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CMBM exam 4 > Antifungal Drugs > Flashcards

Antifungal Drugs Flashcards

1
Q

What fungi are superficial?

A

Dermatophytes

Malassezia furfur

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2
Q

What fungi are subcutaneous?

A

Sporothrix schenckii

Basidiobolus ranierum

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3
Q

What fungi are primary systemic?

A

Histoplamsa capsulatum
Blastomyces dermatitidis
Coccidioides immits
Paracoccidiodes brasiliensis

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4
Q

What fungi are primary opportunistic?

A 
Candida albicans
Cryptococcus neoformans 
Aspergillus fumigatus
Mucor/Rhizopus 
Pneumocystis jirovecii
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5
Q

What are the possible structures in a fungus that a drug could target?

A 
Cell membrane (ergosterol) 
Cell wall (chitin, glucan, mannan)
Nucleus
Vacuole
Cytoplasm
Mitochondria
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6
Q

What antifungal inhibit cell wall (glucan) synth?

A

Echinocandins

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7
Q

What antifungals inhibit cell membrane (ergosterol) synth?

A

Polyene

Azoles

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8
Q

What antifungals RNA/DNA synth by the pyrimidine sythesis?

A

Flucytosine

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9
Q

What are the characteristics of the optimal antifungal?

A 
Wide spectrum of activity
Favorable bioactivity
Adequate in vivo efficacy
High therapeutic index 
Low cost
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10
Q

What are the polyenes?

A

Amphotericin B and Nystatin

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11
Q

What is the action of polyenes against fungi?

A

Binds to ergosterol to form a pore making the membrane leaky

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12
Q

Describe the structure of a polyene.

A

A large lactone ring with conjugated double bond with a lipophillic side and a hydrophillic side

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13
Q

What is amphotericin B produced by?

A

Streptomyces nodosus

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14
Q

In the cell membrane, what does amphotericin cause to happen?

A

Causes a leakage of NA+, K+ and Ca+2

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15
Q

Is amphotericin B a broad spectrum fungicidal?

A

Yes

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16
Q

How would you administer amphotericin B to a pt?

A

Intravenous ONLY

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17
Q

Why doesn’t amphotericin B work well in oral form?

A

It’s highly unstable in the GI and wants to be bound to serum proteins so it works better in the blood
Lipsomal amp-B exists for oral but its expensive

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18
Q

What adverse effects could amp-B have?

A

Binds to host cell of cholesterol causing the affinity to lessen and becoming toxic
The injection might hurt
Could cause acute chills, fever and vomiting
Could chronically cause nephrotoxicity

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19
Q

What is nystatin produced by?

A

Streptomyces noursei

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20
Q

Which polyenes are used for a local infection and which is used for severe fungal infections?

A

Nyastin for local

Amp-b for severe

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21
Q

How should nystatin be administered?

A

Topical cream or as a mouth wash (oral thrush)

22
Q

How is an azole composed?

A

5-membered azole ring with at least one non-carbon atom

Classified by the number of nitrogen

23
Q

Are azoles broad spectrum antifungals?

A

Yes

24
Q

What is the mechanism for azoles?

A

Inhibits ergosterol synthesis by inhibition of CYP450

25
Q

What could happen if an azole interacts with a human CYP450?

A

Drug detox could be impaired

Steroid hormone biosynth in adrenal gland could be impaired

26
Q

What would you call an azole with two nitrogens? And what are some examples?

A

Imidazole

Ketoconazole and Miconazole

27
Q

What would an azole be called if it had 3 nitrogens? And what are some examples?

A

Triazole

Itraconazole, Fluconazole, Clotrimazole and Voriconazole

28
Q

What azole is effective against candida?

A

Voriconazole

29
Q

What are the properties of Ketoconazole (KCZ)?

A

Broad spectrum
PO administration
Mostly replaced by fluconazole

30
Q

What are the side effects of Ketoconazole?

A

Gynocomastia and hepatic failure

31
Q

What are the properties of Miconazole?

A

Topical and vaginal suppositories

Dermatophytes

32
Q

What are the properties of Clotrimazole?

A

Topical and vaginal suppositories

33
Q

What are the properties of Fluconazole (FCZ)?

A

Oral, esophageal and vaginal candidas
Generally used post initial treatment with amp-b
Used for cryptococcal meningitis
Oral and IV

34
Q

What are the properties of Itraconazole (ICZ)?

A

Broad spectrum inclusing tinea unguium
Indicated for systemic fungal infections
Also for oral and esophageal candidiasis

35
Q

What are the properties of Voriconazole (VCZ)?

A

Oral and IV
High bioavailability
Indicated for invasive aspergillosis

36
Q

Azole have very excellent _____ penetration.

A

CSF

37
Q

What is the action of allylamine?

A

Inhibit squalene expoidase to dec erogsterol synthesis

38
Q

What type of fungal infections do allylamines work against?

A

Superficial

39
Q

How are allylamines administered?

A

Oral and topical

40
Q

How do flucytosines work?

A

Blocks DNA and RNA synth

41
Q

How are flucyosines adminstered and where do they penetrate the best?

A

Oral, CSF

42
Q

What are flucyosines used against?

A

Candida and Cryptococcus neoformans

43
Q

What is the mechanism of actions for flucyosines?

A

Cyostine specific permases
Converted to 5Fdump to distrucpt DNA
Converted to 5FUMP to disrupt RNA

44
Q

What are echinocandins (caspofungin) produced from?

A

Glarea lozoyensis

45
Q

How do you administer echinocandins?

A

IV

46
Q

What is the mechanism of action for echinocandin?

A

Inhibits 1,3-B-glucan synthase

Cell wall synth inhibitor

47
Q

What are echinocandins used for?

A

Invasive amp-B resistant aspergillosis
Esophageal candidiasis
Pneumocystis pneumonia

48
Q

What is grieofulvin isolated from?

A

Pencillium griseofulvum

49
Q

How does grieofulvin work?

A

Binds to fungal tubulin which interferes with microtubular function

50
Q

What is grieofulvin highly effective against?

A

Athlete’s foot and other taenia infections

51
Q

What are the side effects of grieofulvin?

A

Teratogenic and inc CYP450 metabolism

CMBM exam 4 (27 decks)

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