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Anti-Fungal / Anti-Protozoal Flashcards

1
Q

Unlike bacteria, fungi are _____, with rigid cell walls composed largely of ____

A

eukaryotic , chitin

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2
Q

What does fungal cell membranes contain?

A

ergosterol

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3
Q

Name the 4 drug classes for subcutaneous and systemic mycotic infections

A

Amphotericin B
Antimetabolite antifungals (Flucytosine)
Echinocandins (Caspofungin)
Azole Antifungals (Triazoles)

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4
Q

Name the 3 drug classes for cutaneous mycotic infections

A

Nystatin
Squalene epoxidase inhibitors (Terbinafine)
Azole antifungals (Imidazoles)

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5
Q

Amphotericin B is a naturally occurring ______ anti fungal produced by Stroptomyces nodosus

A

polyene

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6
Q

Amphotericin B MOA

A

binds to ergosterol in plasma membranes of sensitive fungal cells to forms pores –> disrupt membrane function, allowing electrolytes and small molecules to leak from the cell, resulting in cell death

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7
Q

Amphotericin B is fungicidal or fungistatic?

A

fungicidal: high conc
fungistatic: low conc

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8
Q

Amphotericin B is active against

A

Candida albicans (Candidiasis)
Histoplasmosis
cryptococcus neoformans
aspergillus (Aspergilloses)

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9
Q

Common indiction for Amphotericin B

A

oral candidiasis alongside nystatin

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10
Q

Amphotericin B administration

A

Topical or slow IV infusion as GI absorption is negligible for all formulations

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11
Q

Amphotericin B is ____ in water

A

insoluble

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12
Q

Amphotericin B excretion

A

Urine and some via bile

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13
Q

Amphotericin B dose adjustment for renal dysfunction

A

TDD 50%

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14
Q

Amphotericin B ADR (Name 4)

A 
Fever and chills
nephrotoxicity 
hypotension 
thrombophlebitis 
ototoxicity
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15
Q

Amphotericin B Preggo?

A

Cat B

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16
Q

Name an antimetabolite Antifungals

A

5-Flucytosine

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17
Q

5-Flucytosine is _____-soluble

A

water

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18
Q

5-Flucytosine MOA

A

enters fungal cells through cytosine specific permeases –> converted by cytosine deaminase to 5-fluorouracil –> incorporated into fungal RNA –> 5-fluorodeoxyuridine monophosphate (a potent inhibitor of thymidylate synthase)

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19
Q

5-FC is fungi_____

A

static

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20
Q

5-Flucytosine is effective in combination with ___ for treating __________ and _________

A

amphotericin B, Candidiasis, cryptococcosis

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21
Q

5-Flucytosine absorption

A

oral

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22
Q

5-Flucytosine CSF?

A

yes

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23
Q

mechanism of resistance for 5-Flucytosine

A

Decreased levels of any of the enzymes in conversion to 5-FC

Used in combination with amphotericin B

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24
Q

5-Flucytosine ADR

A

GI
bone marrow suppression (monitor leukocytes and platelets weekly
hepatotoxicity

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25
5-Flucytosine preggo
Cat C
26
Name 3 echinocandins
caspofungin micafungin anidulafungin
27
MOA of Echinocandins
inhibit the activity of the gluten synthase complex, resulting in the loss of the structural integrity of the cell wall
28
Echinocandins oral bioavailability
poor
29
Echinocandins CSF?
yes
30
Echinocandins broad or narrow activity?
broad spectrum
31
Echinocandins have potent activity against which species
aspergillus and most candidia species including those species resistant to azaleas
32
Echinocandins preggo
cat C
33
Caspofungin administration
IV
34
Caspofungin use
first line option for patients with invasive candidiasis including candidemia second line option for invasive aspergillosis in patients who have failed or cannot tolerate amphotericin B or an azalea
35
Caspofungin elimination
urine and faeces
36
Caspofungin metabolised by CYP450?
no
37
Caspofungin metabolised by.....
hydrolysis and N-acetylation
38
Caspofungin ADR
GIT, fever, chills, rashes, skin flushing | thrombocytopenia
39
Name the Triazoles
Fluconazole Itraconazole Voriconazole
40
What are the 2 different classes of azalea antifungals?
imidazole and triazoles
41
Imidazole are given ______ while triazoles are given ______
topically, systematically
42
Azoles are fungi___
static
43
Azoles MOA
inhibit C-14 alpha-demethylasse, blocking the demethylation of lanosterol to ergosterol inhibition of ergosterol biosynthesis disrupts membrane structure and function and inhibits fungal cell growth
44
Fluconazole administration
oral, IV
45
Fluconazole indications
Candidemia and most forms of mucocutaneous candidiasis cryptococcal meningitis histoplasmosis blastomycosis single dose for vulvovaginal candidiasis fungal meningitis
46
Fluconazole CSF?
yes
47
Fluconazole cross into breast milk?
yes
48
Fluconazole clearance
renal
49
Fluconazole ADR
``` N/V headache skin ashes hepatotoxicity QT prolongation ```
50
Itraconazole administration
oral | oral solution on empty stomach
51
Itraconazole advantage
broad spectrum
52
Itraconazole indications
blastomycosis and aspergillosis in patients intolerant to Amphotericin B onychomycosis in non immunocompromised patients
53
Itraconazole CSF?
no
54
absorption of Itraconazole decreased with.....
antacids and ppi
55
Itraconazole metabolised in...
liver
56
Itraconazole excreted in...
feces and urine
57
Itraconazole ADR
N/V, HA, skin rashes Hepatotoxicity QT prolongation Itraconazole is associated with cardio toxicity
58
Voriconazole ADR
N/V, HA, skin rashes Hepatotoxicity QT prolongation Neuro toxicity (visual disturbances)
59
Voriconazole administration
oral, IV
60
Voriconazole indications
invasive asperigillosis | candida
61
Voriconazole CSF?
yes
62
Voriconazole metabolism
CYP450
63
Voriconazole elimination
80% of inactive metabolites are exerted via urine
64
What does imidazole have activity against
``` epidermophyton microsporum Trichophyton Candida Malassezia ```
65
Name the 2 imidazole
Clotrimazole | Miconazole
66
Imidazole ADR
Contact dermatitis, vulvar irritation and edema
67
Clotrimazole administration
topical
68
Clotrimazole;s therapeutic uses
dermatophyte infections | vulvovaginal candidiasis
69
Miconazole administration
topical
70
Miconazole persists in skin for ____ days after application
>4
71
Miconazole Indications
tinea pedis, tinea curries and tineaa versicoloured | vulvovaginal candidiasis
72
Imidazole ADR
topical: contact dermatitis, vulvar irritation and deem | GI (for oral admin)
73
What is nystatin?
polyene anti fungal
74
Nystatin MOA
similar to amphotericin B binds to ergosterol in plasma membranes of sensitive fungal cells to forms pores --> disrupt membrane function, allowing electrolytes and small molecules to leak from the cell, resulting in cell death
75
Nystatin administration
oral, cream, pessary
76
Nystatin can be administered as an oral agent for the treatment of.....
oropharyngeal candidiasis
77
is Nystatin used parenterally?
no | systemic toxicity
78
Nystatin spectrum
broad oral or gi vulvovaginal candidiasis
79
What is Nystatin commonly used for
cutaneous and oral candida infections
80
Nystatin ADR
rare. may cause skin irritation
81
Name a squalene epoxidase inhibitor
terbinafine
82
Terbinafine MOA
inhibiting squalene epoxidase --> block its conversion to lanosterol and biosynthesis of ergosterol increased membrane perm and death of the fungal cell
83
Terbinafine Administration
oral and topical
84
Terbinafine is active against
richophyton
85
oral Terbinafine is used to treat
dermatophyte onychomycoses and tinea capitis
86
Terbinafine oral bioavailability
40%
87
Terbinafine (oral) is extensively metabolised by _________ enzymes and excreted mainly via _____
CYP450, urine
88
Terbinafine ADR
GI, HA, rash hepatic failure exacerbation of SLE
89
Terbinafine preggo
cat B (oral) cat A (vaginal)
90
Terbinafine breastfeeding
no

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