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Anti-fungal Flashcards

1
Q

what’s the difference between fungi and mammalian cells?

A

ergosterol cholesterol

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2
Q

what’s the difference between fungi and bacterial cells?

A

fungi: cell wall made of chitin
bacteria: cell made of peptidoglycan

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3
Q

can we use Abx to treat fungal infection?

A

No, vice versa (anti-fungal agents cannot be used to treat bacterial infection)

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4
Q

What are polyenes?

A

Amphotericin B and Nystatin

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5
Q

What are azoles?

A

SC/systemic infection: Triazole

Topical/Cutaneous: Imidazoles

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6
Q

What are echinocandins?

A

Caspofungin, Micafungin, Anidulafungin

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7
Q

Mechanism of action of polyenes?

A

binds to ergosterol in the cell membrane to form pores. Pores allow electrolytes (K) and small molecules to leak from the cell -> causing cell death

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8
Q

Amphotericin B indication?

A

Candida Albicans (Candidiasis), Histoplasmosis, Cryptococcus neoformans (Cryptococcus meningitis), Aspergillus (Aspergillosis)

an be fungicidal or fungistatic depending on organism and conc of drug

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9
Q

Formulation of Amphotericin; Adv/Disadv of each formulation

A

(1) sodium deoxycholate (conventional)
(2) artificial lipids forming liposome

(2) much more expensive than (1)
but (2) has reduced renal toxicity

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10
Q

dosage form/administration of Amphotericin B?

A

Mostly IV, sometimes topical

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11
Q

bioavailability and penetration to CSF for amphotericin B?

A

Poor oral f, poor CSF penetration but increases with inflammation
Liposomal have better CSF penetration

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12
Q

excretion of amphotericin B?

A

urine and bile

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13
Q

Adverse effect of amphotericin B?

A
  • NO (nephro and ototoxicity)
  • nephro = renal vasoconstriction by sodium deoxycholate formulation; avoid adding other nephrotoxic agents (e.g. vancomycin & AG), Hydrate patients adequately
  • bone marrow suppression
  • thrombophlebitis
  • hypotension (accompanied by hypokalemia)
  • fever & chills: 1-3hours after IV but subsides with repeated administration
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14
Q

preg cat for amphotericin B

A

B, safe to use in preg

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15
Q

Imidazoles have a wide range of activity against which fungi?

A
  1. Epidermophyton
  2. Microsporum
  3. Trichophyton
  4. Candida
  5. Malassezia
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16
Q

Topical imidazoles indications? Used for which type of fungal infections?

A 
Tinea corporis
Tinea cruris
Tinea pedia
Oropharyngeal 
Vulvovaginal candidiasis
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17
Q

Adv effects of topical imidazoles?

A

Contact dermatitis
Vulvar irritation and
oedema

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18
Q

What are 3 common tinea infections? (there are 8)

A
  1. Tinea capitis affects the scalp
  2. Tinea corporis affects the arms, legs, trunk
  3. Tinea pedis: athlete’s foot
  4. Tinea manuum: hands and palm
  5. Tinea faciei: face
  6. Tinea barbae: facial hair
  7. Tinea cruris: jock itch
  8. Tinea unguium: fingernails and toe nails
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19
Q

Clotrimazole metabolism and excretion?

A

Metabolised in liver and excreted in bile

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20
Q

Therapeutic uses of Clotrimazole

A
  • dures dermatophyte infections

- vulvovaginal candidiasis

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21
Q

Clotrimazole administration

A

cream (common), lotion, powder, pessary, troche

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22
Q

PK of miconazole

A

penetrates into stratum corneum of skin and persists there for >4days after application

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23
Q

Therapeutic uses of Miconazole

A
  • tinea pedia
  • tinea versicolor
  • vulvovaginal candidiasis
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24
Q

Administration of Miconazole

A

Pessary (common), cream, lotion, powder, oral gel

25
Q

mechanism of action of 5-FC

A

enters fungal cells through cytosine specific permeases, converted by cytosine deaminase to 5-fluorouracil (5-FU); inhibit protein synthesis (FUTP replacing uridylic acid) AND
inhibitor of thymidylate synthase, inhibiting DNA synthesis

26
Q

how does resistance to 5-FC occur?

A
  • decreased levels of any enzymes in conversion of 5-FC to 5-FU
27
Q

Therapeutics uses of Nystatin

A

Broad-spectrum

Thrush oropharyngeal candidiasis and vulvovaginal candidiasis

28
Q

excretion of 5-FC

A

urine, thus need dose adjustment with compromised renal function

29
Q

indication of echinocandins?

A

first line: invasive candidiasis

second line: invasive aspergillosis (cant tolerate Amp B or azole)

30
Q

excretion of echinocandins?

A

urine and faeces; but they are non-renally cleared drugs, so doesnt require dosage adjustment in presence of renal impairment

31
Q

Bioavailability of Terbinafine?

A

40-60%; want the drug to accumulate in the keratin

32
Q

Adverse effects of imidazoles

A 
contact dermatitis
vulvar irritation
oedema
GI disturbances (oral)
oral use of clotrimazole associated with elevated liver enzymes
33
Q

Nystatin falls under which antifungal category?

A

Polyene, like Amp B

34
Q

Therapeutics uses of Nystatin

A

Thrush oropharyngeal candidiasis and vulvovaginal candidiasis

35
Q

Anti-fungal activity of Terbinafine

A

active against trichophyton; a fungi that causes tinea

36
Q

What is the adm of terbinafine for tinea capitis?

A

Oral, not topical antifungal therapy

37
Q

Topical terbinafine is used to treat what kind of tinea?

A

Tinea pedis, Tinea corporis (ring worm), tinea cruris (infection of groin)

38
Q

Bioavailability of nystatin

A

Poor F, systemic toxicity when used parenterally

39
Q

Metabolism of oral terbinafine?

A

CYP450 isoenzymes

40
Q

Pregnancy category for vaginal terbinafine

A

A

41
Q

Pregnancy category for oral terbinafine

A

B

42
Q

DDI of terbinafine

A

Terbinafine is an inhibitor of CYP450 isoenzymes

43
Q

Adv effects of Terbinafine

A

GI disturbances
HA
rash
elevated liver enzymes

44
Q

Excretion of oral terbinafine

A

mainly via urine; avoided in pts w moderate to severe renal impairment or hepatic dysfunction

45
Q

Oral F of nystatin

A

Poor F, systemic toxicity

46
Q

DDI of azoles

A

inhibit the hepatic cyp450 3a4 enzyme, cyp2c9, cyp2c19 -> enhance activity of warfarin, cyclosporine, oral hypolycaemic agent

47
Q

clearance of triazole

A

renal; dose adjustment needed in renal and hepatic impairment (due to DDI)

48
Q

preg cat for triazole

A

flucanzole, itraconazole = cat C
voriconazole = cat D
Azoles are considered teratogenic

49
Q

Bioavailability of Imidazoles

A

Poor F

50
Q

how does resistance of azole come about?

A
  • mutation in C14a-demethylase

- efflux pumps

51
Q

PK of nystatin

A

Not abs from GIT, skin or vagina

52
Q

Adv effects of nystatin

A

oral: rare

topical & vaginal forms: skin irritation

53
Q

usual use of triazole (indication); name each and its indication

A

fluconazole = cryptococcal meningitis, vulvovaginal candidiasis

itraconazole = aspergillosis, onychomycosis, broader antifungal spectrum than fluconazole

voriconazole = treatment of choice for invasive asperigillosis

54
Q

names of the triazoles

A

fluconazole, itraconazole, voriconazole

55
Q

which anti-fungal; capsule to be taken after meal but solution on an empty stomach

A

itraconazole

56
Q

which 2 azoles can be used to treat invasive aspergillosis and cryptococcal meningitis respectively? and what is the reason

A

voriconazole, fluconazole, both have good CSF penetration

57
Q

which group of people is terbinafine contraindicated?

A

nursing mothers; distribute into milk

58
Q

adverse effect of echinocandins?

A

GI effects, thrombocytopenia, fever & chills, rash, skin flush

PT (19 decks)

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