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Pharmacology S1 Exam 5 > Antifungals; L4 (12-07-15) > Flashcards

Antifungals; L4 (12-07-15) Flashcards

1
Q

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

A

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

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2
Q

Systemic antifungal drugs for cutaneous fungal infections

1) *__
2) *__

A

Systemic antifungal drugs for cutaneous fungal infections

1) *Griseofulvin
2) *Terbinafine

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3
Q

Topical antifungal drugs for cutaneous fungal infections

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

A

Topical antifungal drugs for cutaneous fungal infections

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

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4
Q

Amphotericin B Indications

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

A

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

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5
Q

Amphotericin B MOA

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

A

Amphotericin B MOA

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

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6
Q

Amphotericin B Adverse Effects

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

A

Amphotericin B Adverse Effects

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

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7
Q

Amphotericin B Misc

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

A

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

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8
Q

Flucytosine Indications

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

A

Flucytosine Indications

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

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9
Q

Flucytosine MOA

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

A

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

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10
Q

Flucytosine Adverse Effects

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

A

Flucytosine Adverse Effects

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

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11
Q

Flucytosine Misc

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

A

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

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12
Q

Echinocandins Indications

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

A

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

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13
Q

Echinocandins MOA

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

A

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

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14
Q

Echinocandins Adverse Effects

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

A

Echinocandins (Caspofungin, Micafungin, Anidulafungin) Adverse Effects

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

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15
Q

Echinocandins Misc

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

A

Echinocandins (Caspofungin, Micafungin, Anidulafungin) Misc

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

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16
Q

Griseofulvin Indications

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

A

Griseofulvin Indications

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

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17
Q

Griseofulvin MOA

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

A

Griseofulvin MOA

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

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18
Q

Griseofulvin Adverse Effects

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

A

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

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19
Q

Griseofulvin Misc

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

A

Griseofulvin Misc

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

20
Q

Terbinafine Indications

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

A

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

21
Q

Terbinafine MOA

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

A

Terbinafine MOA

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

22
Q

Terbinafine Adverse Effects

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

A

Terbinafine Adverse Effects

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

23
Q

Terbinafine Misc

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

A

Terbinafine Misc

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

24
Q

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 __/__

A

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

25
Q

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

A

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

26
Q

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

A

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

27
Q

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 __ __

A

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

28
Q

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 __

A

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

29
Q

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: __

A

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: +

30
Q

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: __

A

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: -

31
Q

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: __

A

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: -

32
Q

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: __

A

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: -

33
Q

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: __

A

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: -

34
Q

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: __

A

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: +

35
Q

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: __

A

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: -

36
Q

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

A

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

37
Q

Tx of dermatophyte infections and onchomycosis

Tinea pedis, corporis, cruris (“normal” patient):

1) __ antifungals, e.g., __ or __
2) NOT __ (not active against dermatophytes)

A

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)

38
Q

Tx of dermatophyte infections and onchomycosis

Tinea pedis, corporis, cruris (chronic/extensive disease; immunocompromised patient):
1) Oral __/__/__

A

Tx of dermatophyte infections and onchomycosis

Tinea pedis, corporis, cruris (chronic/extensive disease; immunocompromised patient):
1) Oral terbinafine/itraconazole/fluconazole

39
Q

Tx of dermatophyte infections and onchomycosis

Onchomycosis:

1) Oral __ or __
2) 2nd line: oral __ or __

Note: __ antifungals are INEFFECTIVE

A

Tx of dermatophyte infections and onchomycosis

Onchomycosis:

1) Oral terbinafine or itraconazole
2) 2nd line: oral fluconazole or griseofulvin

Note: topical antifungals are INEFFECTIVE

40
Q

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

A

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

41
Q

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

A

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

42
Q

Fungal disease -> recommended tx

Cryptococcosis:

1) Pulmonary/skin: __ OR __
2) Meningitis: __ +/- __ (induction); __ (consolidation/maintenance)

A

Fungal disease -> recommended tx

Cryptococcosis:

1) Pulmonary/skin: Fluconazole OR Amph B
2) Meningitis: Amph B +/- Flucytosine (induction); Fluconazole (consolidation/maintenance)

43
Q

Fungal disease -> recommended tx

Aspergillosis:

1) Pulmonary/skin: __
2) Invasive: a) __ OR __; b) __ (maintenance/alt. agent), __/__ (salvage)

A

Fungal disease -> recommended tx

Aspergillosis:

1) Pulmonary/skin: itraconazole
2) Invasive: a) voriconazole OR amph B; b) itraconazole (maintenance/alt. agent), echinocandins/posaconazole (salvage)

44
Q

Fungal disease -> recommended tx

Mucormycosis:
-__ OR __ (salvage)

A

Fungal disease -> recommended tx

Mucormycosis:
-Amph B or Posaconazole (salvage)

45
Q

Fungal disease -> recommended tx

Fusariosis:
-__ OR __/__ (salvage)

A

Fungal disease -> recommended tx

Fusariosis:
-Amph B or Voriconazole/Posaconazole (salvage)

46
Q

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

A

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

Pharmacology S1 Exam 5 (5 decks)

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