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Pharm exam 4 > Antifungals > Flashcards

Antifungals Flashcards

1
Q

unique targets for antifungal therapy

A

fungal cell membrane - ergosterole and ergosterol synthesis

fungal cell wall - glucans

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2
Q

shared targets for antifungals

A

DNA/RNA synthesis

cell division

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3
Q

which drugs site of action is membrane function

A

amphotericin B

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4
Q

which drugs site of action is ergosterol syntheiss

A 
Fluconazole
Itraconazole
Voriconazole
Naftifine
Terbinafine
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5
Q

which drugs site of action is nucleic acid synthesis

A

5-fluurocytosine

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6
Q

which drugs site of action is cell wall synthesis

A

caspofungin

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7
Q

systemically active drugs for systemic infections

  • oral or IV use
A

Polyenes - amphotericin B**drug of choice or alternative

Azoles - most of them

Flucytosine

Echinocandins

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8
Q

what drug has the broadest spectrum activity of all antifungals

A

amphotericin B

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9
Q

MOA of amphotericin B

A

binds to ergosterol in fungal CM

forms amp B containing pores - altering permiability

fungicidal

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10
Q

how does resistance develop to amphotericin B

A

membrane ergosterol concentration is decreased

sterol target is modified

(Candida and Aspergillus)

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11
Q

Adverse effects of amphotericin B

A

**Nephrotoxicity (most common and most serious long term toxicity)

infusion related rxns - fever, chills, muscle spasms, vomiting, HA, hyper-/hypotension

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12
Q

how can amphotericin b be made less toxic

A

liposomal packaged formulations - decrease binding to human CM

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13
Q

MOA of azoles

A

bind to enzyme responsible for converteing lanosterol to ergosterol –>”leaky” cell membrane

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14
Q

SE of azoles

A

relatively non-toxic

minor GI

interaction with P450

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15
Q

Azole:

Frist oral azole

higher degree of inhibition of cytochrome p450

lower selective toxicity

largemely replaced by newer azoles

A

ketoconazole

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16
Q

highest therapeutic index of all azoles

lowest level of interaction with p450

A

fluconazole

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17
Q

Fluconazole is the agent of choice for treating what

A

candidiasis

cryptococcosis

coccidiomycosis

2nd line for other systemic infections: histoplasmosis, blastomycosis, sporotichosis

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18
Q

what drug has a broader spectrum of activity that fluconazole but poorer pharmacology and TI

A

Itraconazole

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19
Q

what does intraconazole require for absorption

A

low gastric pH

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20
Q

does itraconazole or fluconazole penetrate the CNS

A

fluconazole

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21
Q

what does itraconazole interact with

A

hepatic microsomal enzymes - significant interaction with commonly used drugs

22
Q

what is itraconazole drug of choice for treating

A
  1. blastomycosis
  2. coccidiomycosis
  3. histoplasmosis
  4. sporotrichosis
  5. dermatophyte (onychomycosis)
23
Q

due to its lower toxicity, what drug has replaced amphotericin B as tx of chioce for asperigillosis

A

vorconazole

24
Q

spectrum of activity for voriconazole

A

Candida

Endemic dimorphic fungi

aspergillosis (tx of choice)

25
Q

SE of voriconazole

A
  • visual disturbances
  • hallucinations
  • liver enzyme abnormaliies
  • rash

*similar to other azoles inhibits cytochrome p450

26
Q

what has the broadest spectrum of activity of all azoles

A

Posaconazole

27
Q

what does posaconazol treat

A

Candida

Aspergillus

Mucormycoses

28
Q

Newer alternative therapy for invasive aspergillosis and mucromycosis

increased sollubility compared to voriconazole and posaconazole

less risk of nephrotoxicity

good bioavailability and T1/2

A

Isavuconazole

29
Q

what is flucytosine used for

A

combo therapy for systemic infections:

cryptococcus

30
Q

MOA of flucytosine

A

interferes with protein and nucleic acid synthesis

31
Q

Flucytosine is distriubted throughout body fluids and tissues including the CNS. It can treat _____

A

cryptococcal meningitis

32
Q

SE of flucytosine

A

bone marrow toxicity - anemia, leukopenia, thrombocytopenia

33
Q

Lipopeptides that inhibit the synthesis of beta glucans of fungal cell walls

high degreee of selectivity towards fungal cells

administered IV

poor penetration of CNS

A

echinocandins (caspofungin, micafungin, anidulafungin)

34
Q

spectrum of activity/tx of echinocandins

A
  • limited to fungi with high levels of beta glucan

invasive infections caused by Candida and Aspergillus - primarily to tx infections that do not respond to other antifungal agents

35
Q

oral systemic drugs for cutaneous and mucocutaneous infections

A

Griseofulvin

Allylamines - terbinafine

36
Q

what drug is used to treat dermatophyte infections (2nd line)

concentrates in keratin precursor cells

A

Griseofulvin

37
Q

drug interaction with griseofulvin

A

increase warfarin metabolism

decrease effectiveness of oral contraceptivs

38
Q

MOA of allylamines

A

inhibit ergosterol syntehsis - inhibit enzyme squalene epoxidase

39
Q

first line drug in the treatment of onychomycosis

keratophilic

A

oral terbinafine

40
Q

what is the first TOPICAL triazole used to treat onychomycosis

low affinity for keratin - better penetration of nail bed

minimal systemic absorption

A

Efinaconazole

41
Q

what are the topical antifungals

A

Polyenes - nystatin

Azoles - clotrimazole, miconazole

Allylamines - terbinafine, naftifine

42
Q

polyene antifungal drug related to amphotericin B that is only used topically

active against most species of Candida

most commonly used in local infections - oropharyngeal and vaginal candidiasis

A

Nystatin

43
Q

two most commonly used topical azoles (used for vulvovaginal candidiasis and dermatophytes infections)

oral lozneges are available for oral thrush

A

clotrimazole and miconazole

44
Q

Drug of choice for asperigillosis

A

Voriconazole

alternative: posaconazole, amphotericin B, echinocandin

45
Q

drug of choice to mild/moderate blastomycosis

A

intraconazole

alternative: fluconazole

46
Q

drug of choice for moderate to severe blastomycosis

A

amphotericin followed by itraconazole

47
Q

drug of choice for vaginal candidiassi

A
  • intravaginal azole: clotrimazole, miconazole

or

intravaginal nystatin

or

fluconazole (oral)

48
Q

drug of choice for oropharyngeal candidiasis

A

clotrinmazole or miconazole lozenges

nystatin

fluconazole

49
Q

drug of choice for esophageal candidiasis

A

fluconazole

50
Q

drug of choice for invasive candidiasis or blood stream

A

fluconazole

echinocandin

51
Q

drug of choice for coccidiomycosis

A

fluconazole or itraconazole

Pharm exam 4 (15 decks)

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