Antifungals; L4 (12-07-15)

Question 1

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

Answer 1

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

Question 2

Systemic antifungal drugs for cutaneous fungal infections

1) *__
2) *__

Answer 2

Systemic antifungal drugs for cutaneous fungal infections

1) *Griseofulvin
2) *Terbinafine

Question 3

Topical antifungal drugs for cutaneous fungal infections

1) __: nystatin
2) __: miconazole, clotrimazole, terconazole
3) __ and __: terbinafine, naftifine, and butenafine

Answer 3

Topical antifungal drugs for cutaneous fungal infections

1) Polyene: nystatin
2) Azoles: miconazole, clotrimazole, terconazole
3) Allylamines and benzylamines: terbinafine, naftifine, and butenafine

Question 4

Amphotericin B Indications

1) __ spectrum
2) All ____ mycotic infections - Candida, Cryptococcus, Histoplasma, Blastomyces, Coccidioides, Aspergillus, Fusarium, Mucor
3) NOT __, NOT __
4) Treatment of choice: __

Answer 4

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

Question 5

Amphotericin B MOA

Binds to __ in fungal ____ and forms pores, causing increased membrane permeability and loss of cytoplasmic K+

Answer 5

Amphotericin B MOA

Binds to ergosterol in fungal plasma membrane and forms pores, causing increased membrane permeability and loss of cytoplasmic K+

Question 6

Amphotericin B Adverse Effects

1) __ related (Ampho-terrible): fever, chills, spasms, vomiting
2) __: nephrotoxicity/hepatoxicity/anemia

Answer 6

Amphotericin B Adverse Effects

1) Infusion related (Ampho-terrible): fever, chills, spasms, vomiting
2) Cumulative: nephrotoxicity/hepatoxicity/anemia

Question 7

Amphotericin B Misc

1) ONLY antifungal drug approved for use in __
2) Used for ____ therapy, followed by __ therapy with less toxic __

Answer 7

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

Question 8

Flucytosine Indications

1) __ spectrum: a) ____ - ESPECIALLY __ meningitis; b) __ sp
2) Agents of __

Answer 8

Flucytosine Indications

1) Narrow spectrum: a) Cryptococcus neoformans - ESPECIALLY cryptococcal meningitis; b) Candida sp
2) Agents of chromblastomycosis

Question 9

Flucytosine MOA

Taken up via __ __ and converted by fungal-specific cytosine deaminase to __ analogs that inhibit thymidylate synthase and __ __

Answer 9

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

Question 10

Flucytosine Adverse Effects

1) GI (__) - nausea/vomiting/diarrhea
2) __ toxicity - more common in those with __ disorders
3) __

Answer 10

Flucytosine Adverse Effects

1) GI (frequent) - nausea/vomiting/diarrhea
2) BM toxicity - more common in those with blood disorders
3) Tetratogenic

Question 11

Flucytosine Misc

1) __ CSF penetration
2) Used in combination with __
3) __ resistance
4) Dosage adjustment in __ failure
5) Not to be used in __

Answer 11

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

Question 12

Echinocandins Indications

1) __ including C. glabrata/C. kruseii
2) Tx of invasive __
3) Tx of invasive __
4) NO activity for __ or __ fungi

Answer 12

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

Question 13

Echinocandins MOA

1) Acts on fungal __ __
2) Inhibits B(1-3) D __ __ complex - impairs __ structure and increases __ instability

Answer 13

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

Question 14

Echinocandins Adverse Effects

1) __-tolerated
2) __-like effect with rapid infusion

Answer 14

Echinocandins (Caspofungin, Micafungin, Anidulafungin) Adverse Effects

1) Well-tolerated
2) Histamine-like effect with rapid infusion

Question 15

Echinocandins Misc

1) __ CSF penetration
2) Not to be used in __

Answer 15

Echinocandins (Caspofungin, Micafungin, Anidulafungin) Misc

1) Poor CSF penetration
2) Not to be used in pregnancy

Question 16

Griseofulvin Indications

Treatment of mycotic infections of skin, nail and hair due to __

Answer 16

Griseofulvin Indications

Treatment of mycotic infections of skin, nail and hair due to dermatophytes

Question 17

Griseofulvin MOA

1) Fungi__
2) Binds fungal __ and inhibits ____
3) Accumulates in newly differentiated __ producing cells, preventing fungal __

Answer 17

Griseofulvin MOA

1) Fungistatic
2) Binds fungal microtubules and inhibits mitotic spindle
3) Accumulates in newly differentiated keratin producing cells, preventing fungal growth

Question 18

Griseofulvin Adverse Effects

1) __ adverse effects
2) Headache, lethargy, __, blurred vision
3) Urticaria, __, rash
4) __toxicity
5) __penia, __penia, __cytosis
6) __ abnormalities

Answer 18

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

Question 19

Griseofulvin Misc

1) Very __
2) Strong CYP450 __ -> many drug interactions
3) Not to be used in __

Answer 19

Griseofulvin Misc

1) Very insoluble
2) Strong CYP450 inducer -> many drug interactions
3) Not to be used in pregnancy

Question 20

Terbinafine Indications

1) Treatment of __ and __ skin infections: a) __ __; b) __
2) Treatment of tinea __, tinea __, tinea __, and tinea __

Answer 20

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

Question 21

Terbinafine MOA

Inhibits fungal __ __, resulting in the formation of toxic products and inhibition of __ synthesis

Answer 21

Terbinafine MOA

Inhibits fungal squalene epoxidase, resulting in the formation of toxic products and inhibition of ergosterol synthesis

Question 22

Terbinafine Adverse Effects

1) __-tolerated
2) Adverse effects __ (__toxicity, __, Stevens Johnson)

Answer 22

Terbinafine Adverse Effects

1) Well-tolerated
2) Adverse effects rare (hepatotoxicity, neutropenia, Stevens Johnson)

Question 23

Terbinafine Misc

1) Long __
2) Not recommended in __/__ insufficiency

Answer 23

Terbinafine Misc

1) Long 1/2 life
2) Not recommended in hepatic/renal insufficiency

Question 24

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 __/__

Answer 24

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

Question 25

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*

Answer 25

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*

Question 26

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***

Answer 26

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**

Question 27

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 __ __

Answer 27

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

Question 28

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 __

Answer 28

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

Question 29

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: __

Answer 29

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: +

Question 30

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: __

Answer 30

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: -

Question 31

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: __

Answer 31

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: -

Question 32

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: __

Answer 32

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: -

Question 33

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: __

Answer 33

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: -

Question 34

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: __

Answer 34

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: +

Question 35

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: __

Answer 35

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: -

Question 36

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*

Answer 36

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*

Question 37

Tx of dermatophyte infections and onchomycosis Tinea pedis, corporis, cruris ("normal" patient): 1) __ antifungals, e.g., __ or __ 2) ***NOT __ (not active against dermatophytes)***

Answer 37

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)***

Question 38

Tx of dermatophyte infections and onchomycosis Tinea pedis, corporis, cruris (chronic/extensive disease; immunocompromised patient): 1) Oral __/__/__

Answer 38

Tx of dermatophyte infections and onchomycosis Tinea pedis, corporis, cruris (chronic/extensive disease; immunocompromised patient): 1) Oral terbinafine/itraconazole/fluconazole

Question 39

Tx of dermatophyte infections and onchomycosis Onchomycosis: 1) Oral __ or __ 2) 2nd line: oral __ or __ *Note: __ antifungals are INEFFECTIVE*

Answer 39

Tx of dermatophyte infections and onchomycosis Onchomycosis: 1) Oral terbinafine or itraconazole 2) 2nd line: oral fluconazole or griseofulvin *Note: topical antifungals are INEFFECTIVE*

Question 40

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**

Answer 40

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**

Question 41

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***

Answer 41

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***

Question 42

Fungal disease -> recommended tx Cryptococcosis: 1) Pulmonary/skin: __ OR __ 2) Meningitis: __ +/- __ (induction); __ (consolidation/maintenance)

Answer 42

Fungal disease -> recommended tx Cryptococcosis: 1) Pulmonary/skin: Fluconazole OR Amph B 2) Meningitis: Amph B +/- Flucytosine (induction); Fluconazole (consolidation/maintenance)

Question 43

Fungal disease -> recommended tx Aspergillosis: 1) Pulmonary/skin: __ 2) Invasive: a) __ OR __; b) __ (maintenance/alt. agent), __/__ (salvage)

Answer 43

Fungal disease -> recommended tx Aspergillosis: 1) Pulmonary/skin: itraconazole 2) Invasive: a) voriconazole OR amph B; b) itraconazole (maintenance/alt. agent), echinocandins/posaconazole (salvage)

Question 44

Fungal disease -> recommended tx Mucormycosis: -__ OR __ (salvage)

Answer 44

Fungal disease -> recommended tx Mucormycosis: -Amph B *or* Posaconazole (salvage)

Question 45

Fungal disease -> recommended tx Fusariosis: -__ OR __/__ (salvage)

Answer 45

Fungal disease -> recommended tx Fusariosis: -Amph B *or* Voriconazole/Posaconazole (salvage)

Question 46

**___** is the ONLY anti-fungal agent that is approved for use in the tx of **pregnant and/or breastfeeding women**.

Answer 46

**Amphotericin B** is the ONLY anti-fungal agent that is approved for use in the tx of **pregnant and/or breastfeeding women**.