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PR3124 CA1 > Lecture 4- antifungal agents > Flashcards

Lecture 4- antifungal agents Flashcards

1
Q

what does fungal cell membrane contain?

A

ergosterol instead of cholesterol

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2
Q

2 broad categories of antifungal drug

A
  1. drug for subcutaneous and systemic mycotic infections

2. drugs for cutaneous mycotic infection

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3
Q

what are the classes of antifungal drugs (3)

A
  1. polyenes
  2. azoles
  3. achinocandins
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4
Q

how do polyenes work?

A

bind to ergosterol and cause pores to develop in cell membrane

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5
Q

how do azoles work

A

inhibits lanosterol 14 alphs demethylase and inhibits ergosterol synthesis

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6
Q

echinocandins MOA

A

inhibits beta 1,3- glucan synthase

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7
Q

types of polyenes? (2)

A
  1. amphotericin B

2. nystatin

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8
Q

amphotericin B MOA

A

bind to ergosterol in plasma membrane –> form pores–> pores disrupt membrane func–> allow electrolytes to leak out–> cell death

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9
Q

amphotericin B spectrum

A

fungicidal

wide coverage

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10
Q

amphotericin B indication

A

against oral candidiasis

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11
Q

amphotericin B ROA

A

topical, slow IV

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12
Q

amphotericin B absorption

A

poor csf penetration

extensively bound to plasma protein

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13
Q

amphotericin B excretion

A

urine, bilé

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14
Q

amphotericin B adverse

A

fever and chills, nephrotoxicity

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15
Q

amphotericin B CI

A

renal impairment

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16
Q

amphotericin B preg

A

cat B

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17
Q

5-flucytosine MOA

A
  • convert 5FU to 5-fluorouridine triphosphate (FUTP) FUTP then inhibits protein synthesis
  • 5FU metabolised into FdUMP– inhibits DNA synthesis
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18
Q

5-flucytosine spectrum

A

fungistatic

used in combi with other drugs eg. ampho B to treat candidiasis

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19
Q

5-flucytosine absorption and ROA

A

absorbed well by oral route
penetrates well into CSF
dose adjusted inrenal impari

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20
Q

5-flucytosine adverse

A

GI, bone marrow suppression- need to monitor leucocytes and platelets, hepatotox

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21
Q

5-flucytosine resistance

A

can be due to decreased level of any eznyesm inthe conversion of 5FC to its metabolites
very susceptible to resisitance– usually dont use alone

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22
Q

types of echinocandins (3)

A
  1. caspofungin
  2. micofungin
  3. anidulafungin
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23
Q

echinocandins MOA

A

inhibit activity of glucan synthase complex–> loss of structural integrity of cell wall

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24
Q

echinocandins properties

A
  • lack oral bioavail
  • extensive protein binding
  • cannot penetrate CSF
  • broad specturm activity
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25
Q

caspofungin ROA

A

IV

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26
Q

caspofungin use

A

first line for invasive candidiasis

second line for invasive aspergillosis

27
Q

caspofungin elim

A

in urine and faces
no need dose adjustment
not met by cyp450 enzymes

28
Q

caspofungin adverse

A

GIT, fever, chills, rashes

29
Q

classes of azole antifungals (2)

A
  1. imidazole

2. triazoles

30
Q

azole MOA

A

inihibit c14 alpha demethylase (CYP450) enzymes–> block demethylation –> disrupts membrane structure and func–> inhibit fungal cell growth

31
Q

triazoles ROA and use

A

systemically

treat cutaneous and systemic fungal infection

32
Q

types of triazoles (3)

A
  1. fluconazole
  2. itraconazole
  3. voriconazole
33
Q

fluconazole ROA

A

oral, iv

34
Q

fluconazole uses

A
  • treat candidemia, cryptococcal meningitis, vulvovaginal candidiasis single dose oral tx
35
Q

itraconazole roa

A

oral apsules taken after full meal
oral soln on empty stomach
poor csf penetration due to larger size

36
Q

itroconazole indications

A

braod antifungal spectrum

treat blastomycosis and aspergillosis

37
Q

itraconazole excretion

A

met by live, excreted in urine and faeces

38
Q

voriconazole ora

A

oral, iv

39
Q

voriconazole indicationa

A

braod spectrum antifungal agent

treat invasive aspergillosis and candida infections

40
Q

voriconazole distri

A

high oral bioavail

good csf penetration

41
Q

itraconazole adverse

A

cardiotoxicity

42
Q

voriconazole adverse

A

neurotoxicity

43
Q

triazoles adverse

A

QT prolongation, rash, nausea, hepatotoxicity

44
Q

triazoles resistnace

A

mutation in c14 alpha demethylase gene–> decrease azole binding

45
Q

triazoles pregnancy

A

avoided
fluco and itra cat C
vori cat d

46
Q

classes of antifungals used to treat SUBCUTANEOUS AND SYSTEMIC infection

A
  1. ampho B
  2. 5-flucytosine
  3. echonicandins
  4. triazoles
47
Q

types of imidazoles (2)

A
  • clotrimazole

- . miconazole

48
Q

imidazoles roa

A

topical

49
Q

imidazoles uses

A

tinea corposis, tinea cruris, tinea pedis…

50
Q

imidazoles adverse

A

contact dermititis, edema

51
Q

clotrimazole uses

A
  • dermatophyte infections

- vulvovaginal candidiasis

52
Q

miconazole uses

A

treat tinea pedis, tinea cruris, vulvovaginal candidiasis

53
Q

miconazole abdosprtion

A

penetrates skin well but does not get absorbed into blood

54
Q

miconazole adverse

A

contact dermititis, vulvar irritation, edema

gi disturbances

55
Q

what class is nystatin?

A

polyene antifungal

56
Q

nystatin roa

A

oral, cream , pessary

NOT used parentareally due to systemic tox

57
Q

nystatin use

A

broad spec
treat oral or GI fungal infections and vulvovaginal candidiasis
for cutaneous and oral candida infections

58
Q

terbinafine moa

A

inhibit squalene epoxidase
increase membrane permeability
death of fungal cell

59
Q

terbinafine roa

A

oral, topical

60
Q

terbinafine uses

A

oral: treat dermatophyte onychomycoses (nail) and tinea capitis (scalp)
topical: ringworm

61
Q

terbinafine ci

A

avoid in pt with renal impari or hepatic dysfunc

- oral avoided during breastfeeding

62
Q

terbinafine in preg

A

cat A- vaginal

cat b- oral

63
Q

cutaneous antifungals (3)

A
  1. imidazoles (clot and mico)
  2. nystatin
  3. terbinafine

PR3124 CA1 (5 decks)

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