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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?

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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
25
What is the specturm of activity for Itraconazole?
- 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
What is the pharmacokinetics for Itraconazole?
- Good orally -**Dependent on Gastric Acid** - Soultion NOT affected by Gastric Acid - Suba-itraconazole NOT affected by gastric acif - Widely Disturbed - Metabolized by 3A4 ## Footnote **ACTIVE METABOLITE = hydroxitraconazole**
27
Whar are the Clinical uses for Itraconazole?
- **Histoplasmaosis [1st line]** - Aspergillosis [not 1st line] - Bastomycosis - Life threatening ifections - **Toenail and Fingernail** fungus
28
What are some of the important Therapeutic drug monitoring for Itraconazole?
- **Serum Trough conc. > 0.5-1 associated with efficacy**
29
What are the adverse effects for Itaconazole?
- **Hepatotoxicity** - **CHF** [boxed warning] - **QTc Prolongation** - Nausea - Rash
30
What are some of the drug interactions for Itraconazole?
- H2RAs & PPIs = decease absorption of **CAPSULES** - **POTENT INHIBITOR of 3A4**
31
What is the mechanism of action for Fluconazole?
- Inhibits the synthesis of ergosterol --> leakage of cytoplasm --> Inhibition of growth
32
What is the spectrum of activity for Fluconazole?
- **Candida Sp**. [less to Glabrata; NOT to Krusei] - **Cryptococcus Neofromans** - Histoplasma Capsulatum - Blastomyces Dermatitidis - **Coccidoides Immitis**
33
What is the Pharmacokinetics for Fluconazole?
- Well absorbed orally [**Independent of gastric acid**] - Does get into CSF - Excreted unchaged in the urine - **Dosage reduction for renal issues**
33
What are some of the clinical uses and dosing for Fluconazole?
- Candidiasis [nonivasive and invasive] - **Cryptococcal Meningitis** [For Induction; Consolidation (800mg for 10-12w); Maintenance (400mg for 1y) ## Footnote **DOSE TOTAL BODY WEIGHT**
34
What are some of the adverse effects for Fluconazole?
- Headache, Nausea, Anorexia - **QTc Prolongation**
35
What is the mechansim of action for Voriconazole?
- - Inhibits the synthesis of ergosterol --> leakage of cytoplasm --> Inhibition of growth
36
What is the spectrum of activity for Voriconazole?
- **Aspergillus Sp.** - Scedosporium Apospermum - Candida Sp. - Histoplasma Capsulatum - Blastomyces Dermatitidis - Crpytociccus Neoformans - **Fusaeium Sp.**
37
What is the pharmacokinetics for Voriconazole?
- Good Orally [**not affected by H2RAs or PPIs**] - Metabolized by **2C19, 2C9, 3A4** - **Non-linear** - **AVOID IV IF CrCl < 50ml/min**
38
What are some of the adverse effects for Voriconazole?
- Visusal Disturbances - Elevated liver tests - QTc Prolongation - Skin reactions - Periostitis
39
What are some of the drug interaction for Voriconazole?
- **3A4, 2C9, 2C19**
40
What is the mechanism of action for Posaconaole?
- - Inhibits the synthesis of ergosterol --> leakage of cytoplasm --> Inhibition of growth
41
What is the spectrum of activity for Posaconazole?
- Candida Sp. - **Aspergillus Sp.** - Cryptococcus Neoformans - Histoplasma Capsulatum - **Mucor Sp.** - Coccidioides Sp.
42
What is the pharmacokinetics for Posaconazole?
- Delayed Release = **Preferred Oral Form** - **AVOD if CrCl < 50**
43
What are some of the drug interactions for Posaconazole?
- STRONG 3A4 Inhibitor
44
What are some of the adverse effects for Posaconazole?
- Nausea, Vomiting, Ab pain, Diarrhea - **QTc Prolongation** - Rash
45
What is the mechanism of actino for Isavuconazole?
- **PRODRUG** that inhibits the synthesis of ergosterol --> leakage of cytoplasm --> Inhibition of growth ## Footnote Prodrug = Isavuconazonium Sulfate
46
What is the Spectrum of activity for isavuconazole?
- Aspergillus Sp. - Mucor - Rhizopus
47
What is the pharmacokineitcs for Isavuconaole?
- **Linear** - Well Absorbed orally; **IV and PO eqaul** - **NO** dosage adjustment for renal issues - IV **DOES NOT** have cyclodextrin
48
What are some of the adverse effects for Isavuconazle?
- Nausea, Vomiting, Diasrrheam Headache - **DOES NOT** cause QTc Prolongation
49
What are some of the contraindicataions for Isavuconazole?
- 3A4 inhibitors = increased conc. - 3A4 inducers = decreased conc. - **Shortens QT interval**
50
What are the Echinocandin Antifungal Agents that are used?
- Capsofungin - Maicafungin - Anidulafungin
51
What is the mechanism of action for the Enhinocandin Antifungal Agents?
- Glucan synthesis inhibitor --> noncompetitive inhibition of 1,3-b-D-glucan [part of fungal **cell wall** = Fungicidal
52
What is the spectrum of activity for the Enhinocandin Antifungal Agents?
- **Aspergillus Sp.** - Candida Sp. [even azole resistant] - **Limited activity to Histoplasma Capsulatum, Cryptococcus Neoformans, Fusarium, Mucor**
53
What is the pharmacokinetics for Caspofungin?
- Poor Orally = NEEDS IV - NO dosage adjustment - NOT removed during hemo
54
What are the clinical indications for Caspofungin?
- Candidemia - Empiric Therapy for fungal febrile neutropenia - Invasve Aspergillosis
55
What are some of the drug interactions for Caspofungin?
- DONT induce or inhibit P450 - Tacrolimus = decreased - Cyclosporine = Increased Caspo AUC
56
What are some of the adverse effects for Caspofungin?
- Rash, Facial Swelling, Pruritus Flushing - Fever - Phlebitis - Nausea, Vomiting, Headache
57
What is the pharmacokinetics for Micafungin?
- NOT good orally = NEED IV - Half life 14-17h - Metabloized in Liver - <15% excreated renal
58
What are the adverse effects for Micafungin?
- Hyperbilirubnemia - Nausea - Diarrhea - Eosinophila - Rash
59
What are the pharmacokinetics for Anidulafungin?
- NOT good orally = NEED IV - Half life 26.5h - NOT Metabloized or Eliminated Renally

PHRM 865: Theraputics V (42 decks)

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