic mycoses like histooplasma, coccidioides, blastomyces, 
and pneumocystic jiroveci

Question 2

Fungal cell membranes have ____ for; what is the difference between our cells and theirs?

Answer 2

sterols; regulation of what goes in and out;

fungi have a cell wall

Question 3

List of triazole antifungals, MOA, thera, and SE’s:

Answer 3

Names: Fluconazole, itraconazole, posaconazole, voriconazole
MOA: impedes ergosterol synthesis through direct inhibition of cytochrome P450 dependent enzyme 14-alpha-sterol-demethylase (necessary for biosynthetic pathway of ergosterol (prevents production of new cells);
Thera:
Fluconazole has some Candida, cryptococcus, endemic mycoses
Voriconazole, itraconazole: above and aspergillus, more Candida
Posaconazole: above and fusarium, mucorales
SE’s: Relatively safe, but think liver enzyme abnormalities (hepatitis rarely, LFT monitoring for longer term); GI SE’s, visual disturbances with vori

Question 4

Which of the azoles has the lowest drug interaction potency?

Answer 4

Fluconazole

Question 5

For each of the azoles, what is the treatment of choice?

Answer 5

1. Fluconazole: susceptible candidiasis, severe thrush/esophageal candidiasis, secondary treatment and prophylaxis of cryptococcal meningitis
2. Itraconazole: secondary treatment and prophylaxis of systemic histoplasmosis
3. Voriconazole: invasive aspergillosis
4. Posaconazole: prophylaxis of aspergillosis/candidiasis in immunocompromised patients

Question 6

Itraconazole can inhibit the metabolism of _____; ritonavir can inhibit the metabolism of _______

Answer 6

diltiazem; itraconazole

Question 7

Amphotericin B: class, MOA, thera, SE’s, misc:

Answer 7

Class: polyene macrolide;
MOA: inhibition of ergosterol (generates pores; can kill existing fungal cells)
Thera: broad spectrum of fungal pathogens including Candida, Aspergillus, Zygomyces, Histoplasma, Cryptococcus
SE’s: nephrotoxicity (LOOK OUT FOR serum creatinine); fever, chills, rigors (pre-medicate with diphenhydramine, APAP, meperidine); electrolyte abnormalities (hypomagnesemia, hypokalemia)
Misc: Try lipid formulations as they are more renal protective with less infusion-related SE’s, but are more expensive with risk of toxicity;
formulations include Amphotericin B lipid complex with liposomal Amphotericin B

Question 8

Echinocandins: list, thera, SE’s:

Answer 8

List: caspofungin, micafungin, anidulafungin
Thera: candida infections, refractory aspergillus infection, esophageal candidiasis, empiric antifungal therapy for febrile Neutropenic patients (NERC)
SE’s: Hepatically eliminated (adjust dose for liver dysfunction and liver toxicity possible)
Misc: only available IV; few drug interactions; very few SE’s with no cell wall in humans; can go against azole-resistant Candida

Question 9

Flucytosine: class, MOA, thera, SE’s:

Answer 9

Class: prodrug converted to 5-FU
MOA: pyrimidine analogue that inhibits DNA and RNA synthesis;
Thera: active against cryptococcus and some Candida species; use ONLY in combo with other systemic antifungal agents (especially with amphotericin B, which can be used to treat cryptococcus meningitis)
SE’s: think chemo, bone marrow toxicity (leukopenia, thrombocytopenia, anemia, or TAL), liver dysfunction, GI intolerances
Misc: oral