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PBL 2.2.5 > Pharm 36: Fungicidal Tendencies > Flashcards

Pharm 36: Fungicidal Tendencies Flashcards

1
Q

Flucystosine MOA

A

converted to 5-FdUMP within cell.

5-FdUMP inhibits thymidylate synthase, resulting in inhibtion of DNA synthesis

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2
Q

Flucytosine is fungi_____

A

Fungistatic

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3
Q

Why doesnt flucytosine affect human cells

A

No cytosine permeases expressed, drug can’t enter

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4
Q

Flycytosine used along with _____

Why?

A

Amphotericin B

Acts synergistically

Without Amphotericin, resistance emerges quickly

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5
Q

Single agent flucystosine used for

A

Candidiasis,

Cryptococcosis

Chromomycosis

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6
Q

Flucytosine tissue penetrance

A

Very high. CNS, eyes, urinary tract

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7
Q

Flucytosine AEs

A

Bone marrow suppression, hepatic dysfunction

DO NOT USE IN PREGNANCY

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8
Q

Griseofulvin MOA

A

Binds to tubilin and microtubules to disrupt mitotic spindle preventing mitosis

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9
Q

Griseofulvin is fungi___

A

Fungistatic

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10
Q

Griseofulvin accumulates in _____

A

Keratin precursor cells

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11
Q

Griseofulvin used for

A

Skin/hair/nail fungal infections

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12
Q

How to increase griseofulvin absorption

A

Eat with fatty (greasy) meal

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13
Q

Griseofulvin ____ P450

A

Enhances

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14
Q

What dose squalene epoxidase do?

A

Part of ergosterol synthesis

Converts squalene to lanosterol

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15
Q

Terbinafine MOA

A

Squalene epoxidase inhibitor

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16
Q

Terbinafine kinetics (oral)

A

Binds to plasma then goes through liver first pass metabolism.

Oral bioavailability 40%

300 hour half life

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17
Q

Terbinafine AEs

A

Hepatotoxicity, SJS, psoriasis

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18
Q

Terbinafine used for

A

Onychomycosis (nail fungus)

Use for all types of tinea

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19
Q

Terbinafine metabolism

A

Via P450

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20
Q

Naftifine MOA and use

A

Topical squalene epoxidase inhibitior

Used for tineas

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21
Q

Butenafine MOA and use

A

Squalene epoxidase inhibitors

Effective against tineas

22
Q

14a-sterol demethylase: what does it do

A

Fungal enzyme that catalyses conversion of lanosterol to ergosterol

23
Q

Azoles MOA

A

Inhibit fungal 14α-sterol demythylase.

Causes 14α-methyl to accumulate and disrupt the phospholipid membrane

Cell dies

24
Q

Azoles are fungi___

A

Fungistatic (usually)

25
Ketoconazole AEs
Adrenal insuficiency, gynegomastia, impotence, androgen synthesis inhibition
26
Miconazole MOA
Inhiits 14α-sterol demethylase as well as fatty acid synthesis and peroxidase enzymes
27
Itraconazole use
Broad spectrum mycoses treatment
28
Itraconazole kinetics
Needs acidic environment for absorption, oxidized in liver to active form. Plasma bound
29
Itraconazole in meningitis
Doesnt penetrate CSF but can reach meninges
30
Fluconazole kinetics
Gastric pH doesnt matter, 100% bioavilability, reaches everything (CSf, urine, saliva)
31
Drug of choice for systemic candidiasis, cryptococcal meningitis and coccidiodal meningitis
Fluconazole
32
Fluconazole resistance via
Mutation and overexpression of fungal P450 enzymes
33
Ravuconazole spectrum
Expanded spectrum fluconazole, works against aspergillius
34
Drug of choice for invasive aspergillosis, *fusarium* and *scedosporium*
Voriconazole
35
Voriconazole AEs
Hepatic toxicity Visual symptoms
36
Terconazole
Vaginal suppository for vaginal candidiasis
37
Amphotericin B toxicity to humans via
Also affects human plasma membrane sterols
38
Amphotericin B MOA
Binds ergosterol to disrupt fungal membrane stability, forming pores Also generates free radicals that further damage membrane
39
Nyastatin MOA
Binds ergosterol to disrupt fungal membrane stability
40
Natamycin MOA
Binds ergosterol to disrupt fungal membrane stability
41
Polyene MOA
Binds ergosterol to disrupt fungal membrane stability
42
Amphotericin fungicidal vs fungistatic depends on
Dose
43
Amphotericin B AEs
Systemic reactions: cytokine storm (fever, hypotension) Renal: significant renal toxicity. Discontinue if BUN or creatinine rise too much. Hypokalemia common Hematologic: anemia b/c decreased erythropoietin
44
How to reduce amphotericin B toxicity
Package in liposomes/ other lipid carriers
45
Nyastatin use
Used topically in skin, vaginal mucosa, oral mucosa Doesn’t absorb
46
Natamycin use
Corneal infection with *aspergillus* or *fusarium*
47
Caspofungin, micafungin and anidulafungin MOA
Noncompetitive inhibition of β-(1,3)-D-glucans This disrupts cell wall intergrity
48
Caspofungin use
Empiric for febrile neutropenia Also candidiasis
49
Micafungal use
Esophageal candidiasis and antifungal prophylaxis in stem cell transplant
50
Ciclopirox MOA.
Chelates Fe3+ and Al3+ which inhibits many fungal processes
51
Ciclopirox use
Skin infections topically

PBL 2.2.5 (11 decks)

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