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PHRM 865: Theraputics V > Lecture 24.1: Antifungal > Flashcards

Lecture 24.1: Antifungal Flashcards

1
Q

What are some of the common fungal pathogens?

A
  • Candida Sp.
  • Aspergillus Sp.
  • Cryptococcus Sp.
  • Zygomycetes Sp.
  • Endemic Fungi
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2
Q

What are the Candida fungi?

A
  • Ablicans
  • Glabrata
  • Parapsilosis
  • Tropicalis
  • Krusei [resists fluconizole]
  • Guilliermondii
  • Lusitaniae
  • Auris [Multidrug resistant]
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3
Q

What is important to know about Aspergillus Fungi?

A
  • MOLD
  • Causes disease in immunocompromised hosts
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4
Q

What is important to know about Cryptococcus fungi?

A
  • Yeast infections that can cause CNS & respiratory tract infections
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5
Q

What are the Zygomycetes and what is important to know about them?

-

A
  • Rhizopus, Abisdia, Mucor, Rhizomucor
  • Manily cause by like injuries from natural disasters
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6
Q

What are some fo the Endemic [pathogenic] fungi?

A
  • Histoplasma Capsulatum [Midwestern]
  • Blastomuces Sp. [Southeastern and Midwestern]
  • Coccidioides Immities [Southwestern]

Different geo locations for each fungi

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7
Q

What is the mechanism of aciton for Amphotericin B?

A
  • Binds to ergoterola and inserts into the fungal membrane –> increased leakage –> Cell Death
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8
Q

What is the spectrum of activity for Amphotericin B?

A
  • Candida Sp. [not Lusitaniae]
  • Cryptococcus Neoformans
  • Blastomyces Demartitidis
  • Histoplasma Capsulatum
  • Coocidioides Immitis
  • Aspergillus Sp. [less to Terreus]
  • Mucor Sp.
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9
Q

What are some of the pharmacokinetic for Amphotericin B?

A
  • Poor orally = NEED IV
  • Widely distributed [liver, spleen, bone marrow…] but POOR INTO CSF
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10
Q

What are some of the clinical uses for Amphotericin B?

A
  • Candida Sp. [not Lusitaniae]
  • Cryptococcus Neoformans
  • Blastomyces Demartitidis
  • Histoplasma Capsulatum
  • Coocidioides Immitis
  • Aspergillus Sp. [less to Terreus]
  • Mucor Sp.

Same as the spectrum

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11
Q

What is important to do for dosing and administration for Amphotericin B?

-

A
  • Give a test dose [NO pretreat]
  • PRETREAT BEFORE actual dose
  • Dose Based on ideal body weight
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12
Q

What are some of the adverse effects of Amphotericin B?

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A
  • Infusion related [headache, fever chills, nausea ,vomiting, hypotension] =why we pretreat
  • Thrombophlebitis
  • Nephrotoxicity
  • Hypokalemia
  • Hypomagnesemia
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13
Q

What is the mechanism of aciton for Flucytosine?

A
  • Flucytosine enters cell –> becomes 5-FU –> affects protein synthesis
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14
Q

What is spectrum of activity of Flucytosine?

A
  • Cryptococcus Neoformans
  • Candida Sp.
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15
Q

What is the pharmcokinetics fro Flucytosine?

A
  • Well absorbed orally
  • Penetrates into CSF
  • Excerted unchanged in the urine
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16
Q

What is the clinical use for Flucytosine?

A
  • Primarily in combo with Amp B [but mainly for Crytococcus Neoformins?]
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17
Q

What are the adverse effects for Flucytosine?

A
  • GI [nausea, vomiting, diarrhea, AB Pain…]
  • Hematologic [bone marrow suppression]
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18
Q

What is important to know the dosing and monitioring for Flucytosine?

A
  • Normal: 100-150mg mg/kg/day PO in QID
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19
Q

What is the mechanism of action for Ketoconazole?

A
  • Inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth
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20
Q

What is the spectrum of activity for Ketoconazole?

A
  • Candida Albicans
  • Cryptococcus Neoformans
  • Histoplasma Capsulatum
  • Dermatophytes
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21
Q

What is the Pharmacokinetics for Ketoconazole?

A
  • Well absorbed; invresely related to gastric pH
  • Widely in the body; NO CSF
  • Metabolized in Liver
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22
Q

What are the clinical uses for ketoconazole?

A
  • NEVER 1st line for fungal
  • Candidiasis
  • Histoplasma
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23
Q

What are some of the adverse effects for Ketoconazole?

A
  • GI [N/V/D]
  • Hepatotoxicity
  • Endocrine

Very potent 3A4 inhibitor

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24
Q

What is the mechanism of action for Itraconzole?

A
  • Inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth
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24
Q
A
25
Q

What is the specturm of activity for Itraconazole?

A
  • Aspergillus Sp. [not really used for this]
  • Histoplasma Capsulatum [Drug of Choice]
  • Blastomyces Dermtitidis
  • Candida Sp.
  • Coccidioides Immitis
  • Cryptococcis Neoformans
  • Sporothrix Sxhenckii [Roses thorns]
26
Q

What is the pharmacokinetics for Itraconazole?

A
  • Good orally -Dependent on Gastric Acid
  • Soultion NOT affected by Gastric Acid
  • Suba-itraconazole NOT affected by gastric acif
  • Widely Disturbed
  • Metabolized by 3A4

ACTIVE METABOLITE = hydroxitraconazole

27
Q

Whar are the Clinical uses for Itraconazole?

A
  • Histoplasmaosis [1st line]
  • Aspergillosis [not 1st line]
  • Bastomycosis
  • Life threatening ifections
  • Toenail and Fingernail fungus
28
Q

What are some of the important Therapeutic drug monitoring for Itraconazole?

A
  • Serum Trough conc. > 0.5-1 associated with efficacy
29
Q

What are the adverse effects for Itaconazole?

A
  • Hepatotoxicity
  • CHF [boxed warning]
  • QTc Prolongation
  • Nausea
  • Rash
30
Q

What are some of the drug interactions for Itraconazole?

A
  • H2RAs & PPIs = decease absorption of CAPSULES
  • POTENT INHIBITOR of 3A4
31
Q

What is the mechanism of action for Fluconazole?

A
  • Inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth
32
Q

What is the spectrum of activity for Fluconazole?

A
  • Candida Sp. [less to Glabrata; NOT to Krusei]
  • Cryptococcus Neofromans
  • Histoplasma Capsulatum
  • Blastomyces Dermatitidis
  • Coccidoides Immitis
33
Q

What is the Pharmacokinetics for Fluconazole?

A
  • Well absorbed orally [Independent of gastric acid]
  • Does get into CSF
  • Excreted unchaged in the urine
  • Dosage reduction for renal issues
33
Q

What are some of the clinical uses and dosing for Fluconazole?

A
  • Candidiasis [nonivasive and invasive]
  • Cryptococcal Meningitis [For Induction; Consolidation (800mg for 10-12w); Maintenance (400mg for 1y)

DOSE TOTAL BODY WEIGHT

34
Q

What are some of the adverse effects for Fluconazole?

A
  • Headache, Nausea, Anorexia
  • QTc Prolongation
35
Q

What is the mechansim of action for Voriconazole?

A
    • Inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth
36
Q

What is the spectrum of activity for Voriconazole?

A
  • Aspergillus Sp.
  • Scedosporium Apospermum
  • Candida Sp.
  • Histoplasma Capsulatum
  • Blastomyces Dermatitidis
  • Crpytociccus Neoformans
  • Fusaeium Sp.
37
Q

What is the pharmacokinetics for Voriconazole?

A
  • Good Orally [not affected by H2RAs or PPIs]
  • Metabolized by 2C19, 2C9, 3A4
  • Non-linear
  • AVOID IV IF CrCl < 50ml/min
38
Q

What are some of the adverse effects for Voriconazole?

A
  • Visusal Disturbances
  • Elevated liver tests
  • QTc Prolongation
  • Skin reactions
  • Periostitis
39
Q

What are some of the drug interaction for Voriconazole?

A
  • 3A4, 2C9, 2C19
40
Q

What is the mechanism of action for Posaconaole?

A
    • Inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth
41
Q

What is the spectrum of activity for Posaconazole?

A
  • Candida Sp.
  • Aspergillus Sp.
  • Cryptococcus Neoformans
  • Histoplasma Capsulatum
  • Mucor Sp.
  • Coccidioides Sp.
42
Q

What is the pharmacokinetics for Posaconazole?

A
  • Delayed Release = Preferred Oral Form
  • AVOD if CrCl < 50
43
Q

What are some of the drug interactions for Posaconazole?

A
  • STRONG 3A4 Inhibitor
44
Q

What are some of the adverse effects for Posaconazole?

A
  • Nausea, Vomiting, Ab pain, Diarrhea
  • QTc Prolongation
  • Rash
45
Q

What is the mechanism of actino for Isavuconazole?

A
  • PRODRUG that inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth

Prodrug = Isavuconazonium Sulfate

46
Q

What is the Spectrum of activity for isavuconazole?

A
  • Aspergillus Sp.
  • Mucor
  • Rhizopus
47
Q

What is the pharmacokineitcs for Isavuconaole?

A
  • Linear
  • Well Absorbed orally; IV and PO eqaul
  • NO dosage adjustment for renal issues
  • IV DOES NOT have cyclodextrin
48
Q

What are some of the adverse effects for Isavuconazle?

A
  • Nausea, Vomiting, Diasrrheam Headache
  • DOES NOT cause QTc Prolongation
49
Q

What are some of the contraindicataions for Isavuconazole?

A
  • 3A4 inhibitors = increased conc.
  • 3A4 inducers = decreased conc.
  • Shortens QT interval
50
Q

What are the Echinocandin Antifungal Agents that are used?

A
  • Capsofungin
  • Maicafungin
  • Anidulafungin
51
Q

What is the mechanism of action for the Enhinocandin Antifungal Agents?

A
  • Glucan synthesis inhibitor –> noncompetitive inhibition of 1,3-b-D-glucan [part of fungal cell wall = Fungicidal
52
Q

What is the spectrum of activity for the Enhinocandin Antifungal Agents?

A
  • Aspergillus Sp.
  • Candida Sp. [even azole resistant]
  • Limited activity to Histoplasma Capsulatum, Cryptococcus Neoformans, Fusarium, Mucor
53
Q

What is the pharmacokinetics for Caspofungin?

A
  • Poor Orally = NEEDS IV
  • NO dosage adjustment
  • NOT removed during hemo
54
Q

What are the clinical indications for Caspofungin?

A
  • Candidemia
  • Empiric Therapy for fungal febrile neutropenia
  • Invasve Aspergillosis
55
Q

What are some of the drug interactions for Caspofungin?

A
  • DONT induce or inhibit P450
  • Tacrolimus = decreased
  • Cyclosporine = Increased Caspo AUC
56
Q

What are some of the adverse effects for Caspofungin?

A
  • Rash, Facial Swelling, Pruritus Flushing
  • Fever
  • Phlebitis
  • Nausea, Vomiting, Headache
57
Q

What is the pharmacokinetics for Micafungin?

A
  • NOT good orally = NEED IV
  • Half life 14-17h
  • Metabloized in Liver
  • <15% excreated renal
58
Q

What are the adverse effects for Micafungin?

A
  • Hyperbilirubnemia
  • Nausea
  • Diarrhea
  • Eosinophila
  • Rash
59
Q

What are the pharmacokinetics for Anidulafungin?

A
  • NOT good orally = NEED IV
  • Half life 26.5h
  • NOT Metabloized or Eliminated Renally

PHRM 865: Theraputics V (42 decks)

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