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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
Q

Ketoconazole AEs

A

Adrenal insuficiency, gynegomastia, impotence, androgen synthesis inhibition

26
Q

Miconazole MOA

A

Inhiits 14α-sterol demethylase as well as fatty acid synthesis and peroxidase enzymes

27
Q

Itraconazole use

A

Broad spectrum mycoses treatment

28
Q

Itraconazole kinetics

A

Needs acidic environment for absorption, oxidized in liver to active form.

Plasma bound

29
Q

Itraconazole in meningitis

A

Doesnt penetrate CSF but can reach meninges

30
Q

Fluconazole kinetics

A

Gastric pH doesnt matter, 100% bioavilability, reaches everything (CSf, urine, saliva)

31
Q

Drug of choice for systemic candidiasis, cryptococcal meningitis and coccidiodal meningitis

A

Fluconazole

32
Q

Fluconazole resistance via

A

Mutation and overexpression of fungal P450 enzymes

33
Q

Ravuconazole spectrum

A

Expanded spectrum fluconazole, works against aspergillius

34
Q

Drug of choice for invasive aspergillosis, fusarium and scedosporium

A

Voriconazole

35
Q

Voriconazole AEs

A

Hepatic toxicity

Visual symptoms

36
Q

Terconazole

A

Vaginal suppository for vaginal candidiasis

37
Q

Amphotericin B toxicity to humans via

A

Also affects human plasma membrane sterols

38
Q

Amphotericin B MOA

A

Binds ergosterol to disrupt fungal membrane stability, forming pores

Also generates free radicals that further damage membrane

39
Q

Nyastatin MOA

A

Binds ergosterol to disrupt fungal membrane stability

40
Q

Natamycin MOA

A

Binds ergosterol to disrupt fungal membrane stability

41
Q

Polyene MOA

A

Binds ergosterol to disrupt fungal membrane stability

42
Q

Amphotericin fungicidal vs fungistatic depends on

A

Dose

43
Q

Amphotericin B AEs

A

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
Q

How to reduce amphotericin B toxicity

A

Package in liposomes/ other lipid carriers

45
Q

Nyastatin use

A

Used topically in skin, vaginal mucosa, oral mucosa

Doesn’t absorb

46
Q

Natamycin use

A

Corneal infection with aspergillus or fusarium

47
Q

Caspofungin, micafungin and anidulafungin MOA

A

Noncompetitive inhibition of β-(1,3)-D-glucans

This disrupts cell wall intergrity

48
Q

Caspofungin use

A

Empiric for febrile neutropenia

Also candidiasis

49
Q

Micafungal use

A

Esophageal candidiasis and antifungal prophylaxis in stem cell transplant

50
Q

Ciclopirox MOA.

A

Chelates Fe3+ and Al3+ which inhibits many fungal processes

51
Q

Ciclopirox use

A

Skin infections topically

PBL 2.2.5 (11 decks)

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