Lecture 24.1: Antifungal Flashcards
What are some of the common fungal pathogens?
- Candida Sp.
- Aspergillus Sp.
- Cryptococcus Sp.
- Zygomycetes Sp.
- Endemic Fungi
What are the Candida fungi?
- Ablicans
- Glabrata
- Parapsilosis
- Tropicalis
- Krusei [resists fluconizole]
- Guilliermondii
- Lusitaniae
- Auris [Multidrug resistant]
What is important to know about Aspergillus Fungi?
- MOLD
- Causes disease in immunocompromised hosts
What is important to know about Cryptococcus fungi?
- Yeast infections that can cause CNS & respiratory tract infections
What are the Zygomycetes and what is important to know about them?
-
- Rhizopus, Abisdia, Mucor, Rhizomucor
- Manily cause by like injuries from natural disasters
What are some fo the Endemic [pathogenic] fungi?
- Histoplasma Capsulatum [Midwestern]
- Blastomuces Sp. [Southeastern and Midwestern]
- Coccidioides Immities [Southwestern]
Different geo locations for each fungi
What is the mechanism of aciton for Amphotericin B?
- Binds to ergoterola and inserts into the fungal membrane –> increased leakage –> Cell Death
What is the spectrum of activity for Amphotericin B?
- Candida Sp. [not Lusitaniae]
- Cryptococcus Neoformans
- Blastomyces Demartitidis
- Histoplasma Capsulatum
- Coocidioides Immitis
- Aspergillus Sp. [less to Terreus]
- Mucor Sp.
What are some of the pharmacokinetic for Amphotericin B?
- Poor orally = NEED IV
- Widely distributed [liver, spleen, bone marrow…] but POOR INTO CSF
What are some of the clinical uses for Amphotericin B?
- Candida Sp. [not Lusitaniae]
- Cryptococcus Neoformans
- Blastomyces Demartitidis
- Histoplasma Capsulatum
- Coocidioides Immitis
- Aspergillus Sp. [less to Terreus]
- Mucor Sp.
Same as the spectrum
What is important to do for dosing and administration for Amphotericin B?
-
- Give a test dose [NO pretreat]
- PRETREAT BEFORE actual dose
- Dose Based on ideal body weight
What are some of the adverse effects of Amphotericin B?
-
- Infusion related [headache, fever chills, nausea ,vomiting, hypotension] =why we pretreat
- Thrombophlebitis
- Nephrotoxicity
- Hypokalemia
- Hypomagnesemia
What is the mechanism of aciton for Flucytosine?
- Flucytosine enters cell –> becomes 5-FU –> affects protein synthesis
What is spectrum of activity of Flucytosine?
- Cryptococcus Neoformans
- Candida Sp.
What is the pharmcokinetics fro Flucytosine?
- Well absorbed orally
- Penetrates into CSF
- Excerted unchanged in the urine
What is the clinical use for Flucytosine?
- Primarily in combo with Amp B [but mainly for Crytococcus Neoformins?]
What are the adverse effects for Flucytosine?
- GI [nausea, vomiting, diarrhea, AB Pain…]
- Hematologic [bone marrow suppression]
What is important to know the dosing and monitioring for Flucytosine?
- Normal: 100-150mg mg/kg/day PO in QID
What is the mechanism of action for Ketoconazole?
- Inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth
What is the spectrum of activity for Ketoconazole?
- Candida Albicans
- Cryptococcus Neoformans
- Histoplasma Capsulatum
- Dermatophytes
What is the Pharmacokinetics for Ketoconazole?
- Well absorbed; invresely related to gastric pH
- Widely in the body; NO CSF
- Metabolized in Liver
What are the clinical uses for ketoconazole?
- NEVER 1st line for fungal
- Candidiasis
- Histoplasma
What are some of the adverse effects for Ketoconazole?
- GI [N/V/D]
- Hepatotoxicity
- Endocrine
Very potent 3A4 inhibitor
What is the mechanism of action for Itraconzole?
- Inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth
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]
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
ACTIVE METABOLITE = hydroxitraconazole
Whar are the Clinical uses for Itraconazole?
- Histoplasmaosis [1st line]
- Aspergillosis [not 1st line]
- Bastomycosis
- Life threatening ifections
- Toenail and Fingernail fungus
What are some of the important Therapeutic drug monitoring for Itraconazole?
- Serum Trough conc. > 0.5-1 associated with efficacy
What are the adverse effects for Itaconazole?
- Hepatotoxicity
- CHF [boxed warning]
- QTc Prolongation
- Nausea
- Rash
What are some of the drug interactions for Itraconazole?
- H2RAs & PPIs = decease absorption of CAPSULES
- POTENT INHIBITOR of 3A4
What is the mechanism of action for Fluconazole?
- Inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth
What is the spectrum of activity for Fluconazole?
- Candida Sp. [less to Glabrata; NOT to Krusei]
- Cryptococcus Neofromans
- Histoplasma Capsulatum
- Blastomyces Dermatitidis
- Coccidoides Immitis
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
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)
DOSE TOTAL BODY WEIGHT
What are some of the adverse effects for Fluconazole?
- Headache, Nausea, Anorexia
- QTc Prolongation
What is the mechansim of action for Voriconazole?
- Inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth
What is the spectrum of activity for Voriconazole?
- Aspergillus Sp.
- Scedosporium Apospermum
- Candida Sp.
- Histoplasma Capsulatum
- Blastomyces Dermatitidis
- Crpytociccus Neoformans
- Fusaeium Sp.
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
What are some of the adverse effects for Voriconazole?
- Visusal Disturbances
- Elevated liver tests
- QTc Prolongation
- Skin reactions
- Periostitis
What are some of the drug interaction for Voriconazole?
- 3A4, 2C9, 2C19
What is the mechanism of action for Posaconaole?
- Inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth
What is the spectrum of activity for Posaconazole?
- Candida Sp.
- Aspergillus Sp.
- Cryptococcus Neoformans
- Histoplasma Capsulatum
- Mucor Sp.
- Coccidioides Sp.
What is the pharmacokinetics for Posaconazole?
- Delayed Release = Preferred Oral Form
- AVOD if CrCl < 50
What are some of the drug interactions for Posaconazole?
- STRONG 3A4 Inhibitor
What are some of the adverse effects for Posaconazole?
- Nausea, Vomiting, Ab pain, Diarrhea
- QTc Prolongation
- Rash
What is the mechanism of actino for Isavuconazole?
- PRODRUG that inhibits the synthesis of ergosterol –> leakage of cytoplasm –> Inhibition of growth
Prodrug = Isavuconazonium Sulfate
What is the Spectrum of activity for isavuconazole?
- Aspergillus Sp.
- Mucor
- Rhizopus
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
What are some of the adverse effects for Isavuconazle?
- Nausea, Vomiting, Diasrrheam Headache
- DOES NOT cause QTc Prolongation
What are some of the contraindicataions for Isavuconazole?
- 3A4 inhibitors = increased conc.
- 3A4 inducers = decreased conc.
- Shortens QT interval
What are the Echinocandin Antifungal Agents that are used?
- Capsofungin
- Maicafungin
- Anidulafungin
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
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
What is the pharmacokinetics for Caspofungin?
- Poor Orally = NEEDS IV
- NO dosage adjustment
- NOT removed during hemo
What are the clinical indications for Caspofungin?
- Candidemia
- Empiric Therapy for fungal febrile neutropenia
- Invasve Aspergillosis
What are some of the drug interactions for Caspofungin?
- DONT induce or inhibit P450
- Tacrolimus = decreased
- Cyclosporine = Increased Caspo AUC
What are some of the adverse effects for Caspofungin?
- Rash, Facial Swelling, Pruritus Flushing
- Fever
- Phlebitis
- Nausea, Vomiting, Headache
What is the pharmacokinetics for Micafungin?
- NOT good orally = NEED IV
- Half life 14-17h
- Metabloized in Liver
- <15% excreated renal
What are the adverse effects for Micafungin?
- Hyperbilirubnemia
- Nausea
- Diarrhea
- Eosinophila
- Rash
What are the pharmacokinetics for Anidulafungin?
- NOT good orally = NEED IV
- Half life 26.5h
- NOT Metabloized or Eliminated Renally
