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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
Often seen in HIV
Cryptococcus neoformans
26
DOC of cryptococcus neoformans
Ampho B + Flucytosine (CNS penetration)
27
Good CNS penetration
Flucytosine | Some: Voriconazole
28
Toxicity of flucytosine
depression of bone marrow (anemia, leukopenia, thrombocytopenia) GI may elevate ALT or AST (may be reversible)
29
Kinetics of flucytosine
well absorbed orally enters CFS and aqueous humor renal elimination (renal impairment can lead to toxicity)
30
Azole MOA
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
31
Cidal antifungals
ampho B, flucytosine
32
Static antifungals
azoles
33
Spectrum of azoles
broad; oral widely distributed in body, largely bound to plasma albumin, CNS penetration is low extensively metabolized prior to elimination (hepatic)
34
Toxicity of ketoconazole
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
Inhibitors of P450 (3)
Ketoconazole,
36
Contraindications for ketoconazole
acute or chronic hepatic disease
37
Administration of ketoconazole
shampoo (oral only if no anitfungal can be used)
38
Fluconazole
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
Toxicity of fluconazole
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
Voriconazole
IV, oral Modest CSF hepatic elimination DOC for aspergillus
41
DOC for aspergillus
Voriconazole + ampho B
42
Voriconazole use
ASPERGILLUS salvage therapy esophageal candidiasis
43
Drug interactions of Voriconazole
metabolized by P450's Inhibits P450's; drug interaction with itself Generic polymorphis of CYP2C19: extensive vs. poor metabolizers
44
Toxicty of voriconazole
changes in visual field, acuity, photophobia, color/light perception (TAKE OFF DRUG)
45
Itraconazole
spectrum: similar to fluconazole, but greater activity to Aspergillus Oral, IM
46
Adverse rxn to itraconazole
GI, N/V, diarrhea, abdominal pain | Potent inhibitor of CYP3A4
47
Bioavailability of itraconazole
Capsules vs. oral solution (DON"T INTERCHANGE)
48
Isavuconazonium spectrum
mucormycosis and invasive aspergillosis (orphan drug status); aspergilus sp, Mucor sp, Rhizpus sp
49
Kinetics of Isavuconazonium
IV, oral Hepatic elimination Substrate and moderate inhibitor of CYP3A4 (drug interactions)
50
Toxicity of Isavuconazonium
nephrotoxic dose dependent decrease in QT interval (contraindication) NEW DRUG
51
Posaconazole
Aspergillus and canidida IV, oral substrate and inhibitor of CYP3A4 Toxic: GI, stomatitis, vaginal bleeding, hypokalemia, thrombocyptoenia
52
Echinocandins MOA
inhibit syntehsis of major fungal cell wall component, Beta-(1,3)-D-Glucan (not in mammalian cells)
53
Echinocandins
IV (slow infusion) cell death (PCN of antifungals) lack nephrotoxicity and few drug interactions indicated for treatment of invasive aspergillosis in refractory patients
54
Echinocandins adverse sx
Effects: Increased liver enzymes, histamine release, H/A, Chills
55
Similar drugs to echinocandins
micafungin and anidulafungin
56
Topical/Local antigunfals
griseofulvin Terbinafine nystatin (all taken orally or topically)
57
Dermatophytosis
fungal infection that affects diff. parts of the body; caused by dermatophytes; invade and feed on keratin
58
Onychoycosis
ringworm of the nail Effects toenails or fingernails caused by dermatophytes, candida, and nondermatophytc molds
59
Griseofulvin MOA
binds to microtubles of fungi and destroys mitotic spindle structure (of keratin); FUNGISTATIC
60
Use of Griseofulvin
ringworm (dermatophytosis) of skin hair and nails
61
DOC for onychomycosis
Griseofulvin (binds to keratin to treat)
62
Administration of griseofulvin
ONLY ORAL (no topical)
63
Tx time for griseofulvin
6 mo-1 year (keratin can be replaced)
64
Excretion of griseofulvin
unchanged in feces
65
Toxicity of griseofulvin
HEADACHE DISULFIRAM-LIKE Heme distrubance, rashes, photosensitivity, angioedema, albuminuria, hepatotoxicity, leukopenia
66
Contraindications of griseofulvin
acute intermittent porphyria hepatocellular failure pregnancy and men 6 months prior to fathering a child
67
Terbinafine
``` oral or topical effective for onychomycosis (not DOC) well absorbed, concentrates in nail FUNGICIDAL less active for candida ```
68
Terbinafine MOA
interferes with sterol biosynthesis; inhibits squalene monooxygenase; build-up of squalene is toxic to fungal
69
Nystatin
polyene antibiotic, primarily used for Candidal infections oral/topical not absorbed from GI, skin or mucous
70
DOC of candida
Nystatin
71
Side effects of nystatin
mild to transitory N/V, diarrhea after oral use
72
Efinaconazole
newest antifungal
73
Use of efinaconazole
onychomycosis caused by tricho. rubrum and tricho, menta. | Topical solution- daily for 48 weeks
74
Cidal antifungals
Ampho B and terbinafine
75
Static antifungals
Azoles, griseofulvin
76
Potent antifungal inhibitors of CYP3A4
itraconazole, isavuconazonium, posaconazole

Pharm Exam 3 (1 decks)

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