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Pharm Exam 4 > AntiFungal Drugs > Flashcards

AntiFungal Drugs Flashcards

1
Q

Systemic dimorphic fungi list

A
  • Histoplasma capsulatum
  • Blastomyces dermatiditis
  • Coccidioides immitis
  • Sporothrix schenckii (cutaneous only)
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2
Q

Opportunistic fungi list

A

1) candida - esophagitus, vagina, thrush
2) aspergillus - mold - lung infections - fungus balls, burn patients
3) cryptococcus - India ink stain - CNS(fungal meningitis) and repiratory

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3
Q

Cutaneous/Subcutaneous fungi list:

A

1) sporothrix schenckii
2) dermatophytes (trichophyton, epidermophyton, microsporum)
- ringworm
- athletes foot
- onychmycosis

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4
Q

Sporothrix schenckii - how to get?

A

Poking yourself with rose bush thorns

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5
Q

Unique targets on fungi:

A

1) fungal cell membrane - ergosterol and ergosterol synthesis (no cholesterol like us)
2) fungal cell wall - glucans

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6
Q

Shared targets with fungi:

A

1) DNA/RNA synthesis

2) cell division

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7
Q

Amphotericin B

-MOA?

A

attacks membrane function - BINDS to ergosterol

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8
Q

Caspofugin

-MOA?

A

cell wall synthesis attacker

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9
Q

5-fluorocytosine

-MOA?

A

nucleic acid synthesis attacker

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10
Q

Fluconazole, itraconazole, voriconazole, naftifine, terbinafine
–>MOA for all?

A

ergosterol synthesis attacker (membrane)

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11
Q

Polyene drug list:

A

amphotericin B

nystatin

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12
Q

Azole drug list:

A 
ketoconazole
fluconazole
itraconazole
voriconazole
posaconazole
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13
Q

Nucleoside analog drug list:

A

flucytosine

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14
Q

Echinocandins drug list:

A

caspofugin
micafugin
anidulafugin

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15
Q

Allylamine drug list:

A

terbinafine

naftifine

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16
Q

Microtubule inhibitor drug list:

A

griseofulvin

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17
Q

Drugs for Systemic infections:

-Administration?

A
  • polyene = amphotericin B
  • Azoles= most
  • flucytosine
  • echinocandins

-oral or IV

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18
Q

Azole used for?

A

oral or IV for systemic infections

topically for cutaneous and mucocutaneous

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19
Q
  • Drug with broadest spectrum of activity of all antifungals?
  • Issue with drug?
A

-amphotericin B

TOxic! replaced by azole and echinocandin compounds

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20
Q

Amphotericin B

MOA?

A
  • binds to ergosterol in fungal cell membrane = forms Amp B containing pores = alters membrane permeability = leaky membrane
  • binds more to ergosterol than cholesterol
  • FUNGICIDAL
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21
Q

Fungi you can use amphotericin B for?

A
  • candida
  • cryptococcus
  • aspergillus
  • histoplasma
  • coccidioides
  • blastomyces
  • sporothrix
  • mucormycoses
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22
Q

Mechanism of resistance to Amphotericin B?

A

-membrane concentration decreased –> sterol target is modified

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23
Q

Pharmacology of Amp B

  • solubility?
  • distribution?
A
  • poor in water–> given IV complexed to bile

- distributed everywhere but poor CNS penetration (need intrathecal)

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24
Q

Amp B

  • toxicities?
  • how to make less toxic?
A
  • Nephrotox = Most serious long term - decreases renal perfusion
  • other infusion related reactions

-liposomal packaged amp B

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25
Q

Systemic use Azoles:

A

TRIAZOLES:

  • fluconazole
  • itraconazole
  • voriconazole
  • posaconazole
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26
Q

Azoles used more topically/ not systemic:

A

IMIDAZOLES:

  • ketoconazole
  • miconazole (topical)
  • clotrimazole (topical)
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27
Q

Azoles

MOA?

A

-INH ergosterol synthesis

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28
Q

Azoles vs Amp B MOA?

A
  • Azole = inh ergosterol synthesis

- Amp B = binds ergosterol

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29
Q

Azoles can treat which fungi?

A

1) pathogenic yeast
- candida
- cryptococcus
2) systemic mycoses
- histoplasmosis
- blastomycosis
- coccidioidomycoses
3) dermatophytes
- onychomycoses

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30
Q

Resistance to azoles - mechanisms:

A
  • efflux pumps
  • mutations in target enzyme
  • decreased ergosterol content in cell membrane
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31
Q

Azoles

-Adverse reaction:

A
  • relatively non-toxic
  • minor GI
  • interact with -450s
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32
Q

One of the first azoles out on market but a lot of liver inhibition (p450s) compared to newer azoles - which azole?

A

ketoconazole

33
Q

Which azole has highest therapeutic index (least liver interaction) and is pretty much used all the time for fungi?

A

fluconazole

34
Q

Fluconizole is agent of choice for treating which bugs?

A

First line:

  • candida
  • cryptococcus
  • coccidiomycoses

Second line:

  • histoplasmosis
  • blastomycosis
  • sporotrichosis
35
Q

Pharmacology of fluconizole:

  • solubility?
  • distribution?
  • absorpion?
A
  • very water soluble
  • distributes everywhere AND CNS TOO
  • 90% absorbed from GI
36
Q

Itraconazole

  • why use this anti-fungal?
  • why is it worse than Fluconizole?
A
  • broader spectrum than fluconizole but poorer pharmacology and therapeutic index
  • lipophillic = not water sol
  • low pH needed for absorption (PPIs or H2 blockers not good = antiacid)
  • no CNS penetration
37
Q

Rifampin (anti-TB drug) interacts with which anti-fungal and lowers concentration to below therapeutic levels?

A

itraconazole

38
Q

Itraconazole used for which fungal infections?

A
  • blastomycosis
  • coccidiomycoses
  • histoplasmosis
  • sporotrichosis
  • dermatophyte (onychomycosis)
39
Q

*Old and new tx of choice for aspergillus? Why?

A
  • was fluconazole

- now is voriconazole –> much lower toxicity

40
Q

Voriconazole

  • liver complications?
  • adverse effects?
A
  • like other azoles it reacts with p450s = drug interactions are a concern
  • visual disturbances
  • blurred vision
  • photophobia
  • hallucinations
  • liver enzyme abormalities*
  • rash*
41
Q

**Which azole can be used to treat cryptococcus, candida, mucormycoses and aspergillus?

A

posaconazole

42
Q

Newest antifungal on market with good results- low tox, broad spectrum, distribution good…:

A

posaconazole

43
Q

Flucytosine can be used to treat in combo therapy?

A

cryptococcus* (meningitis)*

some candida

44
Q

Flucytosine

  • MOA?
  • pharm stuff:
A
  • Active form 5-FU and derivatives are incorporated into RNA or DNA disrupting protein/DNA synthesis
  • oral
  • water sol
  • rapid and well distributed+CNS!
45
Q

Key drug for tx of cryptococcal infections?

A

-flucytosine

46
Q

How is resistance to flucytosine developed?

A

altered metabolismof flucytosine

47
Q

Flucytosine adverse reactions:

A

-bone marrow suppression = anemia, leukopenia, thrombocytopenia

48
Q

Echinocandins

  • molecular level-type of drug?
  • MOA?
  • 3 main drugs in this category?
A
  • lipopeptide
  • Inh synthesis of Beta-glucan (fungal cell wall)
  • caspofungin
  • micafungin
  • anidulafungin
49
Q

Drug name ends in fungin - what class of drug?

A

echinocandins - beta-glucan synthesis inh = no cell wall

50
Q

Echinocandins good for what kind of fungi?

A

only those that have a lot of beta glucan in cell wall = membrane instability with drug

51
Q
  • Primary use for echinocandins?

- why not used often?

A
  • invasive infections -candida and aspergillus

- so effin expensive $$$

52
Q

Echinocandins

  • route?
  • distribution? CNS?
A
  • IV

- wide distribution but not CNS

53
Q

echinocandins

-Adverse stuff?

A

-we dont have cell walls so not many side effects but YES drug interactions

54
Q

Griseofulvin

  • MOA?
  • where does it concentrate?
  • dosing?
A
  • Microtubule inhibitor drug (mitosis inh)
  • concentrates in keratin precursor cells = bound to keratin
  • daily for weeks=skin and hair inf
  • daily for months for nail inf
55
Q

Which drug is a microcrystaline drug = susspension of drug that patient takes with fatty meal?

A

griseofulvin

56
Q

scalp or hair fungal infection give which drug?

A

griseofulvin

57
Q

Which drug interacts with warfarin and also dec effectivenes of oral contraceptives

A

-griseofulvin

58
Q

Allylamines

-MOA?

A
  • inhibitors of ergosterol synthesis (like azoles)

- inh squalene epoxidase enzyme = damaged cell membrane

59
Q

First line drug for onychomycosis?

-MOA?

A
  • terbinafine - concentrates in keratin cells

- -ergosterol synthesis -inh squalene epoxidase enzyme = damaged cell membrane

60
Q

Topical antifungals

  • polyenes?
  • MOA?
A

nysatin

  • binds to ergosterol in membrane (like AmpB) and forms pores
  • ONLY TOPICAL - toxic otherwise
61
Q

Topical antifungals

  • azoles?
  • used for?
A

clotrimazole
miconazole
-give for tinea corporis, pedis and cruri
-also good for candida

62
Q

Topical antifungals

-allylamines?

A
  • terbinafine

- naftifine

63
Q
  • some pateint has oral candidasis
  • some patient has vaginal candidiasis?

WHAT drug to give?

A

nystatin!!!

64
Q

Which drug to give for tinea corporis, pedis and cruris?

A

clotrimazole or miconazole (azoles)

-can do terbinafine and naftifine for cruris (jock itch) and corposris (ringworm)

65
Q

patient has oral THRUSH - which drug?***

A

lozenges - azoles - clotrimazole or miconazole

66
Q

Aspergillosis

-drug of choice?

A

voriconazole

67
Q

Mild to moderate blastomycosis

-drug of choice?

A

itraconazole

68
Q

moderate to severe blastomycoses

-drug of choice?

A

-amphotericin B followed by itraconazole

69
Q

Vaginal candidiasis

-drug of choice?

A
  • intravag azole (clotrimazole or miconazole)
  • intravag nystatin
  • oral floconazole
70
Q

Oral candidiasis

-drug of choice?

A
  • clotrimazole or miconazole lozenge
  • nystatin oral suspension
  • fluconazole
71
Q

esophageal candidiasis

-drug of choice?

A

-fluconazole

72
Q

invasive blood stream candidiasis?

A
  • fluconazole

- echinocandin

73
Q

Coccidioidomycoses

-drug of choice?

A
  • fluconazole

- itraconazole

74
Q

cyroptococcosis - normal pt?
-drug of choice?

cryptoccoccosis - HIV patients
-drug of choice?

A
  • amphotericin B +flucytosine followed by fluconazole

- fluconazole

75
Q

Histoplasmosis - normal pt
-drug of choice?

Histoplasmosis - HIV+
-drug of choice?

A
  • amphotericin B and then itraconazole

- itraconazole

76
Q

Mucomycosis

-drug of choice?

A

-amphotericin B

77
Q

Sporotrichosis - cutaneous
–drug of choice?

Sporotrichosis - extracutaneous
-drug of choice?

A
  • itraconazole

- amphotericin then itraconazole

78
Q

Dermatomycosis

-drug of choice?

A
  • topical azole (clotrimazole or miconazole)

- topical terbinafine

79
Q

Onchymycosis

-drug of choice?

A
  • terbinafine (oral)

- itraconizole (oraL)

Pharm Exam 4 (10 decks)

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