Antifungals

Question 1

what are the three major categories of pathogenic fungus

Answer 1

yeast, molds, other (endemic mycoses, pneumocystis jiroveci)

Question 2

what can you target on the fungal structure?

Answer 2

cell walls made of ergosterol. Beta 1,3 glucan synthase, an enzyme that makes cell walls

Question 3

list the 4 triazole antifungals

Answer 3

fluconazole, itraconazole, posaconazole, voriconazole

Question 4

triazole mechanism of action

Answer 4

impede ergosterol synthesis through direct inhibition of P450 dependent enzyme 14-alpha-sterol-demthylase. stops fungal growth

Question 5

what is the most potent triazole

Answer 5

posaconazole

Question 6

triazole adverse effects

Answer 6

pretty safe. liver enzyme abnormalities, monitor if long term treatment. GI side effects. Voriconazole causes visual disturbances

Question 7

triazole drug interactions

Answer 7

all triazoles are substrates and potential inhibitors of CYP450. important to assess for drug interactions! fluconazole has lowest drug interaction potency

Question 8

what does fluconazole treat

Answer 8

susceptible candidiasis. severe thrush/candidiasis.

Question 9

what does itraconazole treat

Answer 9

secondary treatment and prophylaxis of systemic histoplasmosis

Question 10

what does voriconazole treat

Answer 10

invasive aspergillosis

Question 11

what does posaconazole treat

Answer 11

prophylaxis of aspergillosis/candidiasis in immunocompromised people

Question 12

amphotericin B mechanism of action

Answer 12

travels across cell wall and inserts into the cell wall. pulls it apart to create pores

Question 13

adverse effects with amphotericin B

Answer 13

nephrotoxicity! watch serum creatinine. Acute infusion related reactions such as chills, fever, rigors. Electrolyte abnormalities. many patients unable to tolerate full course of conventional amphotericin B

Question 14

how do we make amphotericin B have less side effects?

Answer 14

lipid formulations. more renal protective. less infusion related side effects. putting it in lysosomes gets it taken up by the fungus, not the rest of the body!

Question 15

echinocandin agents

Answer 15

caspofungin, micafungin, anidulafungin

Question 16

what are the echinocandins used for?

Answer 16

candida infections, refractory aspergillus, esophageal candidiasis, empiric antifungal for febrile neutropenic patients

Question 17

echinocandin mechanism of action

Answer 17

inhibits beta 1,3 glucan synthase. prevents making of the cell wall and destroys the cell. works well on yeast, less so on molds

Question 18

what do echinocandins have great activity against?

Answer 18

excellent against candida!

Question 19

flucytosine mechanism of action

Answer 19

pyrimidine analogue that inhibits DNA and RNA synthesis. only oral formulation

Question 20

flucytosine spectrum of activity

Answer 20

active against cryptococcus and some candida species. clinically only used in combos!

Question 21

flucytosine adverse effects

Answer 21

similar to a chemo drug. bone marrow toxicity. liver dysfunction possible. GI intolerances