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PHRM 865 > Exam 4 - Fungal (Kays) > Flashcards

Exam 4 - Fungal (Kays) Flashcards

1
Q

what are the most common fungal pathogens?

A 
Candida species
Aspergillus species
Cryptococcos neoformans
Zygomycetes 
Endemic Fungi (related to your region)
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2
Q

What are types of Zygomycetes

A

Rhizopus
Absidia
Mucor

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3
Q

what are types of endemic fungi

A

histoplasma capsulatum
blastomyces species
coccidioides immitis

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4
Q

Is it a yeast or a mold?

Candidia

A

yeast

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5
Q

Is it a yeast or a mold?

Aspergillus

A

mold

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6
Q

Is it a yeast or a mold?

cryptococcus

A

yeast

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7
Q

Which fungal pathogen?
is enacpsulated and
primarily affects CNS and respiratory tract

A

cryptococcus neoformans

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8
Q

Which fungal pathogen?

risk factor includes penetrating injuries from natural disasters?

A

Zygomycetes

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9
Q

Which fungal pathogen?

is common in midwestern states/happens from exposure to bat guano/cave exploration/from contrstruction

A

histoplasma capsulatum

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10
Q

Which fungal pathogen?

common in southwestern US

A

coccidiodies

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11
Q

what is the most common species of Candidia?

A

C. Albicans

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12
Q

what is the most drug resistant species of Candidia?

A

C. Auris

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13
Q

Candida species:

increased mortality if empiric antifungal therapy doesn’t happen within ______

A

12 hours

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14
Q

Candida species:

what are some risk factors for invasive candidiasis

A 
prolonged ICU stay
central venous catheters
prolonged therapy with broad spec abx
receive parenteral nutrition
recent surgery (esp abdominal)
hemodialysis
diabetes...
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15
Q

PD parameter for Amphotericin B?

A

Peak/ MIC

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16
Q

PK of Amphotericin?
CSF?
Renal / Hepatic?
PO or IV?

A

poor CSF penetration
no adjustment for Renal or hepatic needed
bad PO absorption – must do IV

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17
Q

Dosing Notes about Amphotericin?

A

do a TEST DOSE
can do bigger doses if use lipid formulations
Infused over 4- 6 hours!!

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18
Q

ADEs of Amphotericin?

A

Infusion related (fever, chills, arhtralgias, myalgias, N/V) & thrombophlebitis

Nephrotoxicity
Hypo kalemia and magnesemia
Bicarb wasting
anemia

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19
Q

How to manage Amphotericin infusion related rxns?

A

pre-treat - APAP, antihistamines, anti-nausea meds
add hydrocortisone to infusion
TOLERANCE WILL DEVELOP

give slower rxn to help with thrombophlebitis

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20
Q

MOA of flucytosine

A

5-FC enters fungal cell — gets made into 5-FU and gets into fungal RNA and stops protein synthesis

or inhibits thymidylate synthetase and interferes with DNA synthesis

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21
Q

Flucytosine is used mainly for what fungal pathogen?

A

Cryptococcus

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22
Q

PK of Flucytosine?
CSF?
Renal/hepatic?
PO or IV?

A

great CSF
renal adjsut!!/excreted in urine (HD and PD pull it out)
great PO absorption – oral!

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23
Q

drug interactions of amphotericin?

A 
nephrotoxic agents (bc more nephrotoxicity)
Digoxin/Skeletal muscle relaxants -- hypokalemia risk
\+ Flucytosine = better therapeutic effect but toxicityyyy
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24
Q

ADE of flucytosine?

A

Bone marrow suppression

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25
Q

Normal dose for Flucytosine

A

100 - 150 mg/kg day

and DIVIDED in 4 doses

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26
Q

Monitoring for Flucytosine

A

CBC/Platelets (because marrow suppression)

SCr/BUN (because renal adjsut)

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27
Q

Ketoconazole MOA?

A

inhibits egosterol synthesis
via inhibiting lanosterol 14 a demethylase
also membrane gets wack without egosterol = leakage

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28
Q

Ketoconazole:

-cidal or - static

A

static

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29
Q

PK of Ketoconazole:
CSF?
Renal/Hepatic adjustments?
PO or IV?

A

negligible CSF
metabolized by liver extensively
PO absorption is related to gastric pH

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30
Q

Ketoconazole:

Oral absorption: related to gastric pH how?

A 
inversely!
lower pH (more acidic) = more absorption
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31
Q

ADEs of Ketoconazole?

A

Hepatoxicity

Endocrine: Menstural irregularities, Hair loss, libido/sperm issues, and Gynecomastia

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32
Q

Drug interactions of Ketoconazole?

A

It is a POTENT CYP3A4 inhibitor:
therefore — anticoag, rifampin, cyclosporine/tacrolimus/sirolimus, phenytoin
ALSO
anything that decreases stomach acid (H2RA, PPIs antacids)

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33
Q

PK of Itraconazole:
CSF?
Renal/hepatic?
PO or IV?

A 
poor CSF
liver metab (NO renal adjust)
PO dependent on acidity!! take with cola for capsules (oral solution - acidity doesnt matter)
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34
Q

Itraconazole ADEs

A

Hepatoxicity
CHF – boxed warning
Avoid (CONTRAINDICATED) in pregnant/nursing women
peripheral neuropathy

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35
Q

Boxed warning for itraconazole?

A

CHF!! (present or history) negative inotropic effect

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36
Q

Drug interactions for Itraconazole?

A

PPIs/H2RAs/Antacids - because acidity needed

CYP3A4 interactions

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37
Q

PK of Fluconazole:
CSF?
Renal/Hepatic?
PO or IV?

A

great CSF
needs renal adjustment
PO absorption is great

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38
Q

ADEs of Fluconazole

A

QT prolongation

Elevation in hepatic transaminase

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39
Q

Voriconazole:

Does it cover Aspergillus, Mucor, or both?

A

Aspergillus - NO MUCOR

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40
Q

PK of Voriconazole:
CSF?
Renal/Hepatic?
PO or IV?

A

IDK about CSF…
renal adjust when IV!!!! (not oral)
great PO availability

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41
Q

Oral Voriconazole tips?

A

acid reducers do NOT matter for this

this is best 1 hour BEFORE OR AFTER a meal

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42
Q

ADEs of Voriconazole

A

Visual disturbances
Elevated LFTs
Phototoxic skin rxns

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43
Q

Adjust Voriconazole for renal elimination when?

A

Adjust when IV and CrCl < 50 mL/min

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44
Q

PK of Posaconazole?
CSF?
Renally or Hepatic?
PO or IV

A

idk about CSF…
Renally adjustment needed

PO – needs acidic to be absorbed
IV - RENAL ADJUST

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45
Q

when do you avoid Posaconazole and Voriconazole due to renal issues

A

when IV formulation and CrCl is < 50 mL/min

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46
Q

Drug interactions for Posaconazole?

A

CYP 4 dayz

and acid reducers!

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47
Q

ADes of Posaconazole

A

Elevated LFTs/billirubin
hypokalemia
Rash

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48
Q

PK of Isavuconazole
PO or IV?
Renal/hepatic?

A

PO has great bioavail - so PO or IV is fine
NO renal adjustment needed
NO hepatic adjustment needed

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49
Q

Why do some IV azoles need to be avoided when CrCl is < 50 mL/min

A

something to do with their formulation having cyclodextrin??

Isavuconazole does not have cyclodextrin = does not need renal adjustment

50
Q

ADEs of Isavuconazole

A

increased LFTs
infusion related reaction
*NO QT PROLONGATION actually SHORTENS QT

51
Q

what is an abnormal Qt interval?

A

male over 450 ms

females over 470 ms

52
Q

Contraindications for Isavuconazole?

A

coadministration of any strong CYP3A4 inhibitors or inducers

patients with familial SHORT qt syndrome (this drug will shorten QT)

53
Q

Examples of strong CYP3A4 inhibitors:

A

Ketoconazole

high dose ritonavir

54
Q

Examples of strong CYP3A4 inducers

A

CBZ
rifampin
St. Johns Wort
Long acting barbiturates

55
Q

MOA of Caspofungin

A

glucan synthesis inhibitor = prevents from fungal cell wall from being made

56
Q

The echinocandin drugs have what suffix?

A

-fungin

57
Q

spectrum of echinocandin?

A

Candida and aspergillus

58
Q

Azole antifungals affect cell ______

Echinocandins affect cell ______

A

Azole: affect cell membrane
Echinocandins: cell wall

59
Q

which echinocandin needs to be dose reduced with hepatic dysfunction

A

caspofungin

60
Q

Echinocandins:

PO or IV?

A

IV!!

very poor bioavailability

61
Q

VVC stands for?

A

vulvovaginal candidiasis

62
Q

Complicated or uncomplicated VVC?

sporadic infection that is susceptible to all forms of antifungal therapy regardless of treatment duration

A

uncomplicated

63
Q

Complicated or uncomplicated VVC?

Recurrent VVC

A

complicated

64
Q

Complicated or uncomplicated VVC?

Severe disease

A

complicated

65
Q

Complicated or uncomplicated VVC?

Non-candida albicans infection

A

complicated

66
Q

Complicated or uncomplicated VVC?

Candida albicans infection

A

uncomplicated

67
Q

Complicated or uncomplicated VVC?

diabetes/immunocomproised/pregnancy

A

complicated

68
Q

VVC:

Candida species - mono, di, or tri morphic

A

di

69
Q 
patient education for VVC?
Avoid \_\_\_\_\_\_\_\_ to prevent worsening irritation
Keep genital area \_\_\_\_\_\_\_\_\_
\_\_\_\_\_\_ to soothe the skin
\_\_\_\_\_\_\_\_ not recommended
A

avoid harsh soaps
keep it clean and dry
cool baths to soothe
do not douche

70
Q

Pharm Treatment of VVC:

Topical preparations can decrease efficacy of what?

A

latex condoms and diaphragms

71
Q

Pharm Treatment of VVC:

Oral or Topical treatment is better?

A

Equally therapeutic

72
Q

Pharm Treatment of VVC:

Treat for how long if uncomplicated?

A

can be 1 day.. (1 dose fluconazole)

or like 3 - 7 for various topical treatments

73
Q

Pharm Treatment of VVC:

Treat how long if complicated?

A

10 - 14 days!

do this if uncontrolled diabetes or immunocompromised

74
Q

what does OPC stand for and what is it

A

oropharyngeal candidiasis aka THRUSH

candida infection of the oral mucosa

75
Q

what does EC stand for and what is it

A

esophageal candidiasis

esophagus infection from candida

76
Q

what is the primary line of defense against OPC and EC

A

cell mediated immunity (CD4 T cells)

77
Q

LOCAL risk factors for OPC and EC?

A 
steroids/abx
dentures
xerostomia due to drugs, chemo, radiotherapy to head/neck, and BMT(?)
smoking
any disruption to oral mucosa
78
Q

patients with ______ have had much less incidence of OPC and EC due to great drug development

A

HIV

HAART is savin’ them

79
Q

SYSTEMIC risk factors for OPC and EC?

A 
Drugs (cytotoxic, steroids, immunosuppressants after organ transplant)
Neonates or elderly
HIV infection/AIDS
diabetes
malignancy
nutritional deficiencies
80
Q

OPC or EC:

which one is more severe

A

EC

81
Q

OPC or EC:

which one may have a fever more than the other

A

EC

82
Q

OPC Treatment:

Treat for how long?

A

7 - 14 days

83
Q

OPC Treatment:

If mild infection – treat how?

A

TOPICALLY
with clotrimazole troches or nystatin susp
or miconazole buccal tab

84
Q

OPC Treatment:
If pt is refractory, cannot tolerate topical agents, have moderate - severe disease, or high risk for disseminated systemic disease (aka neutropenic) — treat how?

A

do SYSTEMIC
Fluconazole!!
Itraconazole
or Posaconazole

85
Q

OPC Treatment:

If fluconazole refractory – treat how?

A

treat for 14 DAYS
kinda try any antifungal but itraconazole is good

(even try amphotericin…)

86
Q

EC Treatment:

Treat for how long?

A

14 - 21 days?

87
Q

EC Treatment:
Topical treatment when?
Systemic treatment when?

A

NEVER topical for EC

do SYSTEMIC!!

88
Q

EC Treatment:

Treatment options?

A

Fluconazole…
itraconazole…
kinda whatever just do SYSTEMIC

89
Q

EC Treatment:

If fluconazole refreactory – treat how?

A

treat for 21 - 28 days

itraconazole and like every other antifungal option…

90
Q

Risk factors for fungal skin, hair, and nail infections?

A

prolonged exposure to sweaty clothes
failure to bathe regularly
lots of skinfolds
sedentary/confined to bed

91
Q

how to treat tinea capitis

A

oral therapy — terbinafine daily 4 - 8 weeks (clean combs/brushes)

92
Q

How to treat tinea unguium

A 
aka onychomycosis
ORAL therapy
terbinafine: 6 - 12 wks
 or 
itraconazole 8 - 12 wks
or
fluconazole: 6 - 12 mos
(toes need treated longer)
93
Q

what are the different types of histoplasmosis

A

acute pulmonary
chronic pulmonary
disseminated
HIV infected pts

94
Q

Acute Pulmonary Histoplasmosis treatment:

mIld-mod disease with sxs > 4 wks

A

itraconazole 6 - 12 weeks

95
Q

Acute Pulmonary Histoplasmosis treatment:

if mod - severe disease?

A

amphotericin x 1 - 2 weeks THEN itraconazole

also medrol for first 1 - 2 weeks

96
Q

Disseminated Histoplasmosis treatment:

if mod-severe disease?

A

amphotericin x 1 - 2 weeks then itraconazole for 12 months

97
Q

Disseminated Histoplasmosis treatment:

if less severe disease?

A

itraconazole x 12 months

98
Q

if C. glabrata strain — what drug(s) are preferred?

A

echinocandin

99
Q

if C. parapsilosis strain — what drug(s) are preferred?

A

fluconazole or lipid amphotericin

100
Q

if C. krusei strain — what drug(s) are preferred?

A

enchinocandin, lipid amphotericin, or vori

101
Q

what antifungals cover mucor?

A

amphotericin
posaconazole
isavuconazole

102
Q

what antifungal is the DOC for histoplasma

A

itraconazole

103
Q

what antifungal is DOC for aspergillus

A

voriconazole

104
Q

what fungi do echinocandins cover

A

candida and aspergillus

105
Q

what fungi does 5-FC cover?

A

candida and cryptococcus

106
Q

what fungi does ketoconazole cover?

A

candida ALBICANS and cryptococcus and histo

107
Q

what two antifungal drugs cover everything but mucor

“everything” = candida, aspergillus, cryptococcus, histo, blasto, cocci

A

itraconazole and voriconazole

108
Q

what does isavuconazole cover?

A

aspergillus
mucor
rhizopus

109
Q

if we find candida in respiratory tract — what do we do?

A

nothing probably — its usually colonization/ candida does not cause pneumonia

110
Q

if we find candida in the urine what do we do?

A

if asymptomatic and NOT high risk for dissemination — let it goooo

111
Q

who are high risk pts for dissemination form candida UTI?

A

low birth weight infants
pts undergoing urologic procedure
neutropenic patients

112
Q

which fungus is uncommon in HIV infected patients

A

aspergillus

113
Q

galactomannan is a cell wall polysaccharide that is specific to the _________ fungus species and is detectable in serum/other body fluids

A

aspergillus

114
Q

________ is the most important predisposing factor to the development of invasive aspergillosis

A 
prolonged neutropenia
(NOT HIV infection!)
115
Q

DOC for invasive pulmonary aspergillosis

A

voriconazole

116
Q

main drug to use for prophylaxis of aspergillosis

A

posaconazole

117
Q

who would get aspergillosis prophylaxis

A

pts with neutropenia risk (cancer patients and bone marrow transplant pts)

118
Q

which antifungal has a saturable metabolism/pk is NOT linear

A

voriconzaole

119
Q

which antifungal agents need renal adjustment

A

flucytosine and fluconazole

voriconazole IV and posaconazole IV need to be avoided due to cyclodextrin build up in renal dysfunction

120
Q

which antifungal agents need an acidic gastric environment to get absorbed

A

ketoconazole
itraconazole CAPSULE
posaconazole

121
Q

what agents have cyclodextrin in them

A

IV voriconazole
and
IV posaconazole

122
Q

what drugs used for cyptococcus infection?

A

amphotericin AND 5-FC

PHRM 865 (59 decks)

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