Antifungals; L4 (12-07-15) Flashcards
Systemic antifungal drugs for systemic infections
1) __ antifungal agents: *amphotericin B
2) __ __: *5-flucytosine
3) __ antifungal agents: a) __ (ketoconazole); b) *__: *fluconazole, *itraconazole, *voriconazole, *posaconazole
4) __: *caspofungin, micafungin, anidulofungin
Systemic antifungal drugs for systemic infections
1) Polyene antifungal agents: *amphotericin B
2) Fluorinated pyrimidine: *5-flucytosine
3) Azole antifungal agents: a) imidazoles (ketoconazole); b) *triazoles: *fluconazole, *itraconazole, *voriconazole, *posaconazole
4) Echinocandins: *caspofungin, micafungin, anidulofungin
Systemic antifungal drugs for cutaneous fungal infections
1) *__
2) *__
Systemic antifungal drugs for cutaneous fungal infections
1) *Griseofulvin
2) *Terbinafine
Topical antifungal drugs for cutaneous fungal infections
1) __: nystatin
2) __: miconazole, clotrimazole, terconazole
3) __ and __: terbinafine, naftifine, and butenafine
Topical antifungal drugs for cutaneous fungal infections
1) Polyene: nystatin
2) Azoles: miconazole, clotrimazole, terconazole
3) Allylamines and benzylamines: terbinafine, naftifine, and butenafine
Amphotericin B Indications
1) __ spectrum
2) All ____ mycotic infections - Candida, Cryptococcus, Histoplasma, Blastomyces, Coccidioides, Aspergillus, Fusarium, Mucor
3) NOT __, NOT __
4) Treatment of choice: __
Amphotericin B Indications
1) Broad spectrum
2) All life-threatening mycotic infections - Candida, Cryptococcus, Histoplasma, Blastomyces, Coccidioides, Aspergillus, Fusarium, Mucor
3) NOT C. lusitaniae, NOT Pseudalerischeri boydii
4) Treatment of choice: mucormycosis
Amphotericin B MOA
Binds to __ in fungal ____ and forms pores, causing increased membrane permeability and loss of cytoplasmic K+
Amphotericin B MOA
Binds to ergosterol in fungal plasma membrane and forms pores, causing increased membrane permeability and loss of cytoplasmic K+
Amphotericin B Adverse Effects
1) __ related (Ampho-terrible): fever, chills, spasms, vomiting
2) __: nephrotoxicity/hepatoxicity/anemia
Amphotericin B Adverse Effects
1) Infusion related (Ampho-terrible): fever, chills, spasms, vomiting
2) Cumulative: nephrotoxicity/hepatoxicity/anemia
Amphotericin B Misc
1) ONLY antifungal drug approved for use in __
2) Used for ____ therapy, followed by __ therapy with less toxic __
Amphotericin B Misc
1) ONLY antifungal drug approved for use in pregnancy
2) Used for initial induction therapy, followed by consolidation therapy with less toxic azole
Flucytosine Indications
1) __ spectrum: a) ____ - ESPECIALLY __ meningitis; b) __ sp
2) Agents of __
Flucytosine Indications
1) Narrow spectrum: a) Cryptococcus neoformans - ESPECIALLY cryptococcal meningitis; b) Candida sp
2) Agents of chromblastomycosis
Flucytosine MOA
Taken up via __ __ and converted by fungal-specific cytosine deaminase to __ analogs that inhibit thymidylate synthase and __ __
Flucytosine MOA
Taken up via cytosine permease and converted by fungal-specific cytosine deaminase to 5-FU analogs that inhibit thymidylate synthase and RNA synthesis
Flucytosine Adverse Effects
1) GI (__) - nausea/vomiting/diarrhea
2) __ toxicity - more common in those with __ disorders
3) __
Flucytosine Adverse Effects
1) GI (frequent) - nausea/vomiting/diarrhea
2) BM toxicity - more common in those with blood disorders
3) Tetratogenic
Flucytosine Misc
1) __ CSF penetration
2) Used in combination with __
3) __ resistance
4) Dosage adjustment in __ failure
5) Not to be used in __
Flucytosine Misc
1) Good CSF penetration
2) Used in combination with Amph B
3) Frequent resistance
4) Dosage adjustment in renal failure
5) Not to be used in pregnancy
Echinocandins Indications
1) __ including C. glabrata/C. kruseii
2) Tx of invasive __
3) Tx of invasive __
4) NO activity for __ or __ fungi
Echinocandins (Caspofungin, Micafungin, Anidulafungin) Indications
1) Candida including C. glabrata/C. kruseii
2) Tx of invasive Candida
3) Tx of invasive Aspergillus
4) NO activity for Cryptococcus or dimorphic fungi
Echinocandins MOA
1) Acts on fungal __ __
2) Inhibits B(1-3) D __ __ complex - impairs __ structure and increases __ instability
Echinocandins (Caspofungin, Micafungin, Anidulafungin) MOA
1) Acts on fungal cell wall
2) Inhibits B(1-3) D glucan synthase complex - impairs membrane structure and increases osmotic instability
Echinocandins Adverse Effects
1) __-tolerated
2) __-like effect with rapid infusion
Echinocandins (Caspofungin, Micafungin, Anidulafungin) Adverse Effects
1) Well-tolerated
2) Histamine-like effect with rapid infusion
Echinocandins Misc
1) __ CSF penetration
2) Not to be used in __
Echinocandins (Caspofungin, Micafungin, Anidulafungin) Misc
1) Poor CSF penetration
2) Not to be used in pregnancy
Griseofulvin Indications
Treatment of mycotic infections of skin, nail and hair due to __
Griseofulvin Indications
Treatment of mycotic infections of skin, nail and hair due to dermatophytes
Griseofulvin MOA
1) Fungi__
2) Binds fungal __ and inhibits ____
3) Accumulates in newly differentiated __ producing cells, preventing fungal __
Griseofulvin MOA
1) Fungistatic
2) Binds fungal microtubules and inhibits mitotic spindle
3) Accumulates in newly differentiated keratin producing cells, preventing fungal growth
Griseofulvin Adverse Effects
1) __ adverse effects
2) Headache, lethargy, __, blurred vision
3) Urticaria, __, rash
4) __toxicity
5) __penia, __penia, __cytosis
6) __ abnormalities
Griseofulvin Adverse Effects
1) Many adverse effects
2) Headache, lethargy, vertigo, blurred vision
3) Urticaria, photosensitivity, rash
4) Hepatotoxicity
5) Leukopenia, neutropenia, monocytosis
6) Fetal abnormalities
Griseofulvin Misc
1) Very __
2) Strong CYP450 __ -> many drug interactions
3) Not to be used in __
Griseofulvin Misc
1) Very insoluble
2) Strong CYP450 inducer -> many drug interactions
3) Not to be used in pregnancy
Terbinafine Indications
1) Treatment of __ and __ skin infections: a) __ __; b) __
2) Treatment of tinea __, tinea __, tinea __, and tinea __
Terbinafine Indications
1) Treatment of onchomycosis and superficial skin infections: a) Candida Albicans; b) Dermatophytes
2) Treatment of tinea captis, tinea carpis, tinea cruris, and tinea pedis
Terbinafine MOA
Inhibits fungal __ __, resulting in the formation of toxic products and inhibition of __ synthesis
Terbinafine MOA
Inhibits fungal squalene epoxidase, resulting in the formation of toxic products and inhibition of ergosterol synthesis
Terbinafine Adverse Effects
1) __-tolerated
2) Adverse effects __ (__toxicity, __, Stevens Johnson)
Terbinafine Adverse Effects
1) Well-tolerated
2) Adverse effects rare (hepatotoxicity, neutropenia, Stevens Johnson)
Terbinafine Misc
1) Long __
2) Not recommended in __/__ insufficiency
Terbinafine Misc
1) Long 1/2 life
2) Not recommended in hepatic/renal insufficiency
Ketoconazole
MOA: Inhibition of __, which is involved in the synthesis of __, an essential component of fungal __
SOA: D__, C__ sp, C__, C__, H__, B__
CSF penetration: __
Renal dose adjustment: __
Drug interactions: __
Adverse effects: *__
Clinical uses: largely replaced by __; cheap 2nd-line agent for mucocutaneous __/__
Ketoconazole
MOA: Inhibition of 14-a-sterol demethylase, which is involved in the synthesis of ergosterol, an essential component of fungal membranes
SOA: Dermatophytes, Candida sp, Cryptococcus, Coccidioides, Histoplasma, Blastomyces
CSF penetration: No
Renal dose adjustment: No
Drug interactions: +++++
Adverse effects: *endocrine effects
Clinical uses: largely replaced by itraconazole; cheap 2nd-line agent for mucocutaneous Candidiasis/Dermatophytes
Fluconazole
MOA: Inhibition of __, which is involved in the synthesis of __, an essential component of fungal __
SOA: D__, C__ sp - C. G__ (+/-) C. k__ (-), C__, C__, H__ (+/-), B__ (+/-)
CSF penetration: __
Renal dose adjustment: __
Drug interactions: __
Adverse effects: __ adverse effects; __; nausea, skin rash, headache, GI symptoms
Clinical uses:
1) D__, O__
2) C__
3) Tx of choice: __ meningitis
4) __ meningitis
Fluconazole
MOA: Inhibition of 14-a-sterol demethylase, which is involved in the synthesis of ergosterol, an essential component of fungal membranes
SOA: Dermatophytes, Candida sp - C. Glabrata (+/-) C. krusei (-), Cryptococcus, Coccidioides, Histoplasma (+/-), Blastomyces (+/-)
CSF penetration: YES
Renal dose adjustment: YES
Drug interactions: ++
Adverse effects: Minor adverse effects; alopecia; nausea, skin rash, headache, GI symptoms
Clinical uses:
1) Dermatophytes, Onchomycosis
2) Candida
3) Tx of choice: cryptococcal meningitis
4) Coccidioidal meningitis
Itraconazole
MOA: Inhibition of __, which is involved in the synthesis of __, an essential component of fungal __
SOA: D__, C__ sp - C. G__ (+/-) C. k__ (+/-), C__, C__, H__, B__, P__ B__/S__ (+/-), A__ (+)
CSF penetration: \_\_ Renal dose adjustment: \_\_ Drug interactions: \_\_ Adverse effects: 1) ***\_\_/\_\_kalemia/peripheral \_\_*** 2) ***Contraindicated in \_\_/\_\_***
Clinical uses:
1) TOC: __
2) TOC: __
3) Non-meningeal __/__/__
4) NOT FOR __ meningitis
Itraconazole
MOA: Inhibition of 14-a-sterol demethylase, which is involved in the synthesis of ergosterol, an essential component of fungal membranes
SOA: Dermatophytes, Candida sp - C. Glabrata (+/-) C. krusei (+/-), Cryptococcus, Coccidioides, Histoplasma, Blastomyces, Pseudoallerischeri Boydii/Scedosporium (+/-), Aspergillus (+)
CSF penetration: No
Renal dose adjustment: No
Drug interactions: +++
Adverse effects:
1) HTN/hypokalemia/peripheral edema
2) Contraindicated in ventricular dysfunction/CHF
Clinical uses:
1) TOC: dermatophytes
2) TOC: onchomycosis
3) Non-meningeal blastomyces/histoplasma/coccidioides
4) NOT FOR cryptococcal meningitis
Voriconazole
MOA: Inhibition of __, which is involved in the synthesis of __, an essential component of fungal __
SOA: D__, C__ sp - incl C. G__ C. k__, C__, C__, H__, B__, P__ B__/S__, A__ (+++), F__
CSF penetration: \_\_ Renal dose adjustment: \_\_ Drug interactions: \_\_ Adverse effects: 1) **Photosensitivity, **rash, **periostitis, ***\_\_, ***\_\_, ***\_\_
Clinical uses:
1) TOC: Invasive __/__
2) Tx of __ __
Voriconazole
MOA: Inhibition of 14-a-sterol demethylase, which is involved in the synthesis of ergosterol, an essential component of fungal membranes
SOA: Dermatophytes, Candida sp - incl C. Glabrata C. krusei, Cryptococcus, Coccidioides, Histoplasma, Blastomyces, Pseudoallerischeri Boydii/Scedosporium, Aspergillus (+++), Fusarium
CSF penetration: YES Renal dose adjustment: No Drug interactions: +++ Adverse effects: 1) **Photosensitivity, **rash, **periostitis, ***visual changes, ***hallucination, ***seizures
Clinical uses:
1) TOC: Invasive Aspergillus/Fusarium
2) Tx of pseudoallerischeri boydii
Posaconazole
MOA: Inhibition of __, which is involved in the synthesis of __, an essential component of fungal __
SOA: D__, C__ sp - incl C. G__ C. k__, C__, C__, H__, B__, P__ B__/S__, A__ (+++), F__, M__
CSF penetration: __
Renal dose adjustment: __
Drug interactions: __
Adverse effects: __
Clinical uses:
1) Tx of invasive fungal infections - __/__
2) Antifungal prophylaxis in __
3) Salvage therapy for __
Posaconazole
MOA: Inhibition of 14-a-sterol demethylase, which is involved in the synthesis of ergosterol, an essential component of fungal membranes
SOA: Dermatophytes, Candida sp - incl C. Glabrata C. krusei, Cryptococcus, Coccidioides, Histoplasma, Blastomyces, Pseudoallerischeri Boydii/Scedosporium, Aspergillus (+++), Fusarium, Mucor
CSF penetration: No
Renal dose adjustment: No
Drug interactions: +++
Adverse effects: Well-tolerated
Clinical uses:
1) Tx of invasive fungal infections - Candida/Aspergillus
2) Antifungal prophylaxis in neutropenia
3) Salvage therapy for mucormycosis
Amphotericin B - SOA for systemic infections
Candida sp: __
C. glabrata: __
C. krusei: __
C. lusitaniae: __
Cryptococcus neoformans: __
Coccidioides sp: __
Blastomyces sp: __
Histoplasma sp: __
Aspergillus sp: __
Fusarium sp: __
Pseudallerischeri boydii/scedosporium apiospermum: __
Zygomyces/mucor: __
Amphotericin B - SOA for systemic infections
Candida sp: +
C. glabrata: +
C. krusei: +
C. lusitaniae: (-)
Cryptococcus neoformans: +
Coccidioides sp: +
Blastomyces sp: +
Histoplasma sp: +
Aspergillus sp: +
Fusarium sp: +
Pseudallerischeri boydii/scedosporium apiospermum: (-)
Zygomyces/mucor: +
Flucytosine - SOA for systemic infections
Candida sp: __
C. glabrata: __
C. krusei: __
C. lusitaniae: __
Cryptococcus neoformans: __
Coccidioides sp: __
Blastomyces sp: __
Histoplasma sp: __
Aspergillus sp: __
Fusarium sp: __
Pseudallerischeri boydii/scedosporium apiospermum: __
Zygomyces/mucor: __
Flucytosine - SOA for systemic infections
Candida sp: +
C. glabrata: +
C. krusei: +/-
C. lusitaniae: +
Cryptococcus neoformans: +
Coccidioides sp: -
Blastomyces sp: -
Histoplasma sp: -
Aspergillus sp: -
Fusarium sp: -
Pseudallerischeri boydii/scedosporium apiospermum: -
Zygomyces/mucor: -
Fluconazole - SOA for systemic infections
Candida sp: __
C. glabrata: __
C. krusei: __
C. lusitaniae: __
Cryptococcus neoformans: __
Coccidioides sp: __
Blastomyces sp: __
Histoplasma sp: __
Aspergillus sp: __
Fusarium sp: __
Pseudallerischeri boydii/scedosporium apiospermum: __
Zygomyces/mucor: __
Fluconazole - SOA for systemic infections
Candida sp: +
C. glabrata: +/-
C. krusei: -
C. lusitaniae: +
Cryptococcus neoformans: +
Coccidioides sp: +
Blastomyces sp: +/-
Histoplasma sp: +/-
Aspergillus sp: -
Fusarium sp: -
Pseudallerischeri boydii/scedosporium apiospermum: -
Zygomyces/mucor: -
Itraconazole - SOA for systemic infections
Candida sp: __
C. glabrata: __
C. krusei: __
C. lusitaniae: __
Cryptococcus neoformans: __
Coccidioides sp: __
Blastomyces sp: __
Histoplasma sp: __
Aspergillus sp: __
Fusarium sp: __
Pseudallerischeri boydii/scedosporium apiospermum: __
Zygomyces/mucor: __
Itraconazole - SOA for systemic infections
Candida sp: +
C. glabrata: +/-
C. krusei: +/-
C. lusitaniae: +
Cryptococcus neoformans: +
Coccidioides sp: +
Blastomyces sp: +
Histoplasma sp: +
Aspergillus sp: +
Fusarium sp: -
Pseudallerischeri boydii/scedosporium apiospermum: +/-
Zygomyces/mucor: -
Voriconazole - SOA for systemic infections
Candida sp: __
C. glabrata: __
C. krusei: __
C. lusitaniae: __
Cryptococcus neoformans: __
Coccidioides sp: __
Blastomyces sp: __
Histoplasma sp: __
Aspergillus sp: __
Fusarium sp: __
Pseudallerischeri boydii/scedosporium apiospermum: __
Zygomyces/mucor: __
Voriconazole - SOA for systemic infections
Candida sp: +
C. glabrata: +
C. krusei: +
C. lusitaniae: +
Cryptococcus neoformans: +
Coccidioides sp: +
Blastomyces sp: +
Histoplasma sp: +
Aspergillus sp: +
Fusarium sp: +
Pseudallerischeri boydii/scedosporium apiospermum: +
Zygomyces/mucor: -
Posaconazole - SOA for systemic infections
Candida sp: __
C. glabrata: __
C. krusei: __
C. lusitaniae: __
Cryptococcus neoformans: __
Coccidioides sp: __
Blastomyces sp: __
Histoplasma sp: __
Aspergillus sp: __
Fusarium sp: __
Pseudallerischeri boydii/scedosporium apiospermum: __
Zygomyces/mucor: __
Posaconazole - SOA for systemic infections
Candida sp: +
C. glabrata: +
C. krusei: +
C. lusitaniae: +
Cryptococcus neoformans: +
Coccidioides sp: +
Blastomyces sp: +
Histoplasma sp: +
Aspergillus sp: +
Fusarium sp: +
Pseudallerischeri boydii/scedosporium apiospermum: +
Zygomyces/mucor: +
Echocandins - SOA for systemic infections
Candida sp: __
C. glabrata: __
C. krusei: __
C. lusitaniae: __
Cryptococcus neoformans: __
Coccidioides sp: __
Blastomyces sp: __
Histoplasma sp: __
Aspergillus sp: __
Fusarium sp: __
Pseudallerischeri boydii/scedosporium apiospermum: __
Zygomyces/mucor: __
Echocandins - SOA for systemic infections
Candida sp: +
C. glabrata: +
C. krusei: +
C. lusitaniae: +
Cryptococcus neoformans: -
Coccidioides sp: -
Blastomyces sp: -
Histoplasma sp: -
Aspergillus sp: +
Fusarium sp: -
Pseudallerischeri boydii/scedosporium apiospermum: -
Zygomyces/mucor: -
Tx of dermatophyte infections and onchomycosis
Tinea captis (ringworm of the scalp):
1) Oral __ (long safety history)
2) Oral __
3) Oral __/__
Note: __ antifungals are INEFFECTIVE
Tx of dermatophyte infections and onchomycosis
Tinea captis (ringworm of the scalp):
1) Oral griseofulvin (long safety history)
2) Oral terbinafine
3) Oral fluconazole/itraconazole
Note: topical antifungals are INEFFECTIVE
Tx of dermatophyte infections and onchomycosis
Tinea pedis, corporis, cruris (“normal” patient):
1) __ antifungals, e.g., __ or __
2) NOT __ (not active against dermatophytes)
Tx of dermatophyte infections and onchomycosis
Tinea pedis, corporis, cruris (“normal” patient):
1) Topical antifungals, e.g., AZOLES or terbinafine
2) NOT nystatin (not active against dermatophytes)
Tx of dermatophyte infections and onchomycosis
Tinea pedis, corporis, cruris (chronic/extensive disease; immunocompromised patient):
1) Oral __/__/__
Tx of dermatophyte infections and onchomycosis
Tinea pedis, corporis, cruris (chronic/extensive disease; immunocompromised patient):
1) Oral terbinafine/itraconazole/fluconazole
Tx of dermatophyte infections and onchomycosis
Onchomycosis:
1) Oral __ or __
2) 2nd line: oral __ or __
Note: __ antifungals are INEFFECTIVE
Tx of dermatophyte infections and onchomycosis
Onchomycosis:
1) Oral terbinafine or itraconazole
2) 2nd line: oral fluconazole or griseofulvin
Note: topical antifungals are INEFFECTIVE
Fungal disease -> recommended tx
Endemic mycoses (Histoplasmosis/Blastomycosis/Coccidioidmycosis)
1) Mild/moderate: __ - e.g., __ (preferred)
2) Severely ill/disseminated: __ (induction) + __ (consolidation/maintenance)
Note: __ can be used to tx coccidioidmycosis and is DOC for disseminated disease/meningitis
Fungal disease -> recommended tx
Endemic mycoses (Histoplasmosis/Blastomycosis/Coccidioidmycosis):
1) Mild/moderate: an azole - e.g., itraconazole (preferred)
2) Severely ill/disseminated: amph B (induction) + an azole (consolidation/maintenance)
Note: fluconazole can be used to tx coccidioidmycosis and is DOC for disseminated disease/meningitis
Fungal disease -> recommended tx
Candidiasis:
1) Mucocutaneous (oral/vaginal/rash): initially a __ agent: __ or __, OR oral __ if __ tx is unsuccessful
2) Mild/moderate: __ OR another __
3) Severe disease: __ OR __ OR __
4) Meningitis: __ +/- __ (induction); __ (consolidation/maintenance); NOT __–poor CNS penetration
Fungal disease -> recommended tx
Candidiasis:
1) Mucocutaneous (oral/vaginal/rash): initially a topical agent: nystatin or an azole, OR oral fluconazole if topical tx is unsuccessful
2) Mild/moderate: fluconazole OR another azole
3) Severe disease: an azole OR amph B OR an echinocandin
4) Meningitis: Amph B +/- Flucytosine (induction); Fluconazole (consolidation/maintenance); NOT AN ECHINOCANDIN–poor CNS penetration
Fungal disease -> recommended tx
Cryptococcosis:
1) Pulmonary/skin: __ OR __
2) Meningitis: __ +/- __ (induction); __ (consolidation/maintenance)
Fungal disease -> recommended tx
Cryptococcosis:
1) Pulmonary/skin: Fluconazole OR Amph B
2) Meningitis: Amph B +/- Flucytosine (induction); Fluconazole (consolidation/maintenance)
Fungal disease -> recommended tx
Aspergillosis:
1) Pulmonary/skin: __
2) Invasive: a) __ OR __; b) __ (maintenance/alt. agent), __/__ (salvage)
Fungal disease -> recommended tx
Aspergillosis:
1) Pulmonary/skin: itraconazole
2) Invasive: a) voriconazole OR amph B; b) itraconazole (maintenance/alt. agent), echinocandins/posaconazole (salvage)
Fungal disease -> recommended tx
Mucormycosis:
-__ OR __ (salvage)
Fungal disease -> recommended tx
Mucormycosis:
-Amph B or Posaconazole (salvage)
Fungal disease -> recommended tx
Fusariosis:
-__ OR __/__ (salvage)
Fungal disease -> recommended tx
Fusariosis:
-Amph B or Voriconazole/Posaconazole (salvage)
___ is the ONLY anti-fungal agent that is approved for use in the tx of pregnant and/or breastfeeding women.
Amphotericin B is the ONLY anti-fungal agent that is approved for use in the tx of pregnant and/or breastfeeding women.
