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Pharm > Anti-fungals > Flashcards

Anti-fungals Flashcards

1
Q

differentiate b/w fungi in the imperfect and perfect states

A

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

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2
Q

describe fungi characteristics

A
  • molds: tubular hyphae
  • dimorphic: yeast in host, mold at room temp
  • nonmotile, rigid cell wall (chitin, polysaccharides)
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3
Q

are fungal infections transmissible person to person?

A

no- except scalp ringworm or neonatal thrush

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4
Q

four disease states with fungal infections

A
  1. dermatomycoses
  2. onychomycoses
  3. systemic
  4. mucous membranes
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5
Q

briefly describe dermatomycoses

A

live on keratinized tissue (skin, hair, nails)

sx: itching, burning, skin cracking

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6
Q

briefly describe onychomycoses

A

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

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7
Q

what drugs are used to treat dermatomycoses?

A
  1. tolnaftate (tinactin)
  2. clotrimazole (lotrimin)
  3. griseofulvin
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8
Q

tolnaftate (tinactin) MOA

A

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

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9
Q

what are some other squalene epoxidase inhibitors?

A

terbenafine
naftifine
butenafine

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10
Q

clotrimazole (lotrimin) MOA

A

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

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11
Q

can clotrimazole react with human cells?

A

yes- although it is much more selective for fungi

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12
Q

two other azole antifungals besides clotrimazole

A

miconazole

ketoconazole

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13
Q

what is griseofulvin used for?

A

systemic treatment of dermatomycoses

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14
Q

griseofulvin MOA

A

disrupts mitotic spindle by binding polymerized microtubules to inhibit mitosis

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15
Q

what does griseofulvin treat?

A

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

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16
Q

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

A

water insoluble

  • use microsize and ultramicrosize particles to increase dissolution rate
  • taken w/ high fat diet to increase absorption
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17
Q

AE of griseofulvin

A

photosensitivity
hypersensitivity
headache

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18
Q

what are 6 systemic antifungals?

A
  1. Amphotericin B (fungizone)
  2. 5-fluorocytosine (ancoban, flucytosine)
  3. Ketoconazole (Nizoral)
  4. Fluconazole (Diflucan)
  5. Itraconazole
  6. Echinocandins
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19
Q

chemical properties of ampho B

A
  • 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
Q

SE of ampho B

A
  • major acute rxn: fever/chills
  • headache, nausea, vomit, nephrotoxicity, hypotension
  • limiting toxicities: nephrotoxicity + hypokalemia
21
Q

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

A

ampho B (broad spec- can do deep mycoses)

22
Q

ampho B MOA

A

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

23
Q

why does ampho B cause some toxicity?

A

it also binds some cholesterol

24
Q

5-fluorocytosine MOA

A

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

25
Q

alternate 5-fluorocytosine MOA

A

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

26
Q

why does 5-fluorocytosine not affect human cells?

A

humans have little or no cytosine deaminase activity

27
Q

5-fluorocytosine uses

A
  • combined w/ ampho B - systemic candida, cryptococcus, meningitis
  • also for Torulopsis glabrata, Cladosporium, Aspergillus
28
Q

PK of 5-fluorocytosine

A
  • well absorbed in GI + penetrates CSF

- low toxicity

29
Q

toxicity of 5-fluorocytosine

A
  • depress bone marrow fxn: leukopenia, thrombycytopenia
  • careful w/ patients w/ impaired renal fxn
  • nausea, vomit, diarrhea, rash, enterocolitis
30
Q

uses of ketoconazole

A
  • oral use for systemic infections

- tx: blastomycosis, histoplasmosis, coccidioidomycosis, paracoccidioidomycosis

31
Q

PK of ketoconazole vs. ampho B

A

better tolerated than ampho B, but less effective

32
Q

what kind of drug is fluconazole?

A

triazole (3 N’s in a 5-membered ring)

33
Q

PK of fluconazole

A

high bioavailability + penetrates CSF

34
Q

AE and DDI with fluconazole?

A

decreased incidence b/c more selective for fungi

-rare: hepatotoxicity (monitor if abnormal liver fxn tests)

35
Q

fluconazole uses

A
  • IV: AIDS cryptococcal meningitis
  • 200 mg daily for prevention of crypto meningitis relapse controlled by ampho B
  • 150 mg p.o.- vaginal candidiasis
36
Q

what is itraconazole a mixture of?

A

1:1:1:1 of 4 diastereomers

also a triazole

37
Q

PK of itraconazole

A

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

38
Q

itraconazole uses

A
  • itraconazole > ketoconazole for nonmeningeal histo

- AIDS disseminated histo w/ stabilization during ampho B therapy

39
Q

at what dose is itraconazole well tolerated?

A

200 mg/d

40
Q

AE of itraconazole

A
  • 400 mg/d: some GI distress
  • nausea, vomit, hypokalemia, rash
  • rare hepatotoxicity
41
Q

what patients should not receive itraconazole?

A

CHF patients b/c it can cause heart failure

42
Q

DDI with itraconazole

A

DDI if given with other drugs metabolized by cyt p450, including:

  • cisapride
  • pimozide
  • quinidine
  • dofetilide
43
Q

echinocandins MOA

A

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

44
Q

uses of echinocandins

A
  • broad spec w/ no cross resistance

- synergistic w/ voriconazole and ampho B

45
Q

echinocandin admin

A

IV

46
Q

AE of echinocandins

A

hepatotoxicity

sensitivity/allergies

47
Q

examples of echinocandins (3)

A

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

Pharm (19 decks)

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