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PDAT6 ID > 31/32 - AntiFungals > Flashcards

31/32 - AntiFungals Flashcards

1
Q

What type of fungi?

Yeast w/ Large Capsule

A
  • *Cryptococcus**
  • neoformans*
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2
Q

What type of fungi?

Acute Angle Branching Hyphe

A

ASPERGILLUS

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3
Q

What type of fungi?

Normally in CAPSULE –> burst out

A

COCCIDIODES Immitis
(BURST OUT)
Dimorphic Fungi

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4
Q

What FUNGAL FORM?

UniCellular
single cells / spherical / rigid cell wall

Round/Oval, Smooth + Flat colonies
that reproduce by:
BUDDING

A

Candida** + **Cryptococcus

UniCellular
single cells / spherical / rigid cell wall

Round/Oval, Smooth + Flat colonies
that reproduce by:
BUDDING

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5
Q

What FUNGAL FORM?

Filamentous
Filaments called Hyphae, collectively = Mycelium

Appear:
Fuzzy / Growth through BRANCHING

A

MOLDS

Aspergillus** + **Mucor** + **Fusarium

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6
Q

What FUNGAL FORM?

Exists as YEAST or MOLD
Dependent on environment

Yeast > 37*C

Mold = Environment

A

DIMORPHIC

Blastomyces Dermatitdis

Cocciodiodes (burst)

Histoplasma Capsulatum

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7
Q
  • *Candida Susceptabilities:**
  • *What ANTIFUNGAL** has activity against:

C. Albicans** & **C. Tropicalis

A

ALL ANTIFUNGALS

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8
Q
  • *Candida Susceptabilities:**
  • *What ANTIFUNGAL** has activity against:

C. Parapsilosis

A

All Antifungals:

EXCEPT
ECHINOCANDINS = S-R
Caspofungin / Micafungin / Anidula fungin

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9
Q
  • *Candida Susceptabilities:**
  • *What ANTIFUNGAL** has activity against:

C. Glabrata

A

FLUCYTOSINE** + **EchinoCandins

S-Intermediate = Amphotericin

S-DD-R = Itraconazole

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10
Q
  • *Candida Susceptabilities:**
  • *What ANTIFUNGAL** has activity against:

C. Krusei

A
  • *ESCHINOCANDINS**
  • fungins

Resistant to FLUCONAZOLE

S-DD-R = Itraconazole

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11
Q
  • *Candida Susceptabilities:**
  • *What ANTIFUNGAL** has activity against:

C. Lusitaniae

A

ALL antifungals EXCEPT:
AMPHOTERICIN B
only S-R

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12
Q

Which Antifungal MoA?

Forms aggregates in cell membrane w/ ERGOSTEROL
Leading to:
Pores that cause leakage of cellular contents

A

AMPHOTERICIN B

Liposomal / Lipid-Complex / deoxycholate

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13
Q

Which Antifungal MoA?

BLOCK biosynthesis of ergosterol,
sterol needed for cell-membrane stability
VIA
Fungal CYP450 Inhibition

A

TRIAZOLES
Fluconazole + Voriconazole
Itracanozole + Ketoconazole
Posaconazole + Isavuconazole

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14
Q

Which Antifungal MoA?

DISRUPT function of the (1->) B-D-Glucan Synthase Complex

A

ECHINOCANDINS
Anidula-fungin
Mica-fungin
Caspo-fungin

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15
Q

Which Antifungal MoA?

Disrupts fungal RNA & DNA Syntheis
5FUTP & 5FdUMP

A
  • *FLUCYTOSINE**
  • *5-FC**
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16
Q

Which antifungals require TDM

THERAPEUTIC DRUG MONITORING

A
  • *AZOLES**
  • *Itra**conazole + Voriconozole + Posaconazole
  • except FLUCONAZOLE*

FLUCYTOSINE

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17
Q

What ANTIFUNGALs can be used in
PREGNANCY?

A
  • *AMPHOTERICIN B**
  • *DOC for Invasive Candidiasis** in Pregnancy
  • can’t use AZOLES except…*
  • *Fluconazole 150mg x1 dose**
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18
Q

Which ANTIFUNGALs require

RENAL DOSING?

A

FLUCYTOSINE
Primarily as adjuvent in cryptococcal meningitis

FLUCONAZOLE

Fluconazole = 80% renal elimination
is also why..
GOOD URINARY PENETRATION –> for Urinary Infections

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19
Q

Which ANTIFUNGAL requires
HEPATIC Dose ADJUSTMENT?

A

VORICONAZOLE
Dose adjust ment in Mild-Moderate Liver Dysfunction
CP Class A/B–>std LD –> 50% MD

CASPOfungin
Requires adjustment in Chronic Liver Disease
Tacro + Rifampin

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20
Q

Dosing Considerations

Amphotericin B

A
  • no dose adjustment for renal/hepatic*
  • *NEPHROTIXIC**
  • may reduce if toxicity occurs*
  • *Dosing based on FORMULATION**
  • Liposomal vs Lipid Complex vs Deoxycholate** (lowest dose)*
  • *Total Body Weight**
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21
Q

Amphotericin B

ADR / Drug Interactions / Monitoring

A

LIPID FORMULATIONS = less ADR
vs deoxycholate

NEPHROTIXIC + Electrolyte Wasting Mg/K

Infusion-Related Reactions
3-5 days = fevers / chills / rigors
premedicate w/ hydrocortisone

DIGOXIN –> hypoKalemia

Monitor:
Creatinine / Urine Output / K / Mg / LFT / Ca

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22
Q

Itraconazole

Spectrum

A

Endemic Fungi
most commonly used for HISTOPLASMA CAPSULATUM

  • *S-DD-R** for C. Glbrata & C. Krusei
  • dose dependent susceptibility*

Aspergillus

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23
Q

Itraconazole

Dosing Consideration

A

TDM vis HPLC + Loading Dose

Capsules:

  • *MEAL +/- ACIDIC ENVIRONMENT**
  • do NOT use PPI or H2RA*

Solution:
fine to be fastig

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24
Q

Itraconazole

ADR / DI / Monitoring

A

ADR:

  • Peripheral Neuropathy** ↑LFT *_hypokalemia_
  • *Negative Inotropic Activity**

DI:
CYP3A4 Substrate + Inhibitor
PPI**+**H2RA
CI w/ STATINS (except pravastatin)

Monitoring:
LFT / S/Sx CHF / Rash

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25
Q

Fluconazole

Spectrum

A

RESISTANT to C. KRUSEI

DD-R for C. Glabrata

Cryptococcus (Capsule Yeast)

Endemic Fungi

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26
Q

Fluconazole

Dosing Considerations

A

no TDM

  • *Loading Dose Required**
  • *double dose for C. Glabrata** in Invasive Candidiasis

RENAL DYSFUNCTION DOSAGE ADJUSTMENT
80% renally eliminated

27
Q

Fluconazole

ADR / CI / Monitoring

A

ADR:
Well tolerated - NV - ↑LFT - HA - Reversible Alopecia

CI:
weak inhibitor of CYP450, none

Monitoring:
LFTs / Rash / QT interval in high risk pts

28
Q

Voriconazole

SPECTRUM

A

ASPERGILLUS Spp
DOC

Fusarium** + **Scedosporium

  • not fully susceptable = S-R for*
  • *C. Glabrata** & C. Krusei
29
Q

Voriconazole

Dosing Considerations

A

TDM** + **Loading Dose

DOSE ADJUSTMENT for LIVER DYSFUNCITON
Child Pughs A/B
std LD –> 50% MD

30
Q

Which ANTIFUNGAL has

serious / a lot of ADRs
VISUAL DISTURBANCES
photopsia hallucinations

A

VORICONAZOLE

Need to monitor:
VISUAL FUNCTION
Renal function / Bilirubin / LFT

31
Q

Voriconazole

ADR / CI / Monitoring

A

A LOT OF ADR:
VISUAL DISTURBANCES (photosphisa / hallucinations)
HEPATOTOXICITY
Peripheral Neuropathy
Prolonged QT & TDP (torsades)

DI:
CYP2C19 Metabolism

Monitoring:
↑LFT / Bilirubin / Renal Fxn / Visual Function

32
Q

Posaconazole

SPECTRUM

A

MUCOR
one of the few who have this activity

Aspergillus** + **Endemic Fungi

  • some resistance S-R to:*
  • *C. Glabrata + C. Krusei**
33
Q

Posaconazole

Dosing Considerations

A

TDM** + **Loading Dose

SUSPENSION:
ACIDIC ENVIRONMENT**+**HIGH FAT MEAL
no dose adjustments, no longer used

  • *DELAYED RELEASE TABLET**
  • *IMPROVED ABSORPTION > Suspension**
34
Q

Posaconazole

ADR / CI / Monitoring

A

ADR:
Similar to Fluconazole

DI:

  • not CYP metabolism but* affected by : Rifabutin / Phenytoin
  • Inhibits CYP3A4* / ↑Cyclosporin

Monitoring:
PO Intake / Diarrhea
LFTs / Bilirubin / K / Mg / Ca

35
Q

Isavuconazole

SPECTRUM

A

Indicated for:
Invasive ASPERGILLOSIS** + **MUCORmycosis

  • some resistance S-R to:*
  • *C. Glabrata + C. Krusei**

Cryptococcus + Scedosporium + Endemics

36
Q

Isavuconazole

Dosing Considerations

A

TDM** + **PRODRUG

Requires LOADING DOSE

37
Q

Isavuconazole

ADR / CI / Monitoring

A

ADR:

  • less ADR* vs Voriconazole
  • *Nusea / Hepatotoxicity** / CNS = AMS + Seizure

DI:

  • *Inhibitor + Metabolized by CYP3A4**
  • *Mild P-GP inhibitor**

Monitoring:
LFTs / K / Mg

38
Q

Echinocandins -fungins

Spectrum

A

FungiCIDAL

Primary role:

  • *CANDIDA** (including Azole-Resistants)
  • except for C. Parapsilosis (S-R)*

Aspergillus

less ectivity vs Fusarium / Cryptococcus

39
Q

EchinoCandins

Dosing Considerations

A

IV ONLY

  • *CASPO + ANIDULA** = Require LOADING DOSE
  • MICAfungin does NOT need LD*

CASPOFUNGIN needs HEPATIC adjustment
Child-Pughs 70mg LD –> 35mg/day (instead of 50)

40
Q

Which Echinocandin(s) require

DOSE ADJUSTMENT in CHRONIC LIVER DISEASE?

A

CASPOfungin
based on Child-Pughs
70mg LD –> 35 mg MD (vs 50mg MD)

41
Q

Which Echinocandin(s) require

LOADING DOSE?

A

CASPOfungin** + **ANIDUAfungin
loading dose needed

  • micafungin*
  • does NOT need LOADING DOSE*
42
Q

Which Echinocandin has a

DRUG INTERATION?
and with what?

A

CASPOfungin
also requires hepatic dose adjustment

↓Tacrolimus Concentrations

Rifampin –> ↓Caspo Concentration via OATP1B1
requires:
↑Caspo Dose to 70mg QD w/ Rifampin and others:
phenytoin / carbamazepime / efavirenz / nevirapine

43
Q

EchinoCandins

ADR / Monitoring

A

no drug interactions
EXCEPT for CASPOfungin = rifampin

↑LFTs

Monitor:
CBC & LFT

44
Q

Flucytosine = 5-FC

SPECTRUM

A

Primarily as:

  • *ADJUVENT_ in _CRYPTOCOCCAL MENINGITIS**
  • not used on its own*
  • *Candida Activity**
  • except C. Krusei*
45
Q

Flucytosine 5-FC

Dosing Consideration

A

100-150 mg/kg/day IV/PO in four divided doses

RENAL DOSING ADJUSTMENT

requires:
TDM

+ not given as monotherapy

46
Q

Flucytosine 5-FC

ADR / CI / MOnitoring

A

ADR:
Rash / Diarrhea / LIVER toxicity
HEMATOLOGIC TOXICITY

Monitor:
CBC / Creatine / urine
LFT / Serum Levels

47
Q

Which antifungal is

CONTRAINDICATED with STATINS?

A

ITRACONAZOLE
CI w/ statins except PRAVAstatin

Also avoid:
PPI + H2RA

CYP3A4 Substrate + Inhibitor

48
Q

Risk Factors for

Candidiasis

A

Use of:
Broad Spectrum ABx

Central Venous Catheters** + **TPN

Dialysis / Neutropenia / IMS

Recent ItraAbdominal SURGERY

Prosthetic Devices

Colonization @multiple sites (urine)

49
Q

Candidiasis

Empiric Treatment + Duration

A

ECHINOCANDINS
Especially if patient is:
Critically Ill / RECENT AZOLE / Neutropenia

2 WEEKS
starting from 1st negative blood culture or SOURCE CONTROL

Can step down from Echinocandins:
Fluconazole 800mg LD –> 400mg QD

50
Q

Which Fungal Infection?

Commonly from:

  • *CATHETER** or GI source
  • remove central venous catheter if possible*

Fundoscopic Exam –> EYE

Mouth = Thursh

Vulvovaginal

Urine

A

CANDIDIASIS
Candida = Budding ROUND Yeast

If in BLOOD = CANDIDEMIA
treat ASAP <12 hours = best mortality

51
Q

Which Fungal Infection?

Universal Exposure –> INHALATION

Presents as:
Invasive Pulmonary / Bronchopulmonary / CNS

Risk Factors:
Prolonged Neutropenia ANC < 100
Hematologic Malignancy / Steroid Use

AML / BMT / SOT (lung esp)

A
  • *ASPERGILLOSIS**
  • *Acute Angle Septate BRANCHING**

Common Species:
A. FUMIGATUS > A. Flavus > A. Niger

52
Q

Aspergillosis

DIAGNOSIS

A

DIFFICULT to Diagnose

  • *Biopsy = Definitive**
  • but difficult to do and INVASIVE*

GALACTOMANNAN = Specific
in high risk population

Beta-D Glucan = NONspecific

  • *CT IMAGING**
  • *HALO SIGN** - nodules / wedge shaped legions
53
Q

Aspergillosis

TREATMENT

A

VORICONAZOLE
1st line

Isavuconazole = 2nd line

Other agents w/ Activity:
Amphotericin / Echinocandins

54
Q

Which Fungal Infection?

Mainly affects:
Immunocompromised / AIDS patients

Presents as:
Meningitis / Pneumonia

Culture shows:
CAPSULE

A
  • *CRYPTOCOCCAL DISEASE**
  • *CAPSULE one**

Diagnosed with:
Cryptococcal Antigen Culture

55
Q

Which Fungal Infection?

Commonly presents as:
Pulmonary Disease

IMS patients –> disseminated histoplasmosis in GI tract

Endemic / Dimorphic –> Certain Areas
Can be found in SOIL / Avian Droppings

Can disseminate anywhere:
CNS / Skin / Bone

A

DIMORPHIC FUNGI

ENDEMIC DISEASE

Specific Fungus depends on GEOGRAPHIC AREA

56
Q

CRYPTOCOCCAL DISEASE
CAPSULE one

Treatment

A

Meningitis Treatment:
AMPHOTERICIN B** + **FLUCYTOSINE for 2 Weeks
then….
Fluconazole 400mg QD –> 8 Weeks
then
Fluconazole 200mg/day –> > 1 YEAR

  • *IRIS CONSIDERATION**
  • -> DEFER ART for 5 weeks POST TREATMENT
57
Q

Dimorphic Fungi (Endemics)

INDUCTION TREATMENT
for
Severe Disease

A

for SEVERE disease:
AMPHOTERICIN B
vvv
May step down / consolidate therapy with triazole

58
Q

Dimorphic Fungi (Endemics)

Non-Severe Treatment
Histoplasma Capsulatum

A

ITRACONAZOLE

59
Q

Dimorphic Fungi (Endemics)

Non-Severe Treatment
Coccidioides Spp

A

ITRACONAZOLE

60
Q

Dimorphic Fungi (Endemics)

Non-Severe Treatment
Blastomyces Dermatitidis

A

Fluconazole = CNS

Voriconazole** or **Itraconazole

61
Q

Which Fungal Infection?

Commonly presents as:
Invasive Sinus** / **Rhinocerebral disease
w/ Rapid Tissue necrosis

  • *Facial Pain / Unilateral HA / Drainage / Tissue sWELLING**
  • pulmonary / cutaneous / disseminated = LESS common*
A
  • *ZYGOMYCOSIS**
  • *Mucor / Mucormycosis / Rhizopus**

Found in:
Environment / DECAYING matter

62
Q
  • *ZYGOMYCOSIS**
  • *Mucor / Mucormycosis / Rhizopus**

RISK FACTORS

A

Found in:
Environment / DECAYING matter

Long-Standing IMS state
or
Uncontrolled DIABETES

TRAUMA / DEFEROXAMINE

63
Q

ZYGOMYCOSIS
Mucor / Mucormycosis / Rhizopus

TREATMENT

A

Primary Treatment:
SURGERY** + **restoration of immune system

Other Treatment:
Amphothericin B** or **Posaconazole** or **Isavuconazole
may combine 1 of above w/
Echinocandin

HIGH MORBIDITY / MORTALITY TREAT RIGHT AWAY = SURGERY

PDAT6 ID (31 decks)

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