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PHARM 2 > anti-fungals > Flashcards

anti-fungals Flashcards

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
Q

DOC for coccidiomycosis

A

fluconazole

26
Q

DOC for consolidation and maintenance therapy of cryptococcal meningitis after induction with amphotericin B

A

fluconazole

27
Q

amphotericin B alternative for non severe cryptococcal meningitis

A

fluconazole

28
Q

DOc for inital and secondary prophylaxis against cryptococcal meningitis

A

fluconazole

29
Q

fluconazole is ineffective against

A

aspergillus

filamentous fungi

30
Q

itraconazole

A

metabolized by CYP3A4
inhibits CYP3A4 - fatal arrythmias when given with cisapride or quinidine

absorption reduced by antacids, H2 blockers, PPI

poor CSF penetration

31
Q

itraconazole use

A

dimorphic fungi:
blastomyces
sporothrix
histoplasma

aspergillus - (replaced by voriconazole)

used for dermatophytoses and ocychomycosis

32
Q

DOC invasive aspergillus

A

voriconzale

33
Q

voriconazole AE

A

visual disturbances

metabolized by CYP2C19, CYP2C9 and CYP3A4

34
Q

posaconazole

A

active against zygomyctes - like mucor

inhibtis CYP3A4

similar spectrum to itraconazole

35
Q

echinocandins - caspofungin

A

large cyclic peptides - linked to long chain FA

active against candida, aspergillus - NOT cryptoccocus

only IV

36
Q

enchinocandins: caspofungin MOA

A

inhibit synthesis of beta(1-3)-d-glucans in fungal cell wall

disrupts fungal cell wall and cell death

37
Q

systemic drugs for superficial mycoses

A 
grisefulvin
terbinafine
ketoconazole
fluconazole
itraconazole
38
Q

griseofulvin

A

tx dermatophytosis

inc absorption with fatty foods

MOA: disrupts mitotic spindle - inhibits mitosis

39
Q

griseofulvin use

A

dermatophytoses of skin, hair, nails

now replaced by itraconazole and terbinafine

indcues P450 enzymes (can increase metabolism of drugs like warfarin)

40
Q

terbinafine

A

allylamine - oral admin

41
Q

terbinafine MOA

A

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
Q

terbinafine AE

A

no P450 metabolism - no drug interactions

Gi upset

43
Q

oral tx of dermatophytoses

A

ketoconazole
fluconzole
itraconazole

44
Q

topicals for superficial mycoses

A 
nystatin
amphotericin B
clotrimazole
miconazole
ketoconazole
terbinafine
45
Q

nystatin

A

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
Q

amphotericin topical use

A

cutaneous candidiasis

47
Q

most commonly used topical azoles

A

clotrimazole
miconazole

most over the counter

48
Q

DOC tinea cruris and tinea corporis topicals

A

terbinafine

49
Q

DOC mild oropharyngeal candidiasis

A

topical clotrimazole or nystatin

50
Q

DOC moderate to severe oropharyngeal candidiasis

A

oral fluconazole

51
Q

AIDS pt with oropharyngeal candidiasis DOC

A

oral fluconazole

52
Q

reccurent vulvovaginal candiasis DOC

A

oral fluconazole

53
Q

vulvovaginal candiasis DOC

A

topical azoles

54
Q

candidemia DOC

A

IV fluconazole OR IV echinocandin

55
Q

cryptococcus DOC

A

amphotericin B + oral flucytosine then oral fluconazole

56
Q

invasive aspiergillosis DOC

A

IV and then oral voriconazole

57
Q

mucormycosis DOC

A

amphotericin B

58
Q

fusariosis DOC

A

amphotericin B

59
Q

onchymycosis DOC

A

oral terbinaine OR oral itraconazole OR oral fluconazole

60
Q

DOC PCP

A

co-trimoxazole

61
Q

DOC prophylaxis of PCP in immunocompromised

A

co-trimoxazole

62
Q

PCP alternative therapies

A

clindamycin + primaquine

dapsone + trimethoprim

atovaquone

pentamidine

if mod-severe, should also be given prednisone

PHARM 2 (18 decks)

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