Anti-Fungal Pharm

Question 1

MOA amphotericin B

Answer 1

forms complex with ergosterol and disrupts plasma membrane permeability (forms pores)

Question 2

what organisms does amphotericin B fight against

Answer 2

CC(yeasts), HBC(endemic mycoses), AA(pathogenic molds)
- Candida albicans
• Cryptococcus neoformans
• Histoplasma capsulatum 
• Blastomyces dermatitidis 
• Coccidioides immitis
• Aspergillus fumigatus
• Agents of mucormycosis

Question 3

resistance to amphotericin B

Answer 3

• decreased ergosterol

- modified ergosterol (less affinity for amphotericin B)

Question 4

when to give IV amphotericin B

Answer 4

systemic infections for wide distributions

- fungal meningitis

Question 5

when to give oral amphotericin B

Answer 5

fungi in GI lumen

Question 6

adverse effects amphotericin B

Answer 6

• fever, chills, muscle spasms, vom, HA, hypotension
• renal damage
• anemia
• seizures

Question 7

how to prevent adverse effects amphotericin B

Answer 7

premedication with corticosteroids, antipyretics, antihistamines, or meperidine

Question 8

MOA flucytosine

Answer 8

flucytosine –> cytosine permease –> FdUMP and FUTP –> FdUMP inhibits DNA synthesis, FUTP inhibits RNA synthesis

Question 9

what organisms does flucytosine fight against

Answer 9

• C. neoformans
• some candida
• dematiaceous molds that cause chromoblastomycosis

Question 10

resistance to flucytosine

Answer 10

altered metabolism of flucytosine

Question 11

how is flucytosine administered

Answer 11

oral only (in US)
- widely distributes in body including CNS

Question 12

adverse effects flucytosine

Answer 12

• bone marrow toxicity (anemia, leukopenia, thombocytopenia)

- derangement of liver enzymes

Question 13

MOA of azoles

Answer 13

reduction of ergosterol synthesis by inhibiting fungal CYP450

Question 14

what organisms do azoles fight against

Answer 14

broad spectrum

• many candida
• c. neoformans
• endemic mycoses
• dermatophytes
• aspergillus

Question 15

resistance to azoles

Answer 15

upregulation of fungal CYP350

Question 16

adverse effects azoles

Answer 16

• minor GI symptoms
• can cause abnormalities in liver enzymes
• some drug-drug interactions

Question 17

adverse effects ketoconazole

Answer 17

greater propensity to inhibit mammalian cytochrome P450 and less selective for fungal P450 enzymes
- rarely used

Question 18

adverse effects of sukassazole

Answer 18

somi’s dumb

Question 19

what fungi does itraconazole specifically treat

Answer 19

• dimorphic fungi (histoplasma, blastomyces, sporothrix)
• aspergillus sp
• dermatophytes and onchomycosis

Question 20

what is the azole choice for invasive aspergillosis

Answer 20

voriconazole

Question 21

benefits of fluconazole

Answer 21

• high oral availability
• good CSF penetration
• drug interactions less common
• lease effect of all azoles on hepatic enzymes

Question 22

azole choice of treatment for secondary prophylaxis of cryptococcal meningitis

Answer 22

fluconazole

Question 23

most commonly used tx for mucocutaneous candidiasis

Answer 23

fluconazole

Question 24

can fluconazole be used against aspergillosis

Answer 24

nope, no activity against it or other filamentous fungi

Question 25

toxicities from voriconazole

Answer 25

- rash - elevated hepatic enzymes - visual disturbances - photosensitivity dermatitis

Question 26

what changes in dose of other drugs need to occur when prescribing voriconazole or posaconazole

Answer 26

there needs to be a dose reduction in meds metabolized by CYP3A4 because voriconazole and posaconazole inhibit mammalian CYP3A4 (cyclosporine, tacrolimus, statins)

Question 27

broadest spectrum of all azoles

Answer 27

posaconazole

Question 28

only azole with significant activity against mucormycosis

Answer 28

posaconazole

Question 29

when is posaconazole used as prophylaxis

Answer 29

- during induction chemotherapy for leukemia | - in allogenic bone marrow transplant pts

Question 30

MOA of echinocandins

Answer 30

inhibit synthesis of beta (1-3)-glucan at fungal cell wall by inhibiting glucan synthase

Question 31

spectrum of activity for echinocandins

Answer 31

- candida - aspergillus - NO coverage C. neoformans or agents of zygomycosis/mucormycosis

Question 32

what fungi does caspofungin (an echinocandin) specifically treat

Answer 32

- disseminated and mucocutaneous candidal infections - empiric anti-fungal therapy during febrile neutropenia - invasive aspergillosus

Question 33

what fungi does micafungin (an echinocandin) specifically treat

Answer 33

- mucocutaneous candidiasis - candidemia - prophylaxis of candidal infections in bone marrow transplant pts

Question 34

what fungi does anidulafungin (an echinocandin) specifically treat

Answer 34

- esophageal candidiasis and invasive candidiasis

Question 35

how are each echinocandin administered and what is their half life

Answer 35

only parenteral administration (IV) - caspofungin: 9-11 hours - micafungin: 11-15 hours - anidulafungin: 24-48 hours

Question 36

adverse effects echinocandins

Answer 36

- well tolerated | - minor GI stuff