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PDAT6 ID > 31/32 - AntiFungals > Flashcards

31/32 - AntiFungals Flashcards

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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
**_Fluconazole_** **Spectrum**
***_RESISTANT to C. KRUSEI_*** **DD-R** for **C. Glabrata** **Cryptococcus** (Capsule Yeast) **Endemic Fungi**
26
**_Fluconazole_** **Dosing Considerations**
***_no TDM_*** * *_Loading Dose Required_** * *double dose for C. Glabrata** in **Invasive Candidiasis** **_RENAL DYSFUNCTION DOSAGE ADJUSTMENT_** 80% renally eliminated
27
**_Fluconazole_** **ADR / CI / Monitoring**
ADR: Well tolerated - **NV** - ↑**LFT** - **HA** - **Reversible Alopecia** CI: ***weak inhibitor of CYP450, none*** Monitoring: **LFTs / Rash / QT interval in high risk pts**
28
**_Voriconazole_** **SPECTRUM**
**_ASPERGILLUS Spp_** DOC **_Fusarium**_ + _**Scedosporium_** * _not fully susceptable = S-R for_* * *C. Glabrata** & **C. Krusei**
29
**_Voriconazole_** **Dosing Considerations**
**_TDM**_ + _**Loading Dose_** **_DOSE ADJUSTMENT for LIVER DYSFUNCITON_** Child Pughs A/B std LD --\> 50% MD
30
**Which ANTIFUNGAL has** **serious / a lot of ADRs _VISUAL DISTURBANCES_** **photopsia hallucinations**
**_VORICONAZOLE_** Need to monitor: **VISUAL FUNCTION Renal function / Bilirubin / LFT**
31
**_Voriconazole_** **ADR / CI / Monitoring**
_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
**_Posaconazole_** **SPECTRUM**
**_MUCOR_** one of the few who have this activity **_Aspergillus**_ + _**Endemic Fungi_** * _some resistance S-R to:_* * *C. Glabrata + C. Krusei**
33
**_Posaconazole_** **Dosing Considerations**
**_TDM**_ + _**Loading Dose_** **SUSPENSION: _ACIDIC ENVIRONMENT**_+_**HIGH FAT MEAL_** *no dose adjustments, no longer used* * *_DELAYED RELEASE TABLET_** * *IMPROVED ABSORPTION \> Suspension**
34
**_Posaconazole_** **ADR / CI / Monitoring**
_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
**_Isavuconazole_** **SPECTRUM**
Indicated for: **_Invasive ASPERGILLOSIS**_ + _**MUCORmycosis_** * _some resistance S-R to:_* * *C. Glabrata + C. Krusei** **Cryptococcus** + **Scedosporium + Endemics**
36
**_Isavuconazole_** **Dosing Considerations**
**_TDM**_ + _**PRODRUG_** ## Footnote **Requires LOADING DOSE**
37
**_Isavuconazole_** **ADR / CI / Monitoring**
ADR: * **_less ADR_*** **vs Voriconazole** * *Nusea / _Hepatotoxicity_** / **CNS = AMS + Seizure** DI: * *Inhibitor + Metabolized by _CYP3A4_** * *_Mild P-GP inhibitor_** Monitoring: **LFTs / K / Mg**
38
**_Echinocandins_** -fungins ## Footnote **Spectrum**
**_FungiCIDAL_** Primary role: * *_CANDIDA_** (including **Azole-Resistants**) * **except for _C. Parapsilosis_ (S-R)*** **Aspergillus** ***less ectivity vs Fusarium / Cryptococcus***
39
**_EchinoCandins_** **Dosing Considerations**
**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
**Which Echinocandin(s) require** **DOSE ADJUSTMENT in CHRONIC LIVER DISEASE?**
**_CASPOfungin_** based on Child-Pughs **70mg LD** --\> **35 mg MD** (vs 50mg MD)
41
**Which Echinocandin(s) require** **_LOADING DOSE?_**
**_CASPOfungin**_ + _**ANIDUAfungin_** loading dose needed * **_micafungin_*** * does NOT need LOADING DOSE*
42
**Which Echinocandin has a** **_DRUG INTERATION?_** and with what?
**_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
**_EchinoCandins_** **ADR / Monitoring**
*no drug interactions EXCEPT for CASPOfungin = rifampin* **↑_LFTs_** Monitor: **CBC & LFT**
44
**_Flucytosine_** = **5-FC** ## Footnote **SPECTRUM**
Primarily as: * *_ADJUVENT**_ in _**CRYPTOCOCCAL MENINGITIS_** * not used on its own* * *Candida Activity** * except **C. Krusei***
45
**_Flucytosine 5-FC_** **Dosing Consideration**
100-150 mg/kg/day IV/PO in four divided doses **_RENAL DOSING ADJUSTMENT_** requires: **_TDM_** + not given as monotherapy
46
**Flucytosine 5-FC** **ADR / CI / MOnitoring**
ADR: **Rash / Diarrhea / LIVER toxicity _HEMATOLOGIC TOXICITY_** Monitor: **CBC / Creatine / urine LFT / Serum Levels**
47
**Which antifungal is** **CONTRAINDICATED with STATINS**?
**_ITRACONAZOLE_** CI w/ statins ***except PRAVAstatin*** Also avoid: **PPI + H2RA** **CYP3A4 Substrate + Inhibitor**
48
**Risk Factors for** **_Candidiasis_**
Use of: **_Broad Spectrum ABx_** **_Central Venous Catheters**_ + _**TPN_** **Dialysis / Neutropenia / _IMS_** Recent **_ItraAbdominal SURGERY_** **Prosthetic Devices** **Colonization @multiple sites (urine)**
49
**_Candidiasis_** **Empiric Treatment + Duration**
**_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
**Which Fungal Infection?** Commonly from: * *CATHETER** or **GI source** * remove central venous catheter if possible* **Fundoscopic Exam --\> EYE** **Mouth = Thursh** **Vulvovaginal** **Urine**
**_CANDIDIASIS_** Candida = **Budding ROUND Yeast** If in BLOOD = **CANDIDEMIA** treat ASAP \<12 hours = best mortality
51
**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)**
* *_ASPERGILLOSIS_** * *Acute Angle Septate BRANCHING** Common Species: **_A. FUMIGATUS_** \> **A. Flavus** \> **A. Niger**
52
**_Aspergillosis_** **DIAGNOSIS**
***_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
**_Aspergillosis_** **TREATMENT**
**_VORICONAZOLE_** 1st line **Isavuconazole = 2nd line** Other agents w/ Activity: **Amphotericin / Echinocandins**
54
**Which Fungal Infection?** Mainly affects: **Immunocompromised / AIDS patients** Presents as: **Meningitis / Pneumonia** Culture shows: **CAPSULE**
* *_CRYPTOCOCCAL DISEASE_** * *CAPSULE one** Diagnosed with: **_Cryptococcal Antigen Culture_**
55
**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
**_DIMORPHIC FUNGI_** **ENDEMIC DISEASE** **Specific Fungus depends on GEOGRAPHIC AREA**
56
**_CRYPTOCOCCAL DISEASE_** CAPSULE one ## Footnote **Treatment**
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
**_Dimorphic Fungi_** (**Endemics)** **INDUCTION TREATMENT** for **Severe Disease**
for **SEVERE disease:** **_AMPHOTERICIN B_** vvv May step down / consolidate therapy with **triazole**
58
**_Dimorphic Fungi_** (**Endemics)** **Non-Severe Treatment _Histoplasma Capsulatum_**
**_ITRACONAZOLE_**
59
**_Dimorphic Fungi_** (**Endemics)** **Non-Severe Treatment _Coccidioides Spp_**
**_ITRACONAZOLE_**
60
**_Dimorphic Fungi_** (**Endemics)** **Non-Severe Treatment _Blastomyces Dermatitidis_**
**_Fluconazole_** = **CNS** **_Voriconazole**_ or _**Itraconazole_**
61
**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*
* *_ZYGOMYCOSIS_** * *Mucor / Mucormycosis / Rhizopus** Found in: **Environment / DECAYING matter**
62
* *_ZYGOMYCOSIS_** * *Mucor / Mucormycosis / Rhizopus** ## Footnote **RISK FACTORS**
Found in: **Environment / DECAYING matter** **Long-Standing IMS state** or **Uncontrolled DIABETES** **TRAUMA / DEFEROXAMINE**
63
**_ZYGOMYCOSIS_** Mucor / Mucormycosis / Rhizopus ## Footnote **TREATMENT**
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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