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Flashcards in Anti-fungals Deck (47):
1

differentiate b/w fungi in the imperfect and perfect states

imperfect: only asexual spores
perfect: sexual spores (can be induced from imperfect)

2

describe fungi characteristics

-molds: tubular hyphae
-dimorphic: yeast in host, mold at room temp
-nonmotile, rigid cell wall (chitin, polysaccharides)

3

are fungal infections transmissible person to person?

no- except scalp ringworm or neonatal thrush

4

four disease states with fungal infections

1. dermatomycoses
2. onychomycoses
3. systemic
4. mucous membranes

5

briefly describe dermatomycoses

live on keratinized tissue (skin, hair, nails)
sx: itching, burning, skin cracking

6

briefly describe onychomycoses

nail/nail bed
caused by a dermatophyte
sx: nail thickens, discolored (white/yellow/brown)

7

what drugs are used to treat dermatomycoses?

1. tolnaftate (tinactin)
2. clotrimazole (lotrimin)
3. griseofulvin

8

tolnaftate (tinactin) MOA

inhibits fungal squalene epoxidase - decreases ergosterol synthesis (for cell membrane)

9

what are some other squalene epoxidase inhibitors?

terbenafine
naftifine
butenafine

10

clotrimazole (lotrimin) MOA

azole drug: inhibits cyt p450, blocking 14a-demethylation of lanosterol to ergostanol

11

can clotrimazole react with human cells?

yes- although it is much more selective for fungi

12

two other azole antifungals besides clotrimazole

miconazole
ketoconazole

13

what is griseofulvin used for?

systemic treatment of dermatomycoses

14

griseofulvin MOA

disrupts mitotic spindle by binding polymerized microtubules to inhibit mitosis

15

what does griseofulvin treat?

onychomycoses: deposited in the newly formed keratin, where it prevents fungal growth

old nail can still have persistent infection, so therapy may last for up to or more than 1y

16

chemical properties of griseofulvin that are limiting? how do we get around these problems?

water insoluble
-use microsize and ultramicrosize particles to increase dissolution rate
-taken w/ high fat diet to increase absorption

17

AE of griseofulvin

photosensitivity
hypersensitivity
headache

18

what are 6 systemic antifungals?

1. Amphotericin B (fungizone)
2. 5-fluorocytosine (ancoban, flucytosine)
3. Ketoconazole (Nizoral)
4. Fluconazole (Diflucan)
5. Itraconazole
6. Echinocandins

19

chemical properties of ampho B

-amphoteric
-poor water solubility - not absorbed well from GI (so given IV slow infusion or as liposomal suspension injection)
-bile salt complex form = deoxycholate complex
-sterile lyophilized form = cholesterol complex

20

SE of ampho B

-major acute rxn: fever/chills
-headache, nausea, vomit, nephrotoxicity, hypotension
-limiting toxicities: nephrotoxicity + hypokalemia

21

what is the drug of choice for life-threatening fungal infections?

ampho B (broad spec- can do deep mycoses)

22

ampho B MOA

binds ergosterol in membranes, opens pores - leakage of ions and small organic molecules

23

why does ampho B cause some toxicity?

it also binds some cholesterol

24

5-fluorocytosine MOA

bacteria convert 5-fluorocytosine to 5-fluorouracil to 5-fluorodeoxyuridine monophosphate - this inhibits thymidylate synthase, inhibiting DNA synthesis

25

alternate 5-fluorocytosine MOA

antimetabolite - 5-fluorouracil incorporated into RNA in place of uracil, inhibiting protein synthesis

26

why does 5-fluorocytosine not affect human cells?

humans have little or no cytosine deaminase activity

27

5-fluorocytosine uses

-combined w/ ampho B - systemic candida, cryptococcus, meningitis
-also for Torulopsis glabrata, Cladosporium, Aspergillus

28

PK of 5-fluorocytosine

-well absorbed in GI + penetrates CSF
-low toxicity

29

toxicity of 5-fluorocytosine

-depress bone marrow fxn: leukopenia, thrombycytopenia
-careful w/ patients w/ impaired renal fxn
-nausea, vomit, diarrhea, rash, enterocolitis

30

uses of ketoconazole

-oral use for systemic infections
-tx: blastomycosis, histoplasmosis, coccidioidomycosis, paracoccidioidomycosis

31

PK of ketoconazole vs. ampho B

better tolerated than ampho B, but less effective

32

what kind of drug is fluconazole?

triazole (3 N's in a 5-membered ring)

33

PK of fluconazole

high bioavailability + penetrates CSF

34

AE and DDI with fluconazole?

decreased incidence b/c more selective for fungi
-rare: hepatotoxicity (monitor if abnormal liver fxn tests)

35

fluconazole uses

-IV: AIDS cryptococcal meningitis
-200 mg daily for prevention of crypto meningitis relapse controlled by ampho B
-150 mg p.o.- vaginal candidiasis

36

what is itraconazole a mixture of?

1:1:1:1 of 4 diastereomers
also a triazole

37

PK of itraconazole

more than 90% bound to serum proteins
extensively bound in tissues
does NOT go to CSF

38

itraconazole uses

-itraconazole > ketoconazole for nonmeningeal histo
-AIDS disseminated histo w/ stabilization during ampho B therapy

39

at what dose is itraconazole well tolerated?

200 mg/d

40

AE of itraconazole

-400 mg/d: some GI distress
-nausea, vomit, hypokalemia, rash
-rare hepatotoxicity

41

what patients should not receive itraconazole?

CHF patients b/c it can cause heart failure

42

DDI with itraconazole

DDI if given with other drugs metabolized by cyt p450, including:
-cisapride
-pimozide
-quinidine
-dofetilide

43

echinocandins MOA

inhibits 1,3-B glucan synthesis in fungal cell wall by noncompetitive inhibitin of 1,3-B glucan synthase
(selective for fungus)

44

uses of echinocandins

-broad spec w/ no cross resistance
-synergistic w/ voriconazole and ampho B

45

echinocandin admin

IV

46

AE of echinocandins

hepatotoxicity
sensitivity/allergies

47

examples of echinocandins (3)

Caspofungin (Cancidas)
Anidulafungin (Erixis)
Micafungin (Mycamine)