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Pharm Exam 3 > Antifungal > Flashcards

Antifungal Flashcards

1
Q

Systemic fungal infection

A

LIFE-THREATENING

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2
Q

superficial mycoses

A

limited to outermost layer of skin/hair

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3
Q

Cuntaneous mycoses

A

extended into epidermis, include invasive hair and nail; restricted to keratinized layers of skin

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4
Q

Cutaneous mycoses examples

A

Dermatophytes (athlete’s foot, ringword, etc.)

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5
Q

Subcutaneous mycoses

A

involve dermis, subq tissue, muscle and fascie; can be caused by trauma allowing fungit to enter; difficult to treat and may require surgery

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6
Q

Systemic mycoses due to primary pathogens

A

primarily in lungs and may spread to organs

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7
Q

Systemic mycoses due to opportunistic

A

immune deficient people (ex. candidiasis, aspergillosis, cryptococcosis)

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8
Q

Target of antifungals

A

cell membrane of cell wall

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9
Q

Examples of opportunistic pathogens

A

Candida, Aspergilosis, cryptococcosis

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10
Q

Major systemic tx (DOC)

A

Amphotericin B

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11
Q

Azoles

A

Ketoconazole, fluconazole, voriconazole, itraconazole, isavuconazole, posaconazole

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12
Q

Echinocandins

A

caspofungin, micafungin, anidulafungin

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13
Q

Amphotericin B MOA

A

cidal; polyene antifungal that binds to ergosterol - results in loss of intracellular components and depolarization (pore formation)

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14
Q

Produced by Streptomyces nodosus

A

Amphotericin B

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15
Q

Spectrum of Amphotericin B

A 
broad; fungicidal
IV
Poor CNS penetration
Excreted slowly by kidney (NEPHROTOXIC)
Detected in urine for several weeks
Renal/hepatic impairement and hemodialysis have little impact on drug concentration, therefore no dose adjustment required
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16
Q

Drawback of amphotericin B

A

VERY NEPHROTOXIC (benefits outway the negatives though- still tx)

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17
Q

Toxicity of amphotericin B

A

binding to membrane sterols (accounts for toxicity) (cholesterol and ergosterol similar in structure)

Toxicity due to: infusion of drug OR reactions occuring over time

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18
Q

Infusion related toxicity of amphotericin B

A

chills, fever, muscle spasms, vomiting, H/A

lessened by slowing infusion rate and/or decreasing dose (give blanket, cortisone, aspirin)

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19
Q

Reactions over time (cumulative) to amphotericin

A

NEPHROTOXIC
Azotemia - BUN and serum creatinine levels are elevated (increased N in blood)
Other nephtrotoxic drugs given with caution (aminoglycosides)
renal damaged (dose dependent- can be irreversible)
Hepatic failure, jaundice, anorexia, N/V, weight loss, hypokalemia
Hypersensitivity
6 wks- 4 mo of treatment

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20
Q

Treatment time for amphotericin B for systemic

A

6 weeks - 4 months

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21
Q

Flucytosine MOA

A

metabolic antagonism of fungal DNA and RNA; flucytosine converted to 5-fluoroacil which interferes with fungal DNA and RNA synthesis

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22
Q

Enzyme that converted flucytosine to 5-fluoracil

A

Cytosine deaminase (bacteria have this-kills bacteria & disrupt normal flora leading to GI intolerance)

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23
Q

Prodrugs

A

Flucytosine

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24
Q

Spectrum of Flucytosine

A

lower than ampho B;
DOC: Cyrptococcus neoformans
Can also be used for: candida, aspergillus, sporotricham

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25
Q

Often seen in HIV

A

Cryptococcus neoformans

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26
Q

DOC of cryptococcus neoformans

A

Ampho B + Flucytosine (CNS penetration)

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27
Q

Good CNS penetration

A

Flucytosine

Some: Voriconazole

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28
Q

Toxicity of flucytosine

A

depression of bone marrow (anemia, leukopenia, thrombocytopenia)
GI
may elevate ALT or AST (may be reversible)

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29
Q

Kinetics of flucytosine

A

well absorbed orally
enters CFS and aqueous humor
renal elimination (renal impairment can lead to toxicity)

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30
Q

Azole MOA

A

inhibits the synthesis of ergosterol - leads to depletion of ergosterol in the cell membrane and accumulation of toxic intermediate sterols, causing increased membrane permeability and inhibition of fungal growth; FUNGISTATIC

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31
Q

Cidal antifungals

A

ampho B, flucytosine

32
Q

Static antifungals

A

azoles

33
Q

Spectrum of azoles

A

broad;
oral
widely distributed in body, largely bound to plasma albumin, CNS penetration is low
extensively metabolized prior to elimination (hepatic)

34
Q

Toxicity of ketoconazole

A

GI upset, pruritus
INHIBITOR OF P450
gynecomastia and impotence due to adrenal and testicular function (doesn’t go away)
PROLONGED CT
transient elevation of serum enzymes
dizziness, somnolence, H/A, arthalgia, myalgia, fever/chills, N/V

35
Q

Inhibitors of P450 (3)

A

Ketoconazole,

36
Q

Contraindications for ketoconazole

A

acute or chronic hepatic disease

37
Q

Administration of ketoconazole

A

shampoo (oral only if no anitfungal can be used)

38
Q

Fluconazole

A

oral, IV
penetrates well into other body fluids, particularly CSF (fungal meningitis)
Good for suppressive and/or prophylactic therapy in HIV + (If CD4 count drops)

39
Q

Toxicity of fluconazole

A

less toxic than ampho B or flucytosine and better tolerated than keto
less drug interactions than other azoles (potent inhibitor of CYP2C9
H/A (main side effect), N/V, GI, elevation in aminotransferase activity

40
Q

Voriconazole

A

IV, oral
Modest CSF
hepatic elimination
DOC for aspergillus

41
Q

DOC for aspergillus

A

Voriconazole + ampho B

42
Q

Voriconazole use

A

ASPERGILLUS
salvage therapy
esophageal candidiasis

43
Q

Drug interactions of Voriconazole

A

metabolized by P450’s
Inhibits P450’s; drug interaction with itself
Generic polymorphis of CYP2C19: extensive vs. poor metabolizers

44
Q

Toxicty of voriconazole

A

changes in visual field, acuity, photophobia, color/light perception (TAKE OFF DRUG)

45
Q

Itraconazole

A

spectrum: similar to fluconazole, but greater activity to Aspergillus
Oral, IM

46
Q

Adverse rxn to itraconazole

A

GI, N/V, diarrhea, abdominal pain

Potent inhibitor of CYP3A4

47
Q

Bioavailability of itraconazole

A

Capsules vs. oral solution (DON”T INTERCHANGE)

48
Q

Isavuconazonium spectrum

A

mucormycosis and invasive aspergillosis (orphan drug status); aspergilus sp, Mucor sp, Rhizpus sp

49
Q

Kinetics of Isavuconazonium

A

IV, oral
Hepatic elimination
Substrate and moderate inhibitor of CYP3A4 (drug interactions)

50
Q

Toxicity of Isavuconazonium

A

nephrotoxic
dose dependent decrease in QT interval (contraindication)
NEW DRUG

51
Q

Posaconazole

A

Aspergillus and canidida
IV, oral
substrate and inhibitor of CYP3A4
Toxic: GI, stomatitis, vaginal bleeding, hypokalemia, thrombocyptoenia

52
Q

Echinocandins MOA

A

inhibit syntehsis of major fungal cell wall component, Beta-(1,3)-D-Glucan (not in mammalian cells)

53
Q

Echinocandins

A

IV (slow infusion)
cell death (PCN of antifungals)
lack nephrotoxicity and few drug interactions
indicated for treatment of invasive aspergillosis in refractory patients

54
Q

Echinocandins adverse sx

A

Effects: Increased liver enzymes, histamine release, H/A, Chills

55
Q

Similar drugs to echinocandins

A

micafungin and anidulafungin

56
Q

Topical/Local antigunfals

A

griseofulvin
Terbinafine
nystatin
(all taken orally or topically)

57
Q

Dermatophytosis

A

fungal infection that affects diff. parts of the body; caused by dermatophytes; invade and feed on keratin

58
Q

Onychoycosis

A

ringworm of the nail
Effects toenails or fingernails
caused by dermatophytes, candida, and nondermatophytc molds

59
Q

Griseofulvin MOA

A

binds to microtubles of fungi and destroys mitotic spindle structure (of keratin); FUNGISTATIC

60
Q

Use of Griseofulvin

A

ringworm (dermatophytosis) of skin hair and nails

61
Q

DOC for onychomycosis

A

Griseofulvin (binds to keratin to treat)

62
Q

Administration of griseofulvin

A

ONLY ORAL (no topical)

63
Q

Tx time for griseofulvin

A

6 mo-1 year (keratin can be replaced)

64
Q

Excretion of griseofulvin

A

unchanged in feces

65
Q

Toxicity of griseofulvin

A

HEADACHE
DISULFIRAM-LIKE
Heme distrubance, rashes, photosensitivity, angioedema, albuminuria, hepatotoxicity, leukopenia

66
Q

Contraindications of griseofulvin

A

acute intermittent porphyria
hepatocellular failure
pregnancy and men 6 months prior to fathering a child

67
Q

Terbinafine

A 
oral or topical
effective for onychomycosis (not DOC)
well absorbed, concentrates in nail
FUNGICIDAL
less active for candida
68
Q

Terbinafine MOA

A

interferes with sterol biosynthesis; inhibits squalene monooxygenase; build-up of squalene is toxic to fungal

69
Q

Nystatin

A

polyene antibiotic, primarily used for Candidal infections
oral/topical
not absorbed from GI, skin or mucous

70
Q

DOC of candida

A

Nystatin

71
Q

Side effects of nystatin

A

mild to transitory N/V, diarrhea after oral use

72
Q

Efinaconazole

A

newest antifungal

73
Q

Use of efinaconazole

A

onychomycosis caused by tricho. rubrum and tricho, menta.

Topical solution- daily for 48 weeks

74
Q

Cidal antifungals

A

Ampho B and terbinafine

75
Q

Static antifungals

A

Azoles, griseofulvin

76
Q

Potent antifungal inhibitors of CYP3A4

A

itraconazole, isavuconazonium, posaconazole

Pharm Exam 3 (1 decks)

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