antifungals

Question 1

two examples of yeast

Answer 1

candida and cryptococcus

Question 2

examples of molds

Answer 2

aspergillus, fusarium, mucorales

Question 3

endemic mycoses?

Answer 3

histoplasma, coccidioides, blastomyces. pneumocystis jirovecii

Question 4

examples of triazoles

Answer 4

fluconazole, itraconazole, voriconazole, posaconazole

Question 5

examples of the polyenes

Answer 5

amphotericin B, nystatin

Question 6

examples of the echinocandins

Answer 6

caspofungin, micafungin, anidulafungin

Question 7

what is the mechanism of the triazole

Answer 7

impedes ergosterol synthesis through direct inhibition of cytochrome p450 dependent 14-alpha-sterol-demethylse. this causes a deficiency of ergosterol in the membrane of the fungal cells and inhibits growth. there is collection of toxic sterols in the membrane as well

Question 8

what is the most potent of the triazoles?

Answer 8

posaconazole works on almost everything

Question 9

what are itraconazole and voriconazole useful against

Answer 9

aspergillus (broad), candida, cryptococcus, endemic mycoses

Question 10

what is fluconazole used for

Answer 10

some candida, cryptococcus and endemic mycoses

Question 11

name the triazoles from most effective to least

Answer 11

posaconazole, voriconazole, itraconazole, fluconazole

Question 12

what are the SE of the triazole

Answer 12

relatively safe. liver enzyme abnorms, GI SE. voriconazole can cause visual disturbances

Question 13

what does voriconazole cause as a unique side effect

Answer 13

visual disturbances.

Question 14

do triazoles cause drug interactions? how?

Answer 14

yes. they are potential inhibitors of the CYP450. agents within the class differ in their ability to do this

Question 15

what has the least drug interactions of the triazoles

Answer 15

fluconazole

Question 16

how to treat susceptible candidiasis

Answer 16

fluconazole

Question 17

how to treat severe thrush/esophageal candidiasis

Answer 17

fluconazole

Question 18

how to prophylax for cryptococcal meningitis

Answer 18

fluconazole

Question 19

what is used as secondary treatment or the prophylaxis of histoplasmosis

Answer 19

itraconazole

Question 20

what treatment for invasive aspergillus

Answer 20

voriconazole

Question 21

what to prophylax for aspergillus/candidiasis in immunocompromised patients

Answer 21

posaconazole

Question 22

what common drug interaction occurs with itraconazole

Answer 22

diltiazem CCB. might have to lower the dose.

Question 23

what is another common drug interaction for itraconazole

Answer 23

ritonavir inhibits the metabolism of itraconazole significantly

Question 24

what class is amphotericin B

Answer 24

polyene macrolide.

Question 25

what is the mechanism of amphotericin

Answer 25

inhibition of ergosterol -generates pores in the fungal membrane.

Question 26

what is amphotericin B active against

Answer 26

candida, aspergillus, zygomyces, histoplasma, cryptococcus

Question 27

what is negative about amphotericin

Answer 27

there is a large SE profile. many patients unable to tolerate.

Question 28

what is the most important SE of amphotericin

Answer 28

nephrotoxicity. must watch the Cr.

Question 29

what are the acute infusion related SE of amphotericin

Answer 29

fever, chills, rigor. needs premedication

Question 30

what do we premedicate with for amphotericin treatment

Answer 30

diphenhydramine, APAP, meperidine

Question 31

what are the electrolyte abnormalities for amphotericin B

Answer 31

hypokalemia, hypomag

Question 32

what is the solution to the side effects of amphotericin

Answer 32

lipid formulations give better tolerability and are more renal protective with less infusion related SE> they allow to push higher doses in a safer manner.

Question 33

downfall to amphotericin B lipid formulation

Answer 33

expensive and still toxic

Question 34

what three agents are in the class echinocandins

Answer 34

caspofungin, micofungin, anidulafungin

Question 35

what are the echinocandins used to treat

Answer 35

candida, refractory aspergillus, esophageal candida, empirical antifungal for neutropenic patients.

Question 36

what is the unique machanism of action for caspofungin

Answer 36

inhibits the enzyme beta-1,3 D glucan synthase. a component of the cell wall not found in mammalian species. it is useful aspergillus and candida sps

Question 37

what are the positives for echinocandins

Answer 37

very few side effects, hapatically eliminated (liver toxic possible), few interactions, excellent activity against candida including the azole resistant. it also has good activity against molds.

Question 38

flucytosine is chemically related to what?

Answer 38

5 fluorouracil

Question 39

what is the mechanism of action for flucytosine

Answer 39

pyrimidine analog that inhibits DNA and RNA synthesis. only available as an oral formulation

Question 40

what is the spectrum of activity for flucytosine

Answer 40

narrow. used clinically only with other antifungals particularly with amphotericin B.

Question 41

what is flucytosine active against

Answer 41

cryptococcus and candida

Question 42

why is flucytosine not used as monotherapy

Answer 42

because resistance forms quickly

Question 43

what is flucytosine and amphotericin B commonly used against

Answer 43

cryptococcus meningitis

Question 44

what are the adverse of flucytosine

Answer 44

bone marrow toxicity, leukopenia, anemia, thrombocytopenia. liver dysfunction possible, GI intolerances. these are concentration dependent.