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PHARM 2 > anti-fungals > Flashcards

anti-fungals Flashcards

(62 cards)

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1
Q

drugs used for subcutaneous and systemic mycoses (SEVERE INFEC)

A

amphotericin B
flucytosine
azoles
echinocandins

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2
Q

amphotericin B

A

polyene - fungicidal

binds ergosterol - forms pores in cell membranes

leakage of intracellular ions and macromolecules = cell death

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3
Q

antifungal with broadest spectrum

A

amphotericin B

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4
Q

amphotericin B administration

A

IV (poor GI absorption)

low CSF penetration - intrathecal therapy for meningeal dz

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5
Q

initial induction tx to rapidly reduce fungal burden

A

amphotericin B

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6
Q

amphotericin AE

A

infusion related toxicity - muscle spasms. fever/chills. hypotension. attenuate by dec influsion rate or decreasing daily dose (occurs as pt is receiving infusion)
pre-medication with antihistamines, glucocorticoids, antipyretics, meperidine to minimize AE

Slower toxicity:
binds cholesterol and forms pores in mammalian cell membranes = renal toxicity

renal impairment and azotemia - in almost all pt
dec GFR
renal tubular acidosis - Mg and K wasting
attenuate renal damage with Sodium loading

LFTs
hypochromic normocytic anemia

seizures - d/t intrathecal administration

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7
Q

preferred tx for deep fungal infections during pregnancy

A

amphotericin

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8
Q

what is amphotericin usually administered with

A

IV saline (sodium)- to reduce renal damage

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9
Q

what is recommended to monitor with pt taking amphotericin

A 
renal function
liver function
serum electrolytes (Mg and K)
blood counts
Hgb
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10
Q

amphotericin B lipid formulations

A

reduce nephrotoxicity - reduces exposure to nephron

1) liposomal amphotericin B
2) amphotericin B lipid complex
3) amphotericin B colloidal dispersion

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11
Q

Flucytosine

A

synthetic pyrimidine antimetabolite

taken by fungal cells via cytosine permease - converted intracellularly to 5’FU - 5-FdUMP = inhibits thymidylate synthetase = blocking dTMP synthesis

5-FUTP = inhibits protein synthesis

mammalian cells don’t have enzyme, can’t convert parent drug to active metabolite

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12
Q

flucytosine + ______ gives synergistic effect

A

flucytosine + amphotericin B

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13
Q

when to use flyucytosine

A

in serious infections by candida and/or cryptococcus

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14
Q

Flucytosine AE

A

result of 5’FU

BM toxicity

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15
Q

Azoles

A

imidazoles and triazoles

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16
Q

imidazoles

A

ketoconazole
miconazole
clotrimazole

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17
Q

triazoles

A

itraconazole
fluconazole
voriconazole
posaconazole

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18
Q

azoles MOA

A

14-alpha demethylase = catalyses conversion of lanosterol to ergosterol - inhibits enzyme

makes membrane leaky, inc permeability

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19
Q

azoles AE

A

minor GI upset

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20
Q

Ketoconazole

A

inhibits mammalian P450

can dec testosterone as a consequence = gynecomastia, dec libido, dec potency in men

high doses may inhibit steroid synth and dec cortisol elvels

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21
Q

ketoconazole use

A

rarely used for systemic b/c of AE. used for superficial

CYP3A4 inhibitor = potentiate toxicities of warfarin, cyclopsorine etc

best absorbed at low pH (antacids, H2 blockers, PPIs interfere)

poor penetration in CSF

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22
Q

fluconazole

A

oral/IV
moderate inhibitor of CYP3A4
strong inhibitor of CYP2C9 = can inc levels of phenytoin, zidovudine, warfarin

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23
Q

DOC in esophageal/oropharyngeal, vulvovaginal, urianry candidiasis

A

fluconazole

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24
Q

DOC for candidemia

A

fluconazole

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25
DOC for coccidiomycosis
fluconazole
26
DOC for consolidation and maintenance therapy of cryptococcal meningitis after induction with amphotericin B
fluconazole
27
amphotericin B alternative for non severe cryptococcal meningitis
fluconazole
28
DOc for inital and secondary prophylaxis against cryptococcal meningitis
fluconazole
29
fluconazole is ineffective against
aspergillus | filamentous fungi
30
itraconazole
metabolized by CYP3A4 inhibits CYP3A4 - fatal arrythmias when given with cisapride or quinidine absorption reduced by antacids, H2 blockers, PPI poor CSF penetration
31
itraconazole use
dimorphic fungi: blastomyces sporothrix histoplasma aspergillus - (replaced by voriconazole) used for dermatophytoses and ocychomycosis
32
DOC invasive aspergillus
voriconzale
33
voriconazole AE
visual disturbances | metabolized by CYP2C19, CYP2C9 and CYP3A4
34
posaconazole
active against zygomyctes - like mucor inhibtis CYP3A4 similar spectrum to itraconazole
35
echinocandins - caspofungin
large cyclic peptides - linked to long chain FA active against candida, aspergillus - NOT cryptoccocus only IV
36
enchinocandins: caspofungin MOA
inhibit synthesis of beta(1-3)-d-glucans in fungal cell wall disrupts fungal cell wall and cell death
37
systemic drugs for superficial mycoses
``` grisefulvin terbinafine ketoconazole fluconazole itraconazole ```
38
griseofulvin
tx dermatophytosis inc absorption with fatty foods MOA: disrupts mitotic spindle - inhibits mitosis
39
griseofulvin use
dermatophytoses of skin, hair, nails now replaced by itraconazole and terbinafine indcues P450 enzymes (can increase metabolism of drugs like warfarin)
40
terbinafine
allylamine - oral admin
41
terbinafine MOA
inhibits squalene epoxidase = prevents ergosterol synthesis accumulates toxic levels of squalene in fungal cell = accumualtes in keratin (much more effective in onychomycosis than griseofulvin)
42
terbinafine AE
no P450 metabolism - no drug interactions Gi upset
43
oral tx of dermatophytoses
ketoconazole fluconzole itraconazole
44
topicals for superficial mycoses
``` nystatin amphotericin B clotrimazole miconazole ketoconazole terbinafine ```
45
nystatin
polyene macrolide same mechanism as amphotericin B too toxic for IV only used for candidiasis not absorbed in GIT, skin, vagina = therefore not really toxic
46
amphotericin topical use
cutaneous candidiasis
47
most commonly used topical azoles
clotrimazole miconazole most over the counter
48
DOC tinea cruris and tinea corporis topicals
terbinafine
49
DOC mild oropharyngeal candidiasis
topical clotrimazole or nystatin
50
DOC moderate to severe oropharyngeal candidiasis
oral fluconazole
51
AIDS pt with oropharyngeal candidiasis DOC
oral fluconazole
52
reccurent vulvovaginal candiasis DOC
oral fluconazole
53
vulvovaginal candiasis DOC
topical azoles
54
candidemia DOC
IV fluconazole OR IV echinocandin
55
cryptococcus DOC
amphotericin B + oral flucytosine then oral fluconazole
56
invasive aspiergillosis DOC
IV and then oral voriconazole
57
mucormycosis DOC
amphotericin B
58
fusariosis DOC
amphotericin B
59
onchymycosis DOC
oral terbinaine OR oral itraconazole OR oral fluconazole
60
DOC PCP
co-trimoxazole
61
DOC prophylaxis of PCP in immunocompromised
co-trimoxazole
62
PCP alternative therapies
clindamycin + primaquine dapsone + trimethoprim atovaquone pentamidine if mod-severe, should also be given prednisone

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